Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. This is an updated version of the original review published in 2003.
To assess the effects of treatments for impetigo, including non-pharmacological interventions and 'waiting for natural resolution'.
We updated our searches of the following databases to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials, and we handsearched the reference lists of new studies found in the updated search.
Randomised controlled trials of treatments for non-bullous, bullous, primary, and secondary impetigo.
Two independent authors undertook all steps in data collection. We performed quality assessments and data collection in two separate stages.
We included 57 trials in the first version of this review. For this update 1 of those trials was excluded and 12 new trials were added. The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments, including placebo. Most trials were in primary impetigo or did not specify this.
For many of the items that were assessed for risk of bias, most studies did not provide enough information. Fifteen studies reported blinding of participants and outcome assessors.
Topical antibiotic treatment showed better cure rates than placebo (pooled risk ratio (RR) 2. 24, 95% confidence interval (CI) 1.61 to 3.13) in 6 studies with 575 participants. In 4 studies with 440 participants, there was no clear evidence that either of the most commonly studied topical antibiotics (mupirocin and fusidic acid) was more effective than the other (RR 1.03, 95% CI 0.95 to 1.11).
In 10 studies with 581 participants, topical mupirocin was shown to be slightly superior to oral erythromycin (pooled RR 1.07, 95% CI 1.01 to 1.13). There were no significant differences in cure rates from treatment with topical versus other oral antibiotics. There were, however, differences in the outcome from treatment with different oral antibiotics: penicillin was inferior to erythromycin, in 2 studies with 79 participants (pooled RR 1.29, 95% CI 1.07 to 1.56), and cloxacillin, in 2 studies with 166 participants (pooled RR 1.59, 95% CI 1.21 to 2.08).
There was a lack of evidence for the benefit of using disinfectant solutions. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments (RR 1.15, 95% CI 1.01 to 1.32).
The reported number of side-effects was low, and most of these were mild. Side-effects were more common for oral antibiotic treatment compared to topical treatment. Gastrointestinal effects accounted for most of the difference.
Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.
There is good evidence that topical mupirocin and topical fusidic acid are equally, or more, effective than oral treatment. Due to the lack of studies in people with extensive impetigo, it is unclear if oral antibiotics are superior to topical antibiotics in this group. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. There is a lack of evidence to support disinfection measures to manage impetigo.
Interventions dans l'impétigo
L'impétigo est une infection bactérienne cutanée superficielle courante qui touche généralement les enfants. Il n'existe aucun traitement standard homologué et les recommandations de traitement diffèrent sensiblement. Les options de traitement incluent plusieurs antibiotiques oraux et topiques différents, ainsi que des désinfectants. Ceci est une version mise à jour de la revue originale publiée en 2003.
Évaluer les effets des traitements de l'impétigo, y compris les interventions non pharmacologiques et l'« attente d'une guérison naturelle ».
Nous avons mis à jour nos recherches portant sur les bases de données suivantes jusqu'à juillet 2010 : le registre spécialisé du groupe Cochrane sur la dermatologie, le registre Cochrane des essais contrôlés (CENTRAL), MEDLINE (à partir de 2005), EMBASE (à partir de 2007) et LILACS (à partir de 1982). Nous avons également effectué des recherches en ligne dans les registres d'essais pour les essais en cours, ainsi que des recherches manuelles dans les listes bibliographiques des nouvelles études identifiées dans la recherche mise à jour.
Des essais contrôlés randomisés portant sur le traitement de l'impétigo non bulleux, bulleux, primaire et secondaire.
Deux auteurs ont suivi toutes les étapes de collecte de données de façon indépendante. Nous avons procédé à des évaluations de la qualité et à la collecte de données dans deux étapes différentes.
Nous avons inclus 57 essais dans la première version de cette revue. Pour cette mise à jour, 1 de ces essais a été exclu et 12 nouveaux essais ont été ajoutés. Le nombre total d'essais inclus était donc de 68, avec un total de 5 578 participants, présentant 50 traitements différents, y compris un placebo. La majorité des essais portaient sur l'impétigo primaire ou ne le mentionnaient pas.
Pour plusieurs des éléments dont les risques de biais étaient évalués, la majorité des études fournissaient des informations insuffisantes. Quinze études indiquaient une mise en aveugle des participants et des évaluateurs de résultats.
Un traitement à base d'antibiotiques topiques révélait de meilleurs taux de guérison par rapport à un placebo (risque relatif (RR) groupé 2,24, intervalle de confiance (IC) à 95 % 1,61 à 3,13) dans 6 études de 575 participants. Dans 4 études de 440 participants, aucune preuve probante ne révélait que l'un des antibiotiques topiques les plus couramment étudiés (la mupirocine et l'acide fusidique) était plus efficace qu'un autre (RR 1,03, IC à 95 % 0,95 à 1,11).
Dans 10 études de 581 participants, la mupirocine topique était légèrement supérieure à l'érythromycine orale (RR groupé 1,07, IC à 95 % 1,01 à 1,13). Aucune différence significative n'a été constatée au niveau des taux de guérison à l'issue du traitement à base d'antibiotiques topiques par rapport à d'autres antibiotiques oraux. Toutefois, des différences de résultats au niveau du traitement à base de plusieurs antibiotiques oraux ont été constatées : la pénicilline était inférieure à l'érythromycine, dans deux études de 79 participants (RR groupé 1,29, IC à 95 % 1,07 à 1,56) et la cloxacilline, dans 2 études de 166 participants (RR groupé 1,59, IC à 95 % 1,21 à 2,08).
Les preuves étaient insuffisantes concernant les effets bénéfiques liés à des solutions désinfectantes. Lors du regroupement de 2 études composées de 292 participants, les antibiotiques topiques se sont révélés beaucoup plus efficaces que les traitements désinfectants (RR 1,15, IC à 95 % 1,01 à 1,32).
Le nombres d'effets secondaires signalés étaient faibles et la majorité d'entre eux étaient légers. Des effets secondaires étaient plus courants dans le cas d'un traitement à base d'antibiotiques oraux par rapport à un traitement topique. Les effets gastro-intestinaux étaient majoritaires.
Partout dans le monde, les bactéries à l'origine de l'impétigo sont de plus en plus résistantes aux antibiotiques couramment prescrits. Dans le cas d'un traitement topique récemment mis au point, la rétapamuline, aucune résistance n'a encore été signalée.
Il existe des preuves probantes selon lesquelles la mupirocine et l'acide fusidique topique sont pareillement, voire plus, efficaces qu'un traitement oral. En raison du manque d'études concernant les personnes souffrant d'un impétigo étendu, la supériorité des antibiotiques oraux par rapport aux antibiotiques topiques reste à déterminer dans ce groupe. L'efficacité de l'acide fusidique et de la mupirocine est similaire. La pénicilline n'était pas aussi efficace que la majorité des autres antibiotiques. Il n'existe pas suffisamment de preuves permettant de corroborer les méthodes de désinfection pour la gestion de l'impétigo.
Interventions for the skin infection impetigo
Impetigo causes blister-like sores. The sores can fill with pus and form scabs, and scratching can spread the infection. Impetigo is caused by bacteria. It is contagious and usually occurs in children. It is the most common bacterial skin infection presented by children to primary care physicians. Treatment options include topical antibiotics (antibiotic creams), oral antibiotics (antibiotics taken by mouth), and disinfectant solutions. There is no generally agreed standard treatment, and the evidence on what intervention works best is not clear.
We identified 68 randomised controlled trials comparing various treatments for impetigo. Altogether, these studies evaluated 26 oral treatments and 24 topical treatments, including placebo, and results were described for 5708 participants.
Overall, topical antibiotics showed better cure rates than topical placebo.
Two antibiotic creams, mupirocin and fusidic acid, are at least as effective as oral antibiotics where the disease is not extensive. There was no clear evidence that either of these most commonly studied topical antibiotics was more effective than the other.
Topical mupirocin was superior to the oral antibiotic, oral erythromycin.
We found that the oral antibiotic, oral penicillin, is not effective for impetigo, while other oral antibiotics (e.g. erythromycin and cloxacillin) can help.
It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo.
There is a lack of evidence to suggest that using disinfectant solutions improves impetigo. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments.
Reported side-effects for topical treatments were mild and low in frequency; the treatments sometimes resulted in itching, burning, or staining. Oral antibiotics produced gastrointestinal complaints, such as nausea and diarrhoea, in 2% to 30% of participants, depending upon the specific antibiotic.
Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.
Interventions dans l'impétigo (infection cutanée)
L'impétigo provoque des plaies semblables à des cloques. Ces plaies peuvent contenir du pus et former des croûtes et le fait de se gratter entraîne la propagation de l'infection. Des bactéries sont à l'origine de l'apparition de l'impétigo. Il est particulièrement contagieux et touche généralement les enfants. Il s'agit de l'infection bactérienne cutanée la plus couramment diagnostiquée chez les enfants par les médecins généralistes. Les options de traitement incluent des antibiotiques topiques (crèmes antibiotiques), des antibiotiques oraux (antibiotiques avalés par la bouche) et des solutions désinfectantes. En général, il n'existe aucun traitement standard homologué et aucune preuve relative à l'intervention la plus efficace n'a été établie avec certitude.
Nous avons identifié 68 essais contrôlés randomisés comparant plusieurs traitements de l'impétigo. Toutes ces études ont évalué 26 traitements oraux et 24 traitements topiques, y compris un placebo, et les résultats concernant 5 708 participants ont été examinés.
Dans l'ensemble, les antibiotiques topiques ont affichés de meilleurs taux de guérison qu'un placebo topique.
Deux crèmes antibiotiques, la mupirocine et l'acide fusidique, sont au moins aussi efficaces que les antibiotiques oraux en cas de maladie bénigne. Aucune preuve claire n'a permis de démontrer que l'un de ces antibiotiques topiques les plus couramment étudiés était plus efficace qu'un autre.
La mupirocine était plus efficace qu'un antibiotique oral, l'érythromycine orale.
Nous avons trouvé qu'un antibiotique oral, la pénicilline orale, est inefficace pour le traitement de l'impétigo, contrairement à d'autres antibiotiques oraux qui pourraient aider (par ex. : l'érythromycine et la cloxacilline).
On ignore si les antibiotiques oraux sont supérieurs aux antibiotiques topiques chez les personnes souffrant d'un impétigo sévère.
Les preuves sont insuffisantes pour démontrer que les solutions désinfectantes atténue l'impétigo. Lors du regroupement de 2 études composées de 292 participants, les antibiotiques topiques se sont révélés beaucoup plus efficaces que les traitements désinfectants.
La fréquence des effets secondaires signalés pour les traitements topiques était légère et faible ; les traitements provoquaient parfois des démangeaisons, des brûlures ou des tâches. Les antibiotiques oraux entraînaient des maladies gastro-intestinales, comme des nausées et des diarrhées, chez 2 à 30 % des participants en fonction de l'antibiotique spécifique.
Partout dans le monde, les bactéries à l'origine de l'impétigo sont de plus en plus résistantes aux antibiotiques couramment prescrits. Dans le cas d'un traitement topique récemment mis au point, la rétapamuline, aucune résistance n'a encore été signalée.
Notes de traduction
Recherches parrainées
Le parrainage industriel ou l'organisation de l'essai était mentionné(e) dans 20 essais (29 %) : 5 études sur la mupirocine (Goldfarb 1988 ; Mertz 1989 ; Rist 2002 ; Wainscott 1985 ; White 1989), 2 sur le cefdinir (Tack 1997 ; Tack 1998), 2 sur le céfadroxil (Beitner 1996 ; Hains 1989), 2 sur l'azithromycine (Daniel 1991a ; Daniel 1991b), 2 sur le cefditoren (Bucko 2002a ; Bucko 2002b) ; 2 sur la rétapamuline (Koning 2008 ; Oranje 2007) ; 1 sur l'amoxicilline plus l'acide clavulanique (Jaffe 1985), la céfalexine (Dillon 1983 ; Giordano 2006), la clindamycine (Blaszcyk 1998) et l'acide fusidique (Sutton 1992). Cinq essais (9 %) ont été parrainés par d'autres organisations. Pour les 48 essais restants (67 %), aucune déclaration de parrainage ou de financement n'a été indiquée (voir Tableau 2 « Parrainage ou financement déclaré »).
Traduit par: French Cochrane Centre 10th April, 2012
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français
Intervensi untuk jangkitan kulit impetigo.
Impetigo menyebabkan kudis yang berupa lepuh. Kudis boleh mengandungi nanah dan membentuk kuping, dan penggaruan kulit boleh merebakkan jangkitan. Impetigo disebabkan oleh bakteria. Ia mudah berjangkit dan biasanya berlaku pada kanak-kanak. Ia adalah jangkitan kulit bakteria yang paling biasa ditunjukkan oleh kanak-kanak kepada doktor penjagaan utama. Pilihan rawatan termasuk antibiotik topikal (krim antibiotik), antibiotik oral (antibiotik diambil melalui mulut), dan larutan disinfektan. Tiada rawatan standard umum yang disetujui dan bukti mengenai intervensi yang berfungsi tidak jelas.
Kami telah mengenal pasti 68 ujian terkawal rawak yang membandingkan pelbagai rawatan untuk impetigo. Semua kajian ini menilai 26 rawatan oral dan 24 rawatan topikal, termasuk plasebo, dan keputusan telah diperolehi daripada 5708 peserta.
Secara keseluruhannya, antibiotik topikal menunjukkan kadar penyembuhan yang lebih baik daripada plasebo topikal.
Dua krim antibiotik, mupirocin dan asid fusidic, sekurang-kurangnya berkesan sebagai antibiotik oral di mana penyakit ini tidak merebak dengan luas. Tidak ada bukti jelas bahawa salah satu daripada kedua-dua antibiotik topikal paling biasa dikaji adalah lebih berkesan daripada yang lain.
Mupirocin topikal lebih berkesan daripada antibiotik oral, erythromycin oral.
Kami mendapati bahawa antibiotik oral, penicillin oral, tidak berkesan untuk impetigo, manakala antibiotik oral lain (misalnya erythromycin dan cloxacillin) boleh membantu.
Ia adalah tidak jelas samada antibiotik oral adalah lebih berkesan daripada antibiotik topikal untuk orang dengan impetigo yang merebak luas.
Terdapat kekurangan bukti yang menunjukkan bahawa penggunaan larutan disinfektan boleh memulihkan impetigo. Apabila 2 kajian dengan 292 peserta telah dikumpulkan, antibiotik topikal adalah jauh lebih baik daripada rawatan pembasmi kuman.
Kesan sampingan untuk rawatan topikal dilaporkan lebih ringan dan tidak begitu kerap; rawatan kadang-kadang menyebabkan kegatalan, rasa panas atau pengotoran. Antibiotik oral menyebabkan aduan gastrousus seperti loya dan cirit-birit, dalam 2% kepada 30% daripada peserta, bergantung kepada antibiotik tertentu.
Di seluruh dunia, bakteria yang menyebabkan impetigo menunjukkan kadar rintangan yang semakin meningkat untuk antibiotik yang biasa digunakan. Untuk rawatan topikal yang baru digunakan retapamulin, tiada rintangan telah dilaporkan.
Catatan terjemahan
Diterjemahkan oleh Ng Chia Shyn (International Medical University). Disunting oleh Tuan Hairulnizam Tuan Kamauzaman (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan ini sila hubungi Ng.ChiaShyn@student.imu.edu.my.
Impetigo or impetigo contagiosa is a contagious superficial bacterial skin infection most frequently encountered in children. It is typically classified as either primary (e.g. direct bacterial invasion of previously normal skin), secondary, or common impetigo (where the infection is secondary to some other underlying skin disease that disrupts the skin barrier, such as scabies or eczema). Impetigo is also classified as bullous or non-bullous impetigo. Bullous impetigo simply means that the skin eruption is characterised by bullae (blisters). The term 'impetigo contagiosa' is sometimes used to mean non-bullous impetigo, and at other times it is used as a synonym for all impetigo.
Non-bullous impetigo is the most common form of impetigo. The initial lesion is a thin-walled vesicle on previously normal skin that rapidly ruptures. It then leaves superficial erosion covered with yellowish-brown or honey-coloured crusts. The crusts eventually dry, separate, and disappear, leaving a red mark that heals without scarring. The most frequently affected areas are the face and limbs. The lesions are sometimes painful. Usually, there are no systemic symptoms such as fever, malaise, or anorexia. Swelling of the lymph nodes draining the infected area of skin is common. It is believed that, in most cases, spontaneous resolution may be expected within two to three weeks without treatment but more prompt resolution occurs with adequate treatment. Diagnostic confusion can occur with a variety of skin disorders including shingles, cold sores, cutaneous fungal infections, and eczema (Hay 1998; Resnick 2000). Pyoderma is sometimes used as a synonym for impetigo in tropical countries. This is usually to denote streptococcal, as opposed to staphylococcal, impetigo.
Bullous impetigo is characterised by larger bullae or blisters that rupture less readily and can persist for several days. Usually there are fewer lesions and the trunk is affected more frequently than in non-bullous impetigo. Diagnostic confusion can occur with thermal burns, blistering disorders (e.g. bullous pemphigoid), and Stevens Johnson syndrome.
Staphylococcus aureus (S. aureus) is considered to be the main bacterium that causes non-bullous impetigo. However, Streptococcus pyogenes (S. pyogenes), or both S. pyogenes and S. aureus, are sometimes isolated from the skin. In moderate climates, staphylococcal impetigo is more common, whereas in warmer and more humid climates, the streptococcal form predominates. In moderate climates, the relative frequency of S. aureus infections has also changed with time (Dagan 1993). It was predominant in the 1940s and 1950s, after which Group A streptococci became more prevalent. In the past two decades, S. aureus has become more common again. Bullous impetigo is always caused by S. aureus.
Secondary impetigo may occur as a complication of many dermatological conditions (notably eczema). The eruption appears clinically similar to non-bullous impetigo. Usually S. aureus is involved. The underlying skin disease may improve with successful treatment of the impetigo, and the converse may also be true.
Complications of non-bullous impetigo are rare, but local and systemic spread of infection can occur that may result in cellulitis, lymphangitis, or septicaemia. Non-infectious complications of S. pyogenes infection include guttate psoriasis, scarlet fever, and glomerulonephritis (an inflammation of the kidney that can lead to kidney failure). It is thought that most cases of glomerulonephritis result from streptococcal impetigo rather than streptococcal throat infection, and this has always been an important rationale for antibiotic treatment. The incidence of acute glomerulonephritis has declined rapidly over the last few decades. Baltimore 1985 stated that the risk of developing glomerulonephritis is not altered by treatment of impetigo; however, certain subtypes of Group A streptococci are associated with a much greater risk (Dillon 1979b).
In the Netherlands, most people with impetigo consult their general practitioner and only approximately 1% of the cases are referred to a dermatologist (Bruijnzeels 1993). Although the incidence of impetigo in general practice has been declining, recent data show an increase in consultations for impetigo (Koning 2006; Van den Bosch 2007). Impetigo is still a common disease particularly in young children. It is the third most common skin disorder in children after dermatitis/eczema and viral warts (Bruijnzeels 1993; Dagan 1993; Mohammedamin 2006). Impetigo is the most common skin infection that is presented in general practice by children aged one to four years of age (Mohammedamin 2006). In British general practice, 2.8% of children aged 0 to 4 and 1.6% aged 5 to 15 consult their GP about impetigo each year (McCormick 1995). In the Netherlands in the late 1980s, the consultation rate was 1.7% of all children under 18 years of age; this increased to 2.1% in 2001 (Koning 2006). Peak incidence occurs between the ages of one and eight years (Koning 2006). In some tropical or developing countries the incidence of impetigo seems to be higher than elsewhere (Canizares 1993; Kristensen 1991).
Management options for impetigo include the following:
no pharmacological treatment, waiting for natural resolution, hygiene measures;
topical disinfectants (such as saline, hexachlorophene, povidone iodine, and chlorhexidine);
topical antibiotics (such as neomycin, bacitracin, polymyxin B, gentamycin, fusidic acid, mupirocin, retapamulin, or topical steroid/antibiotic combination); and
systemic antibiotics (such as penicillin, (flu)cloxacillin, amoxicillin/clavulanic acid, erythromycin, and cephalexin).
The aim of treatment includes resolving the soreness caused by lesions and the disease's unsightly appearance (especially on the face), as well as preventing recurrence and spread to other people. An ideal treatment should be effective, cheap, easy to use, and accepted by people. It should be free from side-effects, and it should not contribute to bacterial resistance. For this reason, antibiotics should not have an unnecessarily broad spectrum (Espersen 1998; Smeenk 1999), and if a topical antibiotic is used, it should, preferably, not be one which may be needed for systemic use (Carruthers 1988; Smeenk 1999).
Waiting for natural resolution could be acceptable if the natural history were known and benign. Impetigo is considered to be self-limiting by many authors (Hay 1998; Resnick 2000). However, there are no robust data on the natural history of impetigo. Reported cure rates of placebo creams vary from 8% to 42% at 7 to 10 days (Eells 1986; Ruby 1973). Topical cleansing used to be advised in the 1970s as an alternative for antibiotic treatment, but this was later said to be no more effective than placebo (Dagan 1992). Guidelines and treatment advice often do not mention topical cleansing as a treatment because the main concern is preventing the spread of the infection to other children.
A choice has to be made between topical and systemic antibiotic treatment, although in some situations clinicians prescribe both topical and systemic antibiotics. An advantage of the use of topical antibiotics is that the drug can be applied where it is needed, avoiding systemic side-effects such as gastrointestinal upset. Also, compliance may be better (Britton 1990).
The disadvantages of using topical antibiotics include the risks of developing bacterial resistance and sensitisation, e.g. developing an allergic contact dermatitis to one of the constituents of the topical preparation (Carruthers 1988; Smeenk 1999). This is especially common with the older antibiotics, such as gentamycin, bacitracin, and neomycin (Smeenk 1999). Some preparations (e.g. tetracycline) can cause staining of the skin and clothes.
Staphylococcal resistance against penicillin and erythromycin is common (Dagan 1992). Bacterial resistance against the newer topical antibiotics, such as mupirocin ointment and fusidic acid ointment, is increasing (Alsterholm 2010; de Neeling 1998). Another advantage of the newer topical antibiotics is that mupirocin is never, and fusidic acid not often, used systemically.
All treatment options listed above aim to either eradicate or prevent growth of the bacteria.
Guidelines concerning treatment vary widely - some recommend oral antibiotic treatment, others local antibiotic treatment or even just disinfection in mild cases (Hay 1998; Resnick 2000) - so clinicians have many treatment options. The evidence on what works best is not clear. There is potential conflict between what is in the best interest of the individual and what would best benefit the community in terms of cost and the increase in antibiotic resistance.
To assess the effects of treatments for impetigo, including waiting for natural resolution.
We included randomised controlled trials.
We included people who have impetigo or impetigo contagiosa diagnosed by a medically trained person (and preferably confirmed by bacterial culture). We recorded whether or not bacterial culture was performed. The diagnosis could be either non-bullous or bullous impetigo. Studies using a broader diagnostic category such as 'bacterial skin infections' or 'pyoderma' were eligible if a specific subgroup with impetigo could be identified, for which the results were separately described. Studies on secondary impetigo or impetiginised dermatoses were included.
We included any program of topical or systemic (oral, intramuscular, or intravenous) treatment, including antibiotics, disinfectants, or any other intervention for impetigo, such as 'awaiting natural response'. We excluded studies that only compared different dosages of the same drug.
1) Cure as defined by clearance of crusts, blisters, and redness as assessed by the investigator.
2) Relief of symptoms such as pain, itching, and soreness as assessed by participants.
1) Recurrence rate.
2) Adverse effects such as pain, allergic sensitisation, and complications.
3) Development of bacterial resistance.
We aimed to identify all relevant randomised controlled trials (RCTs) regardless of language or publication status (published, unpublished, in press, or in progress).
We updated our searches of the following databases on 27 July 2010:
the Cochrane Skin Group Specialised Register using the following search terms: (impetig* or pyoderma or ((staphylococc* or streptococc*) and skin and infection*)) and (therap* or treatment* or intervention*);
the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library using the search strategy in Appendix 1;
MEDLINE (from 2005 to the present) using the search strategy in Appendix 2;
EMBASE (from 2007 to the present) using the search strategy in Appendix 3; and
LILACS (Latin American and Caribbean Health Science Information database, from 1982 to the present) using the search strategy in Appendix 4.
Please note: The UK and US Cochrane Centres have an ongoing project to systematically search MEDLINE and EMBASE for reports of trials which are then included in the CENTRAL database. Searching has currently been completed in MEDLINE, from inception to 2004 and in EMBASE, from inception to 2006. Further searches of these two databases to cover the years not searched by the UK and US Cochrane Centres for CENTRAL were undertaken for this review as described above.
A final prepublication search for this review was undertaken on 16 August 2011. Although it has not been possible to incorporate RCTs identified through this search within this review, relevant references are listed under Studies awaiting classification. They will be incorporated into the next update of the review.
We updated our searches of the following ongoing trials databases on 3 August 2010, using the terms 'impetigo' and 'pyoderma':
The metaRegister of Controlled Trials (www.controlled-trials.com).
The US National Institutes of Health Ongoing TrialsRegister (www.clinicaltrials.gov).
The Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).
The World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch).
The Ongoing Skin Trials Register (www.nottingham.ac.uk/ongoingskintrials).
We handsearched the Yearbook of Dermatology (1938 to 1966) and the Yearbook of Drug Therapy (1949 to 1966) for the pre-PubMed era.
We checked references from published studies, including secondary review articles, for further studies.
We corresponded with authors and pharmaceutical companies to search for unpublished studies and grey literature.
We did not apply any language restrictions.
Two authors (JCvdW and SK or RvdS) independently read all abstracts or citations of trials. If one of the authors thought the article might be relevant, a full copy of the article was acquired for further data collection. The reasons for exclusion were recorded for every excluded abstract or citation. Only full reports were included. Two authors independently screened all full-copy articles (LvSS, SK, RvdS, JCvdW). The articles were selected according to the inclusion criteria. Reasons for exclusion were recorded on a specially-designed registration form (see the 'Characteristics of excluded studies' table). In the case of doubt, the opinion of a third author was obtained. Many trials studied a range of (skin) infections including impetigo. Frequently, the results of the subgroup of impetigo participants were not reported separately. In these studies, provided they were published in the last 10 years, we contacted trial authors and asked them to provide the results of the subgroup of impetigo participants. We obtained data in this way in only two instances (Blaszcyk 1998; Claudy 2001).
Two authors (ADM and CCB), using a pre-piloted data abstraction form, carried out the full data extraction. The form contained key elements such as time and setting of the study, participant characteristics, bacterial characteristics, type of interventions, outcomes, and side-effects. We resolved disagreements with the help of a third author (SK).
For this update, RvdS and JCvdW carried out data extraction from newly included papers. When studies assessed outcome measures more than once, we included the assessment that was nearest to one week after the start of therapy. When studies had more than two arms and two of these arms were different dosages of the same drug, we combined these arms.
Two independent authors (JCvdW, RvdS and/or AV) assessed the methodological quality of all trials according to the updated guidelines (Higgins 2008). Because we could not read the Japanese study by Ishii 1977, this 'Risk of bias' table was completed by Tetsuri Matsumura. The two studies on which authors of this review were co-authors (Koning 2003; Koning 2008) were assessed by other authors. The items that were addressed are shown in the 'Risk of bias' table. For feasibility reasons, the methodological quality assessment was not performed under masked conditions. There is no consensus over whether assessment should be done blinded for authors, institutions, journal, or publication year (Jadad 1998).
In the case of studies with more than two treatment arms, we deemed that pooling these studies under separate comparisons, without adjustment, would result in unit-of-analysis errors (overcounting). Should this have occurred, the problem was to be solved by dividing the group size by the number of comparisons.
We used the I² statistic to assess statistical heterogeneity, with I² statistic > 50% regarded as substantial heterogeneity.
Where there was no statistical evidence of heterogeneity we used the fixed-effect model to estimate effects. Otherwise, we used the random-effects model. For dichotomous outcomes we reported risk ratios with 95% confidence intervals.
We prespecified the following factors for sensitivity analyses:
the quality of the studies;
whether there was observer blinding;
whether there was just a clinical diagnosis or bacterial swab confirmation;
primary versus secondary impetigo;
bullous versus non-bullous; and
staphylococcal or streptococcal predominance.
During the update, we decided that an overall quality score per study was not useful. Furthermore, most trials were observer-blind, took bacterial swabs, studied primary impetigo, and had staphylococcal predominance. Sensitivity analyses for these items were, therefore, not possible.
When we analysed the data we decided to consider the results for bullous and non-bullous impetigo separately.
Our initial search identified approximately 700 papers, 221 of which were selected for full copy reading. For this update, we identified more than 1000 additional papers. Two reviewers screened titles and abstracts, after which, approximately, 60 papers were studied in full copy.
For the first version of the review we included 56 papers describing 57 trials. This update identified 12 additional studies, of which 2 were published before 2000 (Farah 1967; Ishii 1977). One study, which was previously included, was excluded because it turned out not to be a randomised trial (Park 1993), bringing the total number of included studies to 68. The lists of ongoing studies (Ongoing studies) and studies awaiting assessment (Studies awaiting classification) show studies that might be eligible for a future update of this review. Regarding the excluded studies, we only report on the most relevant ones (Excluded studies; Characteristics of excluded studies).
Most trials were reported in the English language. Four included studies were reported in Japanese, and one paper each was reported in Thai, Portuguese, Spanish, French, and Danish (some of these had abstracts and tables in English). Trials in Russian, Chinese, German, and French were among those that were excluded (not for language reasons). In instances where none of the authors were competent in the language of the paper, translators provided assistance.
We found an appreciable number of studies from the early 1940s (e.g. MacKenna 1945). These studies were often carried out in military populations, in which impetigo was a frequent disease at the time. These study reports did not meet the inclusion criteria of our review because of inadequate randomisation. The distribution of the included studies by decade is as follows: 1960s - 1 study, 1970s - 5 studies (7%), 1980s - 31 studies (46%), 1990s - 20 studies (29%), and 2000 to 2008 - 11 studies (16%). Five included studies evaluating mupirocin were presented at an international symposium in 1984; we found no publication other than the conference proceedings for three of these (Kennedy 1985; Rojas 1985; Wainscott 1985). Two were published elsewhere as well (Eells 1986; Gould 1984).
All studies were parallel group trials, but there were important design differences between the studies. As mentioned before, many trials included participants with infections other than impetigo, while some trials studied only impetigo. Ages of included participants differed widely, as some studies were carried out exclusively in either adults or children. The average age of study participants in trials that studied a range of skin infections was usually higher than in studies focusing on impetigo alone. With the exception of four studies (Faye 2007; Ishii 1977; Rice 1992; Vainer 1986), all studies performed bacteriological investigations. Although a number of studies explicitly stated that participants with a negative culture were excluded, other studies may also have excluded culture negative participants without reporting those exclusions. No study reported a predominantly streptococcal impetigo. The only studies not to report a preponderance of staphylococcal impetigo were Mertz 1989 and Ruby 1973 (carried out in Puerto Rico and Texas respectively).
The 68 studies had a total of 5578 evaluable participants; this is an average of 82 participants and a median of 60.5 participants per study (see the 'Characteristics of included studies' tables). In 23 studies the number of participants with impetigo was less than 50; in 10 studies it was less than 20.
Twenty-nine of the studies were carried out in North America (in 13 Canadian/Northern states, in 8 Southern states, in 8 multicentres), 15 in Europe, 9 in Central/South America, 10 in Asia, 1 in Africa, and 4 were worldwide multicentre trials. Most studies were carried out in hospital out-patient clinics (paediatrics or dermatology, 60 studies), but some were carried out in general practice.
Only three studies exclusively addressed participants with bullous impetigo (Dillon 1983; Ishii 1977; Moraes Barbosa 1986). Seven trials included both bullous and non-bullous impetigo participants (Barton 1989; Ciftci 2002; Dagan 1992; Koning 2008; Kuniyuki 2005; Oranje 2007; Pruksachat 1993). Three studies on secondary impetigo were included (Fujita 1984; Rist 2002; Wachs 1992). Three other trials included both primary and secondary impetigo participants (Faye 2007; Gonzalez 1989; Tamayo 1991). Thirty-nine trials studied impetigo alone whereas 29 trials studied participants with a range of (usually skin) infections, impetigo being 1 of them. This was the typical study design when a new antibiotic was studied. This type of study design imposed problems in retrieving outcome data as the outcomes were often presented for all the participants together. We included these studies only if the main outcome measure was presented separately for the subgroup of impetigo participants.
The 68 trials evaluated 50 different treatments (26 oral treatments and 24 topical treatments - both including placebo). The systemic treatments that were studied were all administered orally (tablets). A total of 74 different comparisons were made. Some comparisons were made in several studies; some studies made more than one comparison. Sixty-eight comparisons were made only once. Six different comparisons were made in more than 1 trial, especially when topical mupirocin was studied (topical mupirocin versus oral erythromycin was considered in 10 studies, mupirocin versus fusidic acid was considered in 4 studies, mupirocin versus placebo was considered in 3 studies). For each of these comparisons we pooled the outcomes of the different studies (see Data and analyses).
The most common type of comparison was between 2 different oral antibiotic treatments (29 studies including duplicates). Cephalosporins (15 studies) and macrolide antibiotics, especially erythromycin and azithromycin (9 studies), were most often involved. A topical antibiotic treatment was compared with an oral antibiotic treatment in 22 studies. Nineteen of these comparisons contained erythromycin, mupirocin, or both.
Only two trials studied antiseptic or disinfecting treatments (Christensen 1994; Ruby 1973).
Only seven placebo controlled trials were found (Eells 1986; Gould 1984; Ishii 1977; Koning 2003; Koning 2008; Rojas 1985; Ruby 1973). The latter is the only trial that compared an oral treatment with placebo.
Three studies had three arms but the treatment in two of these were different dosages of the same drug (Blaszcyk 1998; Bucko 2002a; Bucko 2002b). We combined these arms. Nine other studies had more than two arms but with different treatments: three arms (Bass 1997; Demidovich 1990; Dux 1986; Rodriguez-Solares 1993; Vainer 1986; Wachs 1976), four arms (Kuniyuki 2005; Moraes Barbosa 1986), and five arms (Ruby 1973). Only two of the comparisons in these multiple-arm studies could be pooled with other studies: erythromycin versus penicillin V from Demidovich 1990, and mupirocin versus erythromycin from Dux 1986. For this reason we refrained from adjusting for multiple treatment comparisons.
Cure as assessed by investigator was our main outcome measure. This was often not defined. Researchers sometimes combined the categories 'cured' and 'improved' and presented those participants as one group. The length of follow-up varied widely, and it was sometimes not even specified; however, we tried to retrieve the data for follow up as close as possible to seven days after the start of treatment. The development of bacterial resistance to the study drug was reported in only 10 studies.
One hundred and sixty-five of the studies did not meet the inclusion criteria for the first version of the review, and 33 more were excluded when updating the review (see the 'Characteristics of excluded studies' tables). The most common reasons included the following: the study was not about impetigo, the outcomes of impetigo participants were not reported separately, or studies were not randomised.
In the previous version of this review, four studies were awaiting classification. For this update two of these studies were included (Ciftci 2002; Claudy 2001) and two were excluded (Liu 1986; Parish 2000).
Ten studies that were found during the update process are listed in the 'Characteristics of studies awaiting classification' tables, as are a further 6 studies that were identified at the prepublication search. We are currently unable to include or exclude these due to insufficient information about them. We hope to fully incorporate them into future updates of this review.
Seven studies that were found during the update process are listed in the 'Characteristics of ongoing studies' tables. These will be fully incorporated into future updates of this review when they are completed.
For many of the items that were assessed, the studies did not provide enough information (Figure 1; Figure 2).
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Fourteen of the studies reported an adequate generation of the randomisation scheme. All other papers did not report on this item.
All but two of the included studies were described as randomised as this was a selection criterion. For two papers in Japanese, this was unclear, and these papers were given the benefit of the doubt (see Figure 1). Most papers did not describe the method of randomisation in detail, so the method could not be judged as appropriate. Only 19 of the 68 studies provided information on allocation concealment. In most cases (18 of 19), treatment allocation was considered to be concealed.
In many cases it was not clear whether the participant, the caregiver, or the outcome assessor were blinded. A total of 15 studies were considered to be adequately blinded (see Figure 1). In 24 studies, at least 1 party was considered not to be blinded. In 29 papers, the information was insufficient to judge blinding.
In 10 of our included studies, the inclusion and exclusion criteria of the trial were not specified in more detail than saying 'patients with impetigo' (see Figure 1).
In some studies, high numbers lost to follow up were recorded. Thirty-four studies either included an intention-to-treat analysis or had fewer than 10% dropouts balanced between groups. For some other studies, an intention-to-treat analysis could be calculated from the data presented in the study.
The first primary outcome was clinical cure (or improvement) as assessed by the investigator. When this was assessed more than once, we only included the assessment that was nearest one week from commencement of treatment.
Under the following two main headings ('non-bullous impetigo' and 'bullous impetigo') we have grouped all studies that either included only primary impetigo, combined primary and secondary impetigo, or did not specify whether participants had primary or secondary impetigo. The third heading 'secondary impetigo' addresses all studies that focused exclusively on secondary impetigo (see Background for an explanation).
Overall topical antibiotics showed better cure rates or more improvement than placebo (pooled risk ratio (RR) 2.24, 95% CI 1.16 to 3.13 using a random-effects model, I² = 53%) (see Analysis 1.1). This result was consistent for mupirocin (RR 2.21, 95% CI 1.59 to 3.05; 3 studies - Eells 1986; Gould 1984; Rojas 1985) (see Analysis 1.1), fusidic acid (RR 4.42, 95% CI 2.39 to 8.17; 1 study - Koning 2003) (see Analysis 1.1), and retapamulin (RR 1.64, 95% CI 1.30 to 2.07; 1 study - Koning 2008) (see Analysis 1.1). In one small study (Ruby 1973), bacitracin did not show a significant difference in cure rate compared with placebo (RR 3.71, 95% CI 0.16 to 85.29) (see Analysis 1.1).
Only one topical antibiotic showed superiority over another topical antibiotic - in a single study: gentamycin over neomycin (RR 1.43, 95% CI 1.03 to 1.98; Farah 1967) (see Analysis 2.1). Also from a single study, the difference between retapamulin over fusidic acid was not statistically significant (RR 1.05, 95% CI 1.00 to 1.11; Oranje 2007) (see Analysis 2.1). There were 12 different comparisons: 4 studies (Gilbert 1989; Morley 1988; Sutton 1992; White 1989) compared mupirocin with fusidic acid (RR 1.03, 95% CI 0.95 to 1.11) (see Analysis 2.1), and the remaining 11 were all only represented by a single study.
Pooling 10 studies which compared mupirocin with oral erythromycin showed significantly better cure rates, or more improvement, with mupirocin (RR 1.07, 95% CI 1.01 to 1.13) (see Analysis 3.1). However, no significant differences were seen between mupirocin and dicloxacillin (Arredondo 1987), cephalexin (Bass 1997), or ampicillin (Welsh 1987). Bacitracin was significantly worse than oral cephalexin in one small study (Bass 1997), but no difference was seen between bacitracin and erythromycin (Koranyi 1976), or penicillin (Ruby 1973).
A sensitivity analysis on the influence of blinding the outcome assessor on the comparison of mupirocin versus erythromycin (10 studies) revealed that there was no clear relationship between blinding of the outcome assessor and the outcome.
Pooling the 2 studies with observer blinding (Britton 1990; Dagan 1992) showed high heterogeneity (I² statistic = 79%) and resulted in a non-significant difference between the 2 drugs (random-effects model, RR 1.12, 95% CI 0.86 to 1.46) (see Analysis 3.2).
In one study (Ruby 1973), no statistically significant difference in cure/improvement was seen when bacitracin was compared to hexachlorophene (RR 3.71, 95% CI 0.16 to 85.29) (see Analysis 4.1). In another study (Christensen 1994), there was a tendency for fusidic acid cream to be more effective than hydrogen peroxide, but this just failed to reach statistical significance (RR 1.14, 95% CI 1.00 to 1.31) (see Analysis 4.1). When the 2 studies were pooled, topical antibiotics were significantly better than disinfecting treatments (fixed-effect model, RR 1.15, 95% 1.01 to 1.32, I² statistic 0%) (see Analysis 4.1).
Only one study compared a topical antibiotic to an antifungal, comparing topical mupirocin to topical terbinafine (Ciftci 2002). No statistical difference was seen (RR 1.39, 95% CI 0.98 to 1.96) (see Analysis 5.1).
In a four-armed study, three arms addressed the following combinations of a topical antibiotic and an oral antibiotic: topical tetracycline combined with oral cefdinir compared to topical tetracycline combined with oral minomycin, topical tetracycline combined with oral cefdinir compared to topical tetracycline combined with oral fosfomycin, and topical tetracycline combined with oral minomycin compared to topical tetracycline combined with oral fosfomycin (Kuniyuki 2005). None of the three comparisons showed a statistically significant difference (see Analysis 6.1).
The fourth arm of the study described under the previous heading (Kuniyuki 2005) was tetracycline. None of the comparisons with the other three treatments (see above) showed a statistically significant difference (see Analysis 7.1).
A single study (Ruby 1973) found no significant difference between oral penicillin and placebo (RR 7.74, 95% CI 0.43 to 140.26) (see Analysis 8.1).
All comparisons consisted of single studies (or arms of a single study); only one comparison - cephalexin versus penicillin - showed a significant difference (Demidovich 1990) (see Analysis 9.1).
No significant differences were seen between cephalexin and cefadroxil (Hains 1989), cefdinir (Giordano 2006; Tack 1997; Tack 1998); cefaclor and cefdinir (Arata 1989a), or cefditoren and cefadroxil (Bucko 2002b). Cefditoren turned out to be less effective than cefuroxime (Bucko 2002a) (see Analysis 10.1).
In two studies (Barton 1987; Demidovich 1990), erythromycin showed a better cure rate or more improvement than penicillin (pooled fixed-effect model, RR 1.29, 95% CI 1.07 to 1.56, I² statistic 0%) (see Analysis 11.1). The other five comparisons consisted of single studies, and they did not show significant differences between macrolides and penicillins.
In a single study (Daniel 1991a), no difference in cure rate or improvement was seen between azithromycin and erythromycin (RR 1.18, 95% CI 0.88 to 1.58) (see Analysis 12.1).
In 1 study (Dagan 1989), amoxicillin plus clavulanic acid showed a better cure rate than amoxicillin alone (RR 1.40, 95% CI 1.04 to 1.89) (see Analysis 13.1), but when amoxicillin plus clavulanic acid was compared with fleroxacin in another study (Tassler 1993), no significant difference was seen (RR 1.14, 95% CI 0.80 to 1.62) (see Analysis 13.1). Cloxacillin was significantly superior to penicillin in 2 studies (Gonzalez 1989; Pruksachat 1993) although these studies were statistically heterogeneous (I² statistic 57%) (pooled RR 1.59, 95% CI 1.21 to 2.08) (see Analysis 13.1).
In two studies (Arata 1989b; Claudy 2001), no difference in cure rates/improvement could be detected between lomefloxacin and norfloxacin nor between (oral) fusidic acid and pristinamycin (see Analysis 14.1).
In a single small study (Ruby 1973), no difference in cure rates/improvement could be detected between penicillin and hexachlorophene (RR 7.74, 95% CI 0.43 to 140.26) (see Analysis 15.1).
In a single small study (Ruby 1973), no participants in either the hexachlorophene (n = 11) or placebo group (n = 13) showed cure or improvement. Comparisons of disinfecting treatments with antibiotics are given above.
In one study (Ishii 1977), topical Eksalbe simplex (a drug containing killed Eschelichia, Staphylococcus, Streptococcus, and Pseudomonas) was compared to placebo. The active drug turned out to be superior (cure/improvement RR 2.30, 95% CI 1.10 to 4.79) (see Analysis 16.1).
In a small study (Moraes Barbosa 1986), fusidic acid was significantly more effective than both neomycin/bacitracin (RR 10.00, 95% CI 1.51 to 66.43) (see Analysis 17.1) and chloramphenicol (RR 5.00, 95% CI 1.38 to 18.17) (see Analysis 17.1). In the same study, no difference was detected between chloramphenicol and neomycin/bacitracin (RR 2.00, 95% CI 0.21 to 19.23) (see Analysis 17.1).
The same study (Moraes Barbosa 1986) showed that neomycin/bacitracin was significantly less effective than oral erythromycin (RR 0.14 95% CI 0.02 to 0.99) (see Analysis 18.1). There was no significant difference between either erythromycin and fusidic acid (RR 1.43, 95% CI 0.83 to 2.45) (see Analysis 18.1) or chloramphenicol (RR 0.29, 95% CI 0.07 to 1.10) (see Analysis 18.1).
No significant difference was seen between cephalexin and dicloxacillin (Dillon 1983; RR 1.17, 95% CI 0.95 to 1.45) (see Analysis 19.1).
No significant difference was seen between mupirocin and cephalexin (Rist 2002) (see Analysis 20.1).
In a three-armed study (Wachs 1976), the comparisons of betamethasone with gentamycin alone or with betamethasone plus gentamycin did not show significant differences (see Analysis 21.1 and Analysis 22.1). The combination of betamethasone and gentamycin cream was significantly more effective than gentamycin alone (RR 2.43, 95% CI 1.29 to 4.57) (see Analysis 23.1).
In a very small study, no significant difference was detected between cephalexin and enoxacin (Fujita 1984) (see Analysis 24.1).
The second primary outcome was relief of symptoms, such as pain, itching, and soreness, as assessed by study participants. Although some studies asked about overall satisfaction, acceptability, or treatment preference (McLinn 1988; Rice 1992; Rist 2002; Sutton 1992; White 1989), only one study asked participants to rate their symptoms at follow-up (Giordano 2006). However, this was a study addressing not only impetigo but other skin infections as well, and results for this outcome were not reported for impetigo separately.
No relevant data were provided by any study for this outcome.
The trials included in this review usually reported few, if any, side-effects from topical antibiotics (see Table 1). The studies comparing mupirocin, bacitracin, and placebo reported none (Eells 1986; Ruby 1973). The study that compared fusidic acid to placebo recorded more side-effects in the placebo group (Koning 2003). Three of 4 studies comparing mupirocin with fusidic acid recorded side-effects: minor skin side-effects were reported for mupirocin by 10 out of 368 participants (3%) and for fusidic acid by 4 out of 242 participants (2%). The study that compared retapamulin to placebo found more itching in the group treated with retapamulin (7% vs 1%; P = 0.17) (Koning 2008). In the other study of retapamulin, this side-effect was reported in less than 1% of cases (Oranje 2007). Most other trials comparing topical antibiotics reported no side-effects or reported minor skin side-effects in low numbers (less than 5% of participants).
| Study | Adverse events: nature and number or percentage by treatment group |
| Arata 1989a; Arata 1989b | mainly gastrointestinal: cefdinir 9/142, cefaclor 4/145 |
| Arredondo 1987 | mupirocin: nil reported dicloxacillin: abdominal pain 1/ 31, vomiting 2/31 |
| Barton 1987 | not reported |
| Barton 1988 | abdominal pain: erythromycin 1/ 49, dicloxacillin 1/51 vomiting + rash: dicloxacillin 1/51 |
| Barton 1989 | gastrointestinal: erythromycin 8/48, mupirocin 4/49 |
| Bass 1997 | not reported |
| Beitner 1996 | diarrhoea: cefadroxil 14/327, flucloxacillin 87/324 (all participants) severe (stomach ache/rash/fever/vomiting): cefadroxil 14/327, flucloxacillin 2/234 (all participants) |
| Blaszcyk 1998 | mainly gastro-intestinal (half of which were considered treatment-related): clindamycin 150 mg (19%), clindamycin 300 mg (17%), dicloxacillin 10% (all participants) |
| Britton 1990 | minor gastrointestinal: 11 total, equally divided |
| Bucko 2002a; Bucko 2002b | unclear and not specified for impetigo participants |
| Christensen 1994 | led to withdrawal: skin irritation 1, burning 1, blistering 1 (all fusidic acid - hydrogen peroxide: 0) mild SE: fusidic acid 9, hydrogen peroxide 13 |
| Ciftci 2002 | burning, stinging, itching: 1 in each group rash: 1 in terbinafine group |
| Claudy 2001 | upper gastrointestinal: fusidic acid 6.8% vs pristinamycin 11.6% lower gastrointestinal: 2.5% vs 16.7% hypersensibility: 1.9% vs 5.8% |
| Dagan 1989 | vomiting: amoxicillin 1, amoxicillin and clavulanic acid (augmentin) 0 diarrhoea: amoxicillin 1, amoxicillin and clavulanic acid (augmentin) 0 |
| Dagan 1992 | gastrointestinal: erythromycin 11/47, mupirocin 4/51 |
| Daniel 1991a; Daniel 1991b | no subgroup data |
| Demidovich 1990 | nil reported |
| Dillon 1983 | not reported |
| Dux 1986 | pruritus: mupirocin 1/78 nausea and abdominal pain: erythromycin 1/50, cloxacillin 0/20 (all participants) |
| Eells 1986 | not reported |
| Esterly 1991 | mupirocin: nil reported erythromycin: stomach pain and nausea 1/20, vomiting and irritability 1/20, hysterical attacks 1/20 |
| Farah 1967 | not reported |
| Faye 2007 | diarrhoea: amoxicillin 2/64 vs erythromycin 11/65 |
| Fujita 1984 | mainly gastrointestinal: enoxacin 11/113, cephalexin 4/110 (all participants) |
| Gilbert 1989 | nil reported |
| Ginsburg 1978 | 1 child removed from cefadroxil group because of vomiting; no other SE reported |
| Giordano 2006 | diarrhoea: cefdinir 10% vs cephalexin 4% nausea: cefdinir 3% vs cephalexin 6% vaginal mycose of females: cefdinir 3% vs cephalexin 6% |
| Goldfarb 1988 | mild diarrhoea: amupirocin 0/30, erythromycin 5/30 |
| Gonzalez 1989 | not reported |
| Gould 1984 | not reported |
| Gratton 1987 | mostly gastrointestinal: erythromycin 8/29 mupirocin: nil reported |
| Hains 1989 | nil reported |
| Ishii 1977 | nil reported |
| Jaffe 1985 | mild diarrhoea: Augmentin® 2/18, cefaclor 5/16 (all participants) |
| Jaffe 1986 | mild staining: hydrocortisone + potassium hydroxyquinoline sulphate cream 2/24, 1% hydrocortisone + 2% miconazole nitrate cream 0/24 |
| Kennedy 1985 | nil reported |
| Kiani 1991 | mainly gastrointestinal: azithromycin 30/182, cephalexin: 20/184 Withdrawn: azithromycin 5 (4 gastrointestinal; 1 dizziness and somnolence), cephalexin 1(euphoria) (all participants) |
| Koning 2003 | mainly pain and burning due to povidone iodine: fusidic acid 7/76, placebo 19/80 |
| Koning 2008 | any: retapamulin 15/139 vs placebo 2/71 application site pruritis: 9 vs 1 |
| Koranyi 1976 | mild abdominal cramps: erythromycin 2/15, bacitracin 0/15 |
| Kuniyuki 2005 | not reported |
| McLinn 1988 | gastrointestinal: mupirocin 0/30, erythromycin 6/30 |
| Mertz 1989 | nil reported |
| Montero 1996 | mild skin side-effects: azythromycin 3/100, cefaclor 2/100 |
| Moraes Barbosa 1986 | not reported |
| Morley 1988 | all local skin reactions: sodium fusidate 2/191, mupirocin 12/163 (all participants) |
| Nolting 1988 | mild burning: sulconazole 0/32, miconazole 1/34 |
| Oranje 2007 | local irritation: retapamulin 6/346 vs sodium fusidate 0/173 |
| Pruksachat 1993 | not reported |
| Rice 1992 | stomach ache/diarrhoea/vomiting/itching/burning (%): erythromycin 24/10/7/5/0, mupirocin 2/2/0/12/10 |
| Rist 2002 | diarrhoea: mupirocin 2/82 vs cephalexin 3/77 |
| Rodriguez-Solares 1993 | gastrointestinal: azithromycin 2/25, dicloxacillin/flucloxacillin 2/14 |
| Rojas 1985 | nausea/vomiting: mupirocin 0/52, vehicle 1/52 |
| Ruby 1973 | not reported |
| Sutton 1992 | local: fusidic acid 2/104, mupirocin 4/97 |
| Tack 1997 | mainly gastrointestinal: cefdinir 16%, cephalexin 11% (all participants) |
| Tack 1998 | no subgroup data was available; it included only participants that had pathogens susceptible to both study drugs |
| Tamayo 1991 | nil reported |
| Tassler 1993 | mainly gastrointestinal: fleroxacin 17%, amoxicillin/clavunalate 21% (all participants) |
| Vainer 1986 | total 3% skin rash: fusidic acid 1/43 burning and itching: tetracycline/polymyxin B ointment and neomycin/bacitracin ointment both 1/44 and 1/41 respectively |
| Wachs 1976 | not reported |
| Wainscott 1985 | nil reported |
| Welsh 1987 | nil reported |
| White 1989 | minor itching or burning: mupirocin 6/263, fusidic acid 2/127 (all participants) |
| Wilkinson 1988 | rash: mupirocin 0/24, neomycin 1/26 (all participants) |
Of the 10 trials comparing erythromycin with mupirocin, 9 reported side-effects. All trials recorded more side-effects from erythromycin, with the exception of two trials (Britton 1990 - equally divided minor gastrointestinal side-effects - and Rice 1992 - nil reported). Gastrointestinal side-effects (nausea, stomach ache, vomiting, diarrhoea) were recorded in 80 out of 297 participants (27%) in the erythromycin groups, versus 17 out of 323 participants (5%) in the mupirocin groups. Skin side-effects (itching, burning) were recorded in 5 out of 297 participants (2%) in the erythromycin groups versus 23 out of 323 participants (7%) in the mupirocin groups. Most other trials comparing topical and oral antibiotics did not record data on side-effects (see Table 1).
Eleven of the 31 trials comparing oral antibiotics did not report on side-effects (see Table 1). Three of the 6 trials that studied erythromycin recorded side-effects; the highest frequency was reported by Faye 2007: 11/65 participants reported gastrointestinal side-effects (mainly diarrhoea). The other trials, usually making unique comparisons, mainly reported gastrointestinal side-effects in small percentages. In five trials, a considerable difference in side-effects was reported. Gastrointestinal complaints were recorded in 1 out of 113 participants (10%) in the enoxacin group compared to 4 out of 110 participants (4%) in the cefalexin group (Fujita 1984). Fourteen out of 327 (4%) of the cefadroxil-treated participants versus 2 out of 234 (1%) flucloxacillin-treated participants had 'severe' side-effects, such as stomach ache, rash, fever, and vomiting (Beitner 1996). Cefaclor caused more diarrhoea than amoxicillin plus clavulanic acid (5 out of 16 participants (31%) vs 2 out of 18 participants (11%)) (Jaffe 1985). Pristinamycin caused more upper and lower gastrointestinal side-effects than oral fusidic acid (12% vs 7% and 17% vs 2%, respectively) (Claudy 2001). Finally, the clindamycin group of participants reported more side-effects (any side-effect) than the dicloxacillin-treated group (Blaszcyk 1998).
Eleven per cent of the participants using hydrogen peroxide cream reported mild side-effects (not specified) versus seven per cent in the fusidic acid group (Christensen 1994). No participant was withdrawn from the study because of side-effects. No adverse effects of scrubbing with hexachlorophene were recorded (Ruby 1973) (see Table 1).
Most studies either did not report on susceptibility of isolated pathogens to the study drugs or presented only baseline data. Ten studies provided information on the development of resistance to the study drug during the study period (Barton 1988; Bucko 2002a; Bucko 2002b; Dagan 1992; Giordano 2006; Goldfarb 1988; Gould 1984; Tack 1998; Tassler 1993; White 1989). In most of these studies, none or only a few of the participants' pathogens had developed resistance. The only exception was Dagan 1992, where 14/18 (78%) of positive cultures after 3 days of follow-up showed resistance to erythromycin, compared to 27/91 (28%) at baseline. The other study that included erythromycin (Goldfarb 1988) showed only 3% (1/32) resistance at follow-up.
Overall, topical antibiotics showed better cure rates than topical placebo. No differences were found between the two most studied topical antibiotics: mupirocin and fusidic acid. Topical mupirocin was superior to oral erythromycin. In most other comparisons, topical and oral antibiotics did not show significantly different cure rates, nor did most trials comparing oral antibiotics. Penicillin V was inferior to erythromycin and cloxacillin, and there is a lack of evidence to suggest that using disinfectant solutions improves impetigo.
The reported number of side-effects was low. Oral antibiotic treatment caused more side-effects, especially gastrointestinal ones, than topical treatment. A striking finding is that the trials comparing erythromycin with mupirocin recorded more (gastrointestinal) side-effects in the erythromycin group than the trials that compared erythromycin with other oral antibiotics.
The large number of treatments evaluated (50) supports the view that there is no widely accepted standard therapy for impetigo. Most studies did not contribute clear answers about the vast choice of treatment options. Many of the studies were underpowered; this is partly due to the fact that many trials included several skin infections, impetigo being only one of them (these studies are directed at the drug rather than at the disease). In many cases, significant differences became insignificant when impetigo participants were considered after excluding participants with other sorts of infection. Another drawback of this type of study is that the age of participants is much higher than the typical age at which people contract impetigo (e.g. Blaszcyk 1998; Bucko 2002a; Bucko 2002b; Kiani 1991). The dosage of studied antibiotics may differ between studies, complicating the comparability of studies; however, the same doses were usually used (e.g. erythromycin 40 mg/kg/day). Cure rates of specific treatments can be different between studies, e.g. of fusidic acid and mupirocin (Sutton 1992; White 1989). This may be explained by the fact that investigations were done in different regions and times, and inclusion criteria differed.
Little is known about the 'natural history' of impetigo. Therefore, the paucity of placebo-controlled trials is striking, given that impetigo can be considered a minor disease. Only seven placebo-controlled studies have been conducted (Eells 1986; Gould 1984; Ishii 1977; Koning 2003; Koning 2008; Rojas 1985; Ruby 1973). The 7-day cure rates of placebo groups in these studies varied but can be considerable (0% to 42%).
The disinfectant agents, such as povidone iodine and chlorhexidine, recommended in some guidelines (Hay 1998; Resnick 2000), usually as supplementary treatment, have been inadequately studied and not compared to placebo treatment. Hydrogen peroxide cream was not significantly less effective than fusidic acid (cure rate 72% versus 82%) in a relatively large trial (Christensen 1994). We judged that blinding in this trial was inadequate.
There is a commonly accepted idea that more serious forms of impetigo (e.g. participants with extensive lesions, general illness, fever) need oral rather than topical antibiotic treatment. This principle cannot be evaluated using the data included in our review as trials that study local treatments usually exclude participants with more serious forms of impetigo.
One of our primary outcomes was relief of symptoms, such as pain, itching, and soreness, as assessed by participants (or parents). Surprisingly, only one of the studies addressed this outcome (Giordano 2006).
Resistance patterns of staphylococci - which causes impetigo - change over time. Outcomes of studies dating back more than 10 years, which form the majority of trials in this review, may not be applicable to the current prevalence of infecting agents. Also, resistance between regions and countries may vary considerably. Thus, up-to-date, local characteristics and resistance patterns of the causative bacteria should always be taken into account when choosing antibiotic treatment. In addition, health authorities and other relevant bodies may advise against prescribing certain antibiotics for impetigo, in order to restrict the development of bacterial resistance and reserve these drugs for more serious infections.
Although the total number of randomised trials we identified was considerable, the average number of participants per study was small. In this update, the newly added studies made this average increase from 62 to 84 per study. This was partly due to studies that assessed a range of infections and randomised a large number of participants, but in which those with impetigo were only a minority. Through the years, we found an increase in the quality of the studies; the average number of items scored positively increased from less than three in the 1970s to almost five for studies published in the new millennium. This is a problem shared with many other reviews. Details of the design of the studies were often lacking in the published reports, leading to a lot of question marks in the 'Risk of bias' tables.
Several studies included participants with impetigo next to participants with other conditions, but they did not report results of those with impetigo separately. However, as the number of participants with impetigo was often small in these studies, we do not expect that our conclusions would be different.
Three authors on this review are authors of one included trial (Sander Koning, Lisette WA van Suijlekom-Smit, Johannes C van der Wouden; Koning 2003), Sander Koning and Johannes C van der Wouden were also involved in a second trial (Koning 2008) which was initiated by the manufacturer of the drug. These authors were not involved in the assessment of the risk of bias for both studies.
Topical mupirocin and fusidic acid can be considered as effective as, or more effective than, oral antibiotics, and these topical agents have fewer side-effects. This finding is in sharp contrast to the previously held view that oral treatment is superior to topical treatment (Baltimore 1985; Tack 1998). Other topical antibiotics, excluding retapamulin, were generally inferior to mupirocin, fusidic acid, and oral antibiotics. The study by Vainer is an exception: no difference was seen between tetracycline/bacitracin cream, neomycin/bacitracin cream, and fusidic acid (Vainer 1986). Fusidic acid, mupirocin, and retapamulin are the only topical antibiotics that have been compared to placebo (and shown to be more effective).
For the results of the study comparing topical fusidic acid to retapamulin (Oranje 2007), the P value computed by Review Manager (RevMan) differs from the study report (0.07 in RevMan vs 0.062 in the study report) due to different methods (94.8% vs 90.1% cure, favouring retapamulin).
None of the studies reported cases of acute (post-streptococcal) glomerulonephritis. This complication has always been an important rationale for oral antibiotic treatment. This reported absence of glomerulonephritis may reflect the reduced importance of streptococci in impetigo. It should be noted that study sizes are small and glomerulonephritis is rare.
Several of the interventions used for impetigo have also been applied in other situations where Staphylococcus aureus, the main bacterium causing impetigo, plays a role. Here we review some of these, as reported in recently published Cochrane reviews. The effect of mupirocin ointment for preventing S. aureus infections in nasal carriers was superior to that of placebo or no treatment (van Rijen 2008). Birnie 2008 assessed interventions to reduce S. aureus in the management of atopic eczema, but the review did not find clear evidence of benefit for any of these. A review of the treatment of bacteraemia due to S. aureus is under way (Cheng 2009), as is a review of antibiotics for S. aureus pneumonia in adults (Shankar 2007). Mastitis in breastfeeding women is also caused by S. aureus. A recent Cochrane review found insufficient evidence to confirm or refute the effectiveness of antibiotic therapy (Jahanfar 2009).
There is a lack of evidence from RCTs for the value of disinfecting measures in the treatment of impetigo, as a sole or supplementary treatment.
There is good evidence that the topical antibiotics mupirocin and fusidic acid are equal to, or possibly more effective than, oral treatment for people with limited disease. Fusidic acid, mupirocin, and retapamulin are probably equally effective; other topical antibiotics seem less effective. In general, oral antibiotics have more side-effects than topical antibiotics, especially gastrointestinal side-effects.
What is stated in the previous paragraph regarding the comparison with topical antibiotics is equally relevant here. The only oral antibiotic that has been compared to placebo is penicillin, and this was in an old study (Ruby 1973): no difference was found, and the confidence interval was large. Based on the available evidence on efficacy, no clear preference can be given for B-lactamase resistant narrow-spectrum penicillins such as cloxacillin, dicloxacillin and flucloxacillin, or for broad spectrum penicillins such as ampicillin, amoxicillin with clavulanic acid, cephalosporins or macrolides.
Other criteria, such as price, (unnecessary) broadness of spectrum, and wish to reserve a particular antibiotic for specific conditions, can be decisive. Resistance rates against erythromycin seem to be rising. In general, oral antibiotics have more side-effects, especially gastrointestinal ones. There is insufficient evidence to say whether oral antibiotics are better than topicals for more serious and extensive forms of impetigo. From a practical standpoint, oral antibiotics might be an easier option for people with very extensive impetigo.
Trials should be powered to compare treatments for a specific disease entity, rather than the effectiveness of a specific antibiotic on a variety of (skin) infections, as treatment may impact differently on separate subtypes of skin and soft tissue infections. As seen in this review, trials that study one treatment for several diseases often show inconclusive results for specific diagnoses. Future research on impetigo should make a careful power calculation as most included studies included too few participants with impetigo to meaningfully assess differences in treatment effect.
Establishing the natural course of impetigo without any form of antibiotic treatment would be useful. However, although impetigo can be considered a minor ailment, studies with a non-intervention arm seem ethically impracticable. Comparator treatments may include the best identified options for non-antibiotic management.
The relative absence of data on the efficacy of topical disinfectants is a research gap that needs to be filled. These agents may not contribute to antibiotic resistance, and they are cheap. This research may be of particular importance for developing countries.
Preferably, a trial on impetigo should:
not include participants with a variety of skin diseases and soft tissue infections. If it does, results should be presented separately by diagnosis;
focus on either bullous or non-bullous impetigo and on either primary or secondary impetigo;
report resistance rates of causative bacteria against the studied antibiotic and against reference antibiotics such as erythromycin, mupirocin and/or fusidic acid, at baseline and at follow-up;
use clear and objective outcome measures for cure and improvement of impetigo, instead of subjective judgements such as 'improved', 'satisfactory', and 'good response'. Key elements defining clinical cure could be absence of crusts, dryness, intactness, and absence of redness of skin. A parameter of improvement could be 'size of affected surface'. Choosing 'standard' follow-up periods, e.g. 7, 14, or 21 days, will facilitate the comparison of studies; and
include a placebo group, or at least a 'gold standard' reference group. For topical treatments, mupirocin or fusidic acid could be considered 'gold standard'.
As part of the issue of antibiotic resistance, impetigo studies that establish the contribution of the studied treatment to the development of bacterial resistance are desirable.
The authors would like to thank the following people from the editorial base for their substantial contribution to this review: Finola Delamere, Philippa Middleton, and Tina Leonard. They would also like to thank Seungsoo Sheen for his help in assessing a Korean paper, Mingming Zhang for assessing two Chinese papers, Alain Claudy for providing the outcomes for the participants with impetigo in his study, and Tetsuri Matsumura for assessing the risk of bias and extracting data from Ishii 1977.
The Cochrane Skin Group editorial base would like to thank the following people who commented on this update: our Key Editor Sue Jessop, our Statistical Editor Jo Leonardi-Bee, our Methodological Editor Philippa Middleton, Inge Axelson who was the clinical referee, and Philip Pocklington who was the consumer referee.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 6 | 575 | Risk Ratio (M-H, Random, 95% CI) | 2.24 [1.61, 3.13] |
| 1.1 Mupirocin | 3 | 173 | Risk Ratio (M-H, Random, 95% CI) | 2.18 [1.58, 3.00] |
| 1.2 Fusidic acid | 1 | 156 | Risk Ratio (M-H, Random, 95% CI) | 4.42 [2.39, 8.17] |
| 1.3 Bacitracin | 1 | 36 | Risk Ratio (M-H, Random, 95% CI) | 3.71 [0.16, 85.29] |
| 1.4 Retapamulin | 1 | 210 | Risk Ratio (M-H, Random, 95% CI) | 1.64 [1.30, 2.07] |
Comparison 1 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs placebo (P), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 14 | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Mupirocin vs rifamycin | 1 | 17 | Risk Ratio (M-H, Fixed, 95% CI) | 1.72 [0.96, 3.07] |
| 1.2 Mupirocin vs neomycin | 1 | 32 | Risk Ratio (M-H, Fixed, 95% CI) | 1.29 [0.98, 1.71] |
| 1.3 Mupirocin vs bacitracin | 1 | 16 | Risk Ratio (M-H, Fixed, 95% CI) | 2.57 [0.97, 6.80] |
| 1.4 Mupirocin vs chlortetracycline | 1 | 14 | Risk Ratio (M-H, Fixed, 95% CI) | 1.11 [0.78, 1.59] |
| 1.5 Mupirocin vs polymyxin B/neomycin | 1 | 8 | Risk Ratio (M-H, Fixed, 95% CI) | 1.06 [0.56, 2.01] |
| 1.6 Fusidic acid vs neomycin/bacitracin | 1 | 84 | Risk Ratio (M-H, Fixed, 95% CI) | 0.92 [0.66, 1.27] |
| 1.7 Fusidic acid vs tetracycline/polymyxin B | 1 | 87 | Risk Ratio (M-H, Fixed, 95% CI) | 1.06 [0.75, 1.52] |
| 1.8 Retapamulin vs fusidic acid | 1 | 517 | Risk Ratio (M-H, Fixed, 95% CI) | 1.05 [1.00, 1.11] |
| 1.9 Sulcanozol vs miconazole | 1 | 66 | Risk Ratio (M-H, Fixed, 95% CI) | 5.31 [0.66, 43.04] |
| 1.10 Hydrocortisone + hydroxyquinoline vs hydrocortisone + miconazole | 1 | 43 | Risk Ratio (M-H, Fixed, 95% CI) | 2.06 [0.89, 4.76] |
| 1.11 Gentamycin vs neomycin | 1 | 128 | Risk Ratio (M-H, Fixed, 95% CI) | 1.43 [1.03, 1.98] |
| 1.12 Mupirocin vs fusidic acid | 4 | 440 | Risk Ratio (M-H, Fixed, 95% CI) | 1.03 [0.95, 1.11] |
Comparison 2 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs another topical (Top) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 15 | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Mupirocin vs erythromycin | 10 | 581 | Risk Ratio (M-H, Fixed, 95% CI) | 1.07 [1.01, 1.13] |
| 1.2 Mupirocin vs dicloxacillin | 1 | 53 | Risk Ratio (M-H, Fixed, 95% CI) | 1.04 [0.94, 1.15] |
| 1.3 Mupirocin vs cephalexin | 1 | 17 | Risk Ratio (M-H, Fixed, 95% CI) | 0.95 [0.66, 1.37] |
| 1.4 Mupirocin vs ampicillin | 1 | 13 | Risk Ratio (M-H, Fixed, 95% CI) | 1.78 [0.65, 4.87] |
| 1.5 Bacitracin vs erythromycin | 1 | 30 | Risk Ratio (M-H, Fixed, 95% CI) | 0.5 [0.22, 1.11] |
| 1.6 Bacitracin vs penicillin | 1 | 34 | Risk Ratio (M-H, Fixed, 95% CI) | 0.38 [0.04, 3.25] |
| 1.7 Bacitracin vs cephalexin | 1 | 19 | Risk Ratio (M-H, Fixed, 95% CI) | 0.37 [0.14, 0.95] |
| 2 Cure/improvement | 2 | 137 | Risk Ratio (M-H, Random, 95% CI) | 1.12 [0.86, 1.46] |
| 2.1 Mupirocin vs erythromycin: observer blinded studies | 2 | 137 | Risk Ratio (M-H, Random, 95% CI) | 1.12 [0.86, 1.46] |
Comparison 3 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
Comparison 3 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab), Outcome 2 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 2 | 292 | Risk Ratio (M-H, Fixed, 95% CI) | 1.15 [1.01, 1.32] |
| 1.1 Bacitracin vs hexachlorophene | 1 | 36 | Risk Ratio (M-H, Fixed, 95% CI) | 3.71 [0.16, 85.29] |
| 1.2 Fusidic acid vs hydrogen peroxide | 1 | 256 | Risk Ratio (M-H, Fixed, 95% CI) | 1.14 [1.00, 1.31] |
Comparison 4 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs disinfecting treatments (Dt), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Mupirocin vs terbinafine | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 5 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs antifungal (Af), Outcome 1 Cure.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Tetracyclin + cefdinir vs tetracyclin + minomycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.2 Tetracyclin + cefdinir vs tetracyclin + fosfomycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.3 Tetracyclin + minomycin vs tetracyclin + fosfomycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 6 Non-bullous impetigo: topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab) vs topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab), Outcome 1 Cure.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Tetracyclin vs tetracyclin + cefdinir | 1 | 34 | Risk Ratio (M-H, Fixed, 95% CI) | 1.57 [0.69, 3.58] |
| 1.2 Tetracyclin vs tetracyclin + minomycin | 1 | 33 | Risk Ratio (M-H, Fixed, 95% CI) | 0.85 [0.62, 1.15] |
| 1.3 Tetracyclin vs tetracyclin + fosfomycin | 1 | 38 | Risk Ratio (M-H, Fixed, 95% CI) | 1.31 [0.76, 2.25] |
Comparison 7 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab), Outcome 1 Cure.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Penicillin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 8 Non-bullous impetigo: oral (Or) antibiotics (Ab) vs placebo (P), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 6 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Cephalexin vs penicillin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.2 Cephalexin vs erythromycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.3 Cephalexin vs azithromycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.4 Cefaclor vs azithromycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.5 Cefaclor vs amoxicillin/clavulanic acid | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.6 Cefadroxil vs penicillin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.7 Cefadroxil vs flucloxacillin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 9 Non-bullous impetigo: oral (Or) antibiotic (Ab) (cephalosporin) vs another oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 7 | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Cephalexin vs cefadroxil | 1 | 96 | Risk Ratio (M-H, Fixed, 95% CI) | 0.99 [0.88, 1.12] |
| 1.2 Cephalexin vs cefdinir | 3 | 201 | Risk Ratio (M-H, Fixed, 95% CI) | 0.95 [0.88, 1.03] |
| 1.3 Cefaclor vs cefdinir | 1 | 13 | Risk Ratio (M-H, Fixed, 95% CI) | 0.64 [0.23, 1.82] |
| 1.4 Cefditoren vs cefuroxime | 1 | 58 | Risk Ratio (M-H, Fixed, 95% CI) | 0.73 [0.55, 0.97] |
| 1.5 Cefditoren vs cefadroxil | 1 | 74 | Risk Ratio (M-H, Fixed, 95% CI) | 1.02 [0.78, 1.33] |
Comparison 10 Non-bullous impetigo: oral (Or) cephalosporin vs other oral (Or) cephalosporin, Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 7 | 363 | Risk Ratio (M-H, Fixed, 95% CI) | 1.06 [0.98, 1.15] |
| 1.1 Erythromycin vs penicillin V | 2 | 79 | Risk Ratio (M-H, Fixed, 95% CI) | 1.29 [1.07, 1.56] |
| 1.2 Erythromycin vs dicloxacillin | 1 | 58 | Risk Ratio (M-H, Fixed, 95% CI) | 1.03 [0.94, 1.13] |
| 1.3 Erythromycin vs amoxicillin | 1 | 129 | Risk Ratio (M-H, Fixed, 95% CI) | 1.00 [0.89, 1.13] |
| 1.4 Azithromycin vs cloxacillin | 1 | 16 | Risk Ratio (M-H, Fixed, 95% CI) | 1.4 [0.57, 3.43] |
| 1.5 Azithromycin vs flucloxacillin/dicloxacillin | 1 | 39 | Risk Ratio (M-H, Fixed, 95% CI) | 0.84 [0.61, 1.16] |
| 1.6 Clindamycin vs dicloxacillin | 1 | 42 | Risk Ratio (M-H, Fixed, 95% CI) | 1.01 [0.80, 1.27] |
Comparison 11 Non-bullous impetigo: oral (Or) macrolide vs penicillin, Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Azithromycin vs erythromycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 12 Non-bullous impetigo: oral (Or) macrolide vs another oral (Or) macrolide, Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 4 | Risk Ratio (M-H, Random, 95% CI) | Subtotals only | |
| 1.1 Amoxicillin + clavulanic acid vs amoxicillin | 1 | 44 | Risk Ratio (M-H, Random, 95% CI) | 1.4 [1.04, 1.89] |
| 1.2 Amoxicillin + clavulanic acid vs fleroxacin | 1 | 42 | Risk Ratio (M-H, Random, 95% CI) | 1.14 [0.80, 1.62] |
| 1.3 Cloxacillin vs penicillin | 2 | 166 | Risk Ratio (M-H, Random, 95% CI) | 1.59 [1.21, 2.08] |
Comparison 13 Non-bullous impetigo: oral (Or) penicillin vs other oral (Or) antibiotic (Ab) (including penicillin), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 2 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Lomefloxacin vs norfloxacin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.2 Fusidic acid vs pristinamycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 14 Non-bullous impetigo: other comparisons of oral (Or) antibiotics (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Penicillin vs hexachlorophene | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 15 Non-bullous impetigo: oral (Or) antibiotics (Ab) vs disinfecting treatments (Dt), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cured/improved after 3 to 4 days | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Eksalb vs placebo | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 16 Bullous impetigo: topical (Top) antimicrobial vs placebo (P), Outcome 1 Cured/improved after 3 to 4 days.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Fusidic acid vs neomycin/bacitracin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.2 Fusidic acid vs chloramphenicol | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] | |
| 1.3 Chloramphenicol vs neomycin/bacitracin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 17 Bullous impetigo: topical (Top) antibiotic (Ab) vs another topical (Top) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only | |
| 1.1 Fusidic acid vs erythromycin | 1 | 24 | Risk Ratio (M-H, Fixed, 95% CI) | 1.43 [0.83, 2.45] |
| 1.2 Neomycin/bacitracin vs erythromycin | 1 | 24 | Risk Ratio (M-H, Fixed, 95% CI) | 0.14 [0.02, 0.99] |
| 1.3 Chloramphenicol vs erythromycin | 1 | 24 | Risk Ratio (M-H, Fixed, 95% CI) | 0.29 [0.07, 1.10] |
Comparison 18 Bullous impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Cephalexin vs dicloxacillin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 19 Bullous impetigo: oral (Or) antibiotic (Ab) vs another oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Mupirocin calcium vs cephalexin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 20 Secondary impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Betamethasone vs gentamycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 21 Secondary impetigo: steroid (S) vs antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Betamethasone + gentamycin vs betamethasone | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 22 Secondary impetigo: steroid (S) + antibiotic (Ab) vs steroid (S), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Betamethasone + gentamycin vs gentamycin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 23 Secondary impetigo: steroid (S) + antibiotic (Ab) vs antibiotic (Ab), Outcome 1 Cure/improvement.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Cure/improvement | 1 | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected | |
| 1.1 Cephalexin vs enoxacin | 1 | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
Comparison 24 Secondary impetigo: oral (Or) antibiotic (Ab) vs another oral (Or) antibiotic (Ab), Outcome 1 Cure/improvement.
#1(impetig* or pyoderma ):ti
#2MeSH descriptor Impetigo explode all trees in MeSH products
#3(#1 OR #2)
#4SR-SKIN in All Fields in all products
#5(#3 AND NOT #4)
1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. clinical trials as topic.sh.
6. randomly.ab.
7. trial.ti.
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. (animals not (human and animals)).sh.
10. 8 not 9
11. exp Staphylococcal Infections/ or stapylococcal skin infections.mp.
12. impetigo.mp. or exp Impetigo/
13. exp Pyoderma/ or pyoderma.mp.
14. 11 or 13 or 12
15. 10 and 14
1. random$.mp.
2. factorial$.mp.
3. (crossover$ or cross-over$).mp.
4. placebo$.mp. or PLACEBO/
5. (doubl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
6. (singl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
7. (assign$ or allocat$).mp.
8. volunteer$.mp. or VOLUNTEER/
9. Crossover Procedure/
10. Double Blind Procedure/
11. Randomized Controlled Trial/
12. Single Blind Procedure/
13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12
14. impetigo.mp. or exp IMPETIGO/
15. exp PYODERMA/ or pyoderma.mp.
16. exp Staphylococcus Aureus/ or stapylococcus aureus.mp.
17. 16 or 15 or 14
18. 13 and 17
((Pt RANDOMIZED CONTROLLED TRIAL OR Pt CONTROLLED CLINICAL TRIAL OR Mh RANDOMIZED CONTROLLED TRIALS OR Mh RANDOM ALLOCATION OR Mh DOUBLE-BLIND METHOD OR Mh SINGLE-BLIND METHOD OR Pt MULTICENTER STUDY) OR ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw clinic$)) AND NOT ((CT ANIMALS OR MH ANIMALS OR CT RABBITS OR CT MICE OR MH RATS OR MH PRIMATES OR MH DOGS OR MH RABBITS OR MH SWINE) AND NOT (CT HUMAN AND CT ANIMALS)) [Palavras] and (impetigo or pyoderma or piodermia or piodermitis or (staphyloccus aureus) or estafilococo) [Palavras]
| Date | Event | Description |
|---|---|---|
| 9 June 2015 | Amended | Author information (affiliation) updated |
| Date | Event | Description |
|---|---|---|
| 7 March 2012 | Amended | The lead author's contact details have been updated. |
| 8 November 2011 | New citation required but conclusions have not changed | A substantial amount of new information has been added in the form of 12 newly included studies. |
| 8 November 2011 | New search has been performed | New search for studies |
| 29 July 2011 | Feedback has been incorporated | In response to peer reviewers' comments, the following major changes were implemented: (1) removed sumscore for risk of bias items; (2) dropped intention to treat analysis as separate risk of bias item; (3) provided more precise information on subjective assessment of symptoms; (4) made a separate table for adverse events. |
| 4 August 2010 | Amended | When finalizing the update, new searches were run (2009-July 2010), resulting in the addition of eight papers to the list of Studies awaiting assessment. |
| 23 February 2009 | New citation required and conclusions have changed | New search (2002-2008), 12 new trials found, one trial previously included discarded. Tables with outcomes of methodological assessments replaced by 'Risk of bias' tables. New author added. |
| 3 October 2008 | Amended | Converted to new review format. |
| 2 September 2004 | New search has been performed | Minor update |
| 4 January 2003 | Amended | New studies found but not yet included or excluded |
| 27 November 2002 | New citation required and conclusions have changed | Substantive amendment |
Conceiving the review - SK, JCvdW, and LvSS
Designing the review - SK, JCvdW, LvSS, CCB, and AM
Co-ordinating the review - SK and JCvdW
Data collection for the review - SK, JCvdW, and RvdS
Developing the search strategy - JCvdW
Undertaking searches - JCvdW, SK, and RvdS
Screening search results - JCvdW, SK, and RvdS
Organising retrieval of papers - JCvdW, SK, and RvdS
Screening retrieved papers against inclusion criteria - LvSS, SK, and RvdS
Appraising quality of papers - JCvdW, AV, and RvdS
Abstracting data from papers - CCB, AM, RvdS, and JCvdW
Writing to trial authors of papers for additional information - SK, RvdS, and JCvdW
Obtaining and screening data on unpublished studies - JCvdW, SK, and RvdS
Data management for the review - SK, RvdS, and JCvdW
Entering data into RevMan - SK, JCvdW, and RvdS
Analysis of data - SK, RvdS, and JCvdW
Interpretation of data - all authors
Providing a methodological perspective - JCvdW
Providing a clinical perspective - SK and CCB
Providing a policy perspective - SK and CCB
Writing the review - SK, RvdS, and JCvdW
Providing general advice on the review - all authors
Securing funding for the review - JCvdW
Performing previous work that was the foundation of current study - LvSS, JCvdW, and SK
Three authors of this review are authors of one included trial (Sander Koning, Lisette WA van Suijlekom-Smit, Johannes C van der Wouden; Koning 2003).
Sander Koning and Johannes C van der Wouden were also involved in a second trial (Koning 2008), which was initiated by the manufacturer of the drug. As employees of Erasmus MC, Rotterdam, Johannes C van der Wouden and Sander Koning received research funding from GlaxoSmithKline for participating in a study comparing retapamulin to placebo in participants with impetigo. The funding was used to pay staff involved in field work. They were also involved in publishing the results. The study was included in the update of this review.
Department of General Practice, Erasmus MC - University Medical Center Rotterdam, Netherlands.
No sources of support supplied
In case of studies assessing cure at more than one point in time, the protocol did not specify what time point to select for data extraction. From the start of the review, we chose the assessment that was closest to one week from the start of treatment.
For this update, the scoring of methodological quality was changed into the newly recommended 'Risk of bias' table (Higgins 2008).We also used risk ratio as recommended by the Cochrane Skin Group.
Industry sponsorship or organisation of the trial was declared to be present in 20 trials (29%): 5 mupirocin studies (Goldfarb 1988; Mertz 1989; Rist 2002; Wainscott 1985; White 1989), 2 with cefdinir (Tack 1997; Tack 1998), 2 with cefadroxil (Beitner 1996; Hains 1989), 2 with azithromycin (Daniel 1991a; Daniel 1991b), 2 with cefditoren (Bucko 2002a; Bucko 2002b); 2 with retapamulin (Koning 2008; Oranje 2007); 1 of amoxicillin plus clavulanic acid (Jaffe 1985), cefalexin (Dillon 1983; Giordano 2006), clindamycin (Blaszcyk 1998), and fusidic acid (Sutton 1992). Five trials (9%) were supported by other organisations. In the remaining 48 (67%) trials, no statement of sponsorship or funding was made (see Table 2 'Declared sponsorship or funding').
| Study | Sponsor (product) |
| Barton 1987 | Fleur de Lis Foundation |
| Barton 1988 | Warner-Lambert Corporation |
| Barton 1989 | Warner- Lambert Corporation |
| Beitner 1996 | Bristol-Myers Squibb (cefadroxil) |
| Blaszcyk 1998 | Pharmacia & Upjohn Asia (clindamycin) |
| Britton 1990 | US Navy Bureau of Medicine and Surgery Clinical Investigation Program |
| Bucko 2002a, Bucko 2002b | TAF Pharmaceutical Products (cefditoren) |
| Daniel 1991a; Daniel 1991b | Pfizer Central Research (azithromycin) |
| Dillon 1983 | Eli Lilly Research (cephalexin) |
| Giordano 2006 | Abott Laboratories (cefdinir) |
| Goldfarb 1988 | Beecham Laboratories (mupirocin) |
| Hains 1989 | Bristol-Myers Squibb (cefadroxil) |
| Jaffe 1985 | Beecham Laboratories (amoxicillin+clavulanic acid) |
| Koning 2003 | Dutch College of General Practitioners |
| Koning 2008 | GlaxoSmithKline (retapamulin) |
| Mertz 1989 | Beecham Laboratories (mupirocin) |
| Oranje 2007 | GlaxoSmithKline (retapamulin) |
| Rist 2002 | GlaxoSmithKline (mupirocin) |
| Sutton 1992 | Leo Laboratories (fusidic acid) |
| Tack 1997 | Parke-Davis pharmaceutical research (cefdinir) |
| Tack 1998 | Parke-Davis pharmaceutical research (cefdinir) |
| Wainscott 1985 | Beecham Pharmaceuticals (mupirocin) |
| White 1989 | Beecham Pharmaceuticals (mupirocin) |
| Methods | Time NR; Japan; range of infections (impetigo 13/265) | |
| Participants |
| |
| Interventions | A: cefdinir 100 mg, 3 td B: cefaclor 250 mg, 3 td | |
| Outcomes | Outcomes of the trial 1) 10 days, excellent/good/poor | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available in the abstract. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available in the abstract. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "....double-blind." Comment: There was unclear blinding of the outcome assessor and caregiver. The participant was probably blinded (see also Figure 2). The test drug packages also included placebo capsules. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 35/300 participants were omitted in the analysis: 16/147 in the cefdinir group (8 due to no or delayed visit to hospital, others for several reasons), 19/153 in the cefaclor group (8 due to no or delayed visit to hospital, others for several reasons) (see table 2). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. |
| Randomised? | Unclear risk | Insufficient information was available in the abstract. |
| Were both inclusion and exclusion criteria specified? | Unclear risk | Insufficient information was available in the abstract. |
| Methods | Time NR; Japan; range of skin infections (including impetigo 18/259) | |
| Participants |
| |
| Interventions | A: lomefloxacin 200 mg, 3 td B: norfloxacin 200 mg, 3 td | |
| Outcomes | Outcomes of the trial 1) 7 days, cured/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available in the abstract. |
| Allocation concealment (selection bias) | Unclear risk | This was unclear. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...a double-blind clinical trial." It was unclear who was blinded (and how). The outcome assessor and caregiver were probably not blinded. The participant was probably blinded (see Figure 1 Dosing schedule). |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | 33/291 participants were omitted in the analysis: 15/147 in the NY-198 group, 17/144 in the norfloxacin group. There was insufficient information in the abstract and figures. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. |
| Randomised? | Low risk | Quote: "...were randomly allocated to one of the two drugs." |
| Were both inclusion and exclusion criteria specified? | Unclear risk | Inclusion (quote): "...skin and soft tissue infections, patients > 15 years". There was no exclusion criteria. |
| Methods | Time NR; Mexico city, Mexico; range of skin infections (including impetigo 55/61) | |
| Participants |
| |
| Interventions | A: mupirocin ointment 2%, 3 td, 5 to 10 days B: dicloxacillin 250 mg, 4 td, 5 to 10 days | |
| Outcomes | Outcomes of the trial 1) 10 days, cure | |
| Notes | Open trial | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | This was not mentioned in the article. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "In an open trial..." Participants received capsules or ointment. Neither the participant, caregiver, nor outcome assessor were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 3/61 participants were omitted in the analysis: 2/29 in the mupirocin group, 1/32 in the dicloxacillin group. Reasons for being non-evaluable for clinical outcome were not specified (but this was a small %). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | High risk | Baseline imbalance: more severe impetigo in the mupirocin group (9/32 vs 3/29, Table 1). There was no data on compliance. |
| Randomised? | Low risk | Quote: "After obtaining informed consent, patients were randomly divided into two treatment groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...pediatric patients with skin infections of sufficient severity to require treatment with a antibiotic." Quote: "Patients who...were excluded from the trial." |
| Methods | June to August 1986; Missouri, USA; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: penicillin V 50 mg/kg/day in 4 dd, 10 ds B: erythromycin 40 mg/kg/day in 4 dd, 10 ds | |
| Outcomes | Outcomes of the trial 1) 7 days, failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available about sequence generation. |
| Allocation concealment (selection bias) | Low risk | Quote: "The patients were assigned to receive either erythromycin or penicillin in a random, double-blind fashion by a pharmacist." Comment: Participants and investigators enrolling participants could not foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | See above - it was not specified how this was done. It is unclear whether the caregiver, participant, or outcome assessor was blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 42/71 participants were omitted in the analysis - reasons and numbers were not specified for each group (6 due to negative culture, 21 not evaluable for effectiveness (not further specified), 6 due to no ascertained compliance, 3 due to no growth of S. aureus alone, 6 withS. aureus alone but not available for follow-up). 14 were left for analysis in the erythromycin group and 15 in the penicillin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Compliance and baseline comparability was unclear. |
| Randomised? | Low risk | Quote: "The patients were assigned to receive either erythromycin or penicillin in a random, double-blind fashion by a pharmacist." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "All patients examined in the outpatient department between June and August 1986 with primarily non bullous impetigo were asked to participate in the study if they were not receiving antibiotics at the time of being seen at CGH, had not taken antibiotics during the preceding week..." |
| Methods | June to August 1987; Missouri, USA; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: erythromycin 40 mg/kg/day in 4 dd, 10 ds B: dicloxacillin 25 mg/kg /day in 4 dd, 10 ds | |
| Outcomes | Outcomes of the trial 1) 5 to 7 days, cure + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "Participants were randomly assigned in a double-blind manner by the hospital pharmacist to receive..." Hence, participants and investigators enrolling participants could not foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | See above - not specified how and who was blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 41/100 participants were omitted in analysis - not specified for each group (12/100 were lost to follow up, but not stated from which group). 29 were left in the erythromycin group and 30 left in the dicloxacillin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Group assignment of non-compliant participants was unclear. |
| Randomised? | Low risk | Quote: "Participants were randomly assigned in a double-blind manner by the hospital pharmacist to receive..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "During the months of June, July and August, 1987, 100 children with impetigo, from whom informed consent was obtained, were consecutively enrolled in the study." Quote: "Exclusion criteria included..." |
| Methods | June to August 1988; Missouri, USA; outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | A: erythromycin 40 mg/kg/day in 3 dd, 7 days B: mupirocin ointment 2%, 3 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 4 to 7 days, cured + improved | |
| Notes | 14% bullous | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | This was not mentioned in the article. |
| Blinding (performance bias and detection bias) patient | High risk | Participant and caregiver were not blinded because they received either capsules or ointment. It is not mentioned in the article whether the outcome assessor was blinded (probably not, because the caregiver and participant were not blinded) |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 1(/97) participant was omitted in the analysis, specified: 1/48 in the erythromycin group (lost to follow up), 0/49 in the mupirocin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Compliance was not reported. |
| Randomised? | Low risk | Quote: "Participants were randomly assigned to receive either..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children over 6 weeks of age with a clinical diagnosis of impetigo were invited to participate in the study. Exclusion criteria included..." |
| Methods | Time NR; Honolulu, Hawaii; hospital outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | 3 arms: A: cephalexin 50 mg/kg/day in 3 dd + placebo ointment, 10 days B: mupirocin ointment 2%, 3 td + liquid oral placebo C: bacitracin ointment 500 units/g, 3 td + liquid oral placebo | |
| Outcomes | Outcomes of the trial 1) 8 to 10 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "...clinical pharmacist assigned them by a table of random numbers to one of the three treatment groups". |
| Allocation concealment (selection bias) | Low risk | See above and the quote: "The clinician, patients and their parents were not aware of which of the three treatment regimens they were assigned." Comment: Central allocation - participants and investigators enrolling participants could not foresee assignment. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "The clinician, patients and their parents were not aware of which of the three treatment regimens they were assigned." Comment: The outcome assessor, participant, and caregiver were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 6/32 participants were omitted in the analysis: 0/10 in the cephalexin group, 5/12 in the mupirocin group, 1/10 in the bacitracin group (missing Imbalance for missing data). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was a baseline imbalance for size and type of lesion. Compliance was assessed in only 17 participants. |
| Randomised? | Low risk | Quote: "...clinical pharmacist assigned them by a table of random numbers to one of the three treatment groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quoted from the referred article Demidovich: "Children presenting with impetigo to our clinic were eligible for the study. Exclusion criteria were..." |
| Methods | December 1992 to November 1994; 25 centres, Sweden; outpatients; range of skin infections (impetigo 60/327) | |
| Participants |
PE | |
| Interventions | A: cefadroxil 40 mg/kg/day, 10 days B: flucloxacillin tablets 750 mg, 2 td, or susp 30 to 50 mg/kg/day in 2 to 3 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 10 to 12 days, cure/improved/failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | The method of concealment was not described. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...single blinded." Quote: "Statistical analysis was performed blinded." Comment: The participant, outcome assessor, and caregiver were probably not blinded because participants in both groups did not receive the same administrations of study drugs daily. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 334/661 participants were missing mainly due to a lack of a bacterial culture sensitive to both drugs, and 351/661 were omitted from the primary analysis. 33 impetigo participants were included in the primary analysis. Exact reasons for not being evaluable and group assignment were not reported. 19/661 were omitted in the "ITT-analysis". |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "The randomization produced two comparable groups of patients with no differences in known prognostic factors." Comment: There was no compliance data. |
| Randomised? | Low risk | Quote: "In this prospective single-blind comparative and randomized multicentre trial..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Table 1: Inclusion and exclusion criteria for the subjects participating in the study. |
| Methods | Period NR; multicentre; Europe, Latin America, Asia; range of skin infections (impetigo 42/539) | |
| Participants |
PNE | |
| Interventions | A: clindamycin caps 150 mg, 4 td B: clindamycin caps 300 mg, 2 td C: dicloxacillin caps 250 mg, 4 td | |
| Outcomes | Outcomes of the trial 1) 7 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Drug supplies were masked." Comment: Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "Drug supplies were masked." Quote: "Patients in all groups received four administrations of study drugs daily." Comment: The outcome assessor, participant, and caregiver were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 48/588 were omitted in the analysis: 16/196 in the clindamycin caps 150 mg group, 19/198 in the clindamycin caps 300 mg group, 20/194 in the dicloxacillin caps group. Proportions of participants who did not complete the study medication and reasons were ˜ similar (table II). There were not only impetigo participants. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Compliance data was provided (table II) and well-balanced. The distribution of baseline characteristics was not provided. |
| Randomised? | Low risk | Quote: "This prospective, double mask, randomized study..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients were selected based on..." Quote: "Patients were ineligible if..." |
| Methods | October 1988 to October 1989; Portsmouth, Virginia, USA; outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | A: erythromycin 40 mg/kg/day in 4 dd + placebo cream B: mupirocin ointment 2%, 3 td + placebo susp | |
| Outcomes | Outcomes of the trial 1) 10 days, cured + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups." |
| Allocation concealment (selection bias) | Low risk | Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups." Comment: central allocation - pharmacy-controlled. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "The child group assignment was not known to parents or investigators." Quote: "...assigned each patient to one of two groups: orally administered erythromycin plus topically applied placebo (erythromycin group) or orally administered placebo plus topically applied mupirocin (mupirocin group)." Comment: The outcome assessor, participant, and caregiver were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 6/54 participants were omitted in the analysis: 2/24 in the mupirocin group, 4/30 in the erythromycin group. Participants not completing the study were left out of the analysis. Reasons for not completing the study were not specified for each group. 3 were lost to follow up, 2 dropped out when misdiagnosis was suspected, and 1 was removed because of S. pyogenes pharyngitis. < 20% withdrawals and numbers were balanced. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | High risk | Baseline characteristics were imbalanced (sex, severity), and compliance was also skewed. |
| Randomised? | Low risk | Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children aged 12 years and younger with the clinical diagnosis of impetigo..." Quote: "We excluded..." |
| Methods | Unlear, around 2000; US, multicentre; ambulatory setting; range of skin infections (including impetigo 58/857) | |
| Participants |
PNE | |
| Interventions | A: cefditoren 200 mg, 2 td, 10 days B: cefditoren 400 mg, 2 td, 10 days C: cefuroxime 250 mg, 2 td, 10 days | |
| Outcomes | Outcomes of the trial 1) 7 to 14 days, cured or improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not reported. |
| Allocation concealment (selection bias) | Low risk | Quote: "Study-drug containers were dispensed in numeric sequence at each investigative site as patients were enrolled to ensure random assignment." |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "...double-blind, double-dummy..." Quote: "Patients' evaluability and outcomes were assessed under blinded conditions". The outcome assessor, caregiver, and participant were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | For only impetigo: 2/58 missing impetigo participants in total - 0/19 in the cefditoren 200 mg group, 2/21 in the cefditoren 400 mg group, 0/18 in the cefuroxime 250 mg group. Reasons for missing participants were not specified (but a small % were non-evaluable) |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no compliance data and no baseline imbalance. |
| Randomised? | Low risk | Quote: "Patients were randomized." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Eligible patients included..." Quote: "Study exclusion criteria included..." |
| Methods | Unclear, around 2000; US; multicentre; ambulatory setting; range of skin infections (including impetigo 74/828) | |
| Participants |
PNE | |
| Interventions | A: Cefditoren 200 mg, 2 td, 10 days B: Cefditoren 400 mg, 2 td, 10 days C: Cefadroxil 500 mg, 2 td, 10 days | |
| Outcomes | Outcomes of the trial 1) 7 to 14 days, cured or improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not reported. |
| Allocation concealment (selection bias) | Low risk | Quote: "Study-drug containers were dispensed in numeric sequence at each investigative site as patients were enrolled to ensure random assignment." |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "...double-blind, double-dummy..." Quote: "Patients' evaluability and outcomes were assessed under blinded conditions". Comment: The outcome assessor, caregiver, and participant were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | For only impetigo: 4/74 missing participants - 1/27 in the cefditoren 200 mg group, 0/25 in the cefditoren 400 mg group, 3/22 in the cefadroxil 500 mg group. Reasons for missing participants were not specified (but a small % were non-evaluable) |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no compliance data and no baseline imbalance. |
| Randomised? | Low risk | Quote: "Patients were randomized..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Eligible patients included..." Quote: "Study exclusion criteria included..." |
| Methods | Time NR; Sweden, Germany, UK; Outpatients (Germany) and GP (UK), both (Sweden); only impetigo | |
| Participants |
PE | |
| Interventions | A: hydrogen peroxide cream 1% (Microcid), 2 to 3 td, max 21 days B: fusidic acid cream gel 2%, 2 to 3 td, max 21 days | |
| Outcomes | Outcomes of the trial 1) evaluation time NR, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "...randomized (in blocks of four)." The process for selecting the blocks was not specified. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "The tubes were put into identical paper boxes, to keep the trials blind." Comment: Insufficient information was available. The tubes may have been different. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "The tubes were put into identical paper boxes, to keep the trials blind." There was incomplete blinding - participants were probably not blinded (see above), and blinding with regard to the outcome assessor and caregiver is unclear. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 135/391 participants were omitted in the analysis because they were culture negative (not specified per group); 11/156 participants in the M-group and 3/156 in the F-group were withdrawn due to deterioration of their impetigo (statistically significant), 3/156 in the F-group and 0/156 in the M-group were withdrawn due to adverse events (irritation of the skin, burning, and blistering). All participants fulfilling the prespecified requirement of bacteriologically-verified impetigo were analysed. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no data on baseline comparability and compliance. |
| Randomised? | Low risk | Quote: "...randomized (in blocks of four)." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were included" Quote: "Patients were not allowed... prior to start of study..." |
| Methods | 1999; Turkey; hospital outpatient department; only impetigo | |
| Participants |
| |
| Interventions | A: topical mupirocin 2% 3td for 10 days B: topical terbinafine 1% 3td for 10 days | |
| Outcomes | Outcomes of the trial 1) 10 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...mupirocin group was instructed to use Bactroban 2% ointment and terbinafine group was instructed to use Lamisil 1% cream topically three times daily for ten days". The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 14/62 participants were not analysed: 6/31 were missing in the mupirocin group, 8/31 were missing in the terbinafine group. Quote: "At the end of the treatment, 25 participants in the mupirocin group and 23 participants in the terbinafine group were considered eligible" . > 20% missing. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | High risk | Quote: "The group had similar features except for the time from appearance of lesions to hospital admission." There was a mean of 5.44 in the mupirocin group versus 6.78 in the terbinafine group. |
| Randomised? | Low risk | Quote: "...in a randomized fashion." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were excluded." Quote: "....children, less than 12 years old, presenting with impetigo to..." |
| Methods | Time NR; France; ambulatory setting (dermatology outpatient departments); range of skin infections (including impetigo 53/334) | |
| Participants |
| |
| Interventions | A: oral fusidic acid 2 x 250 mg 2 td for 7.5 days B: oral pristinamycin 2 x 500 mg 2 td for 10 days | |
| Outcomes | Outcomes of the trial 1) 11 days, cured and improved | |
| Notes | Outcome data for impetigo participants was provided by the author (personal communication). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Afin de garantir le double insu, chaque patient recevait le traitement dont 2.5 jours de placebo". [To ensure double blinding, each patient received a placebo for 2.5 days]. The participants were blinded, but blinding is unclear with regard to the caregiver and outcome assessor. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 313/334 participants were analysed (< 10% not in analysis). There is no data for impetigo participants. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data and no baseline comparison. |
| Randomised? | Low risk | Quote: "Une etude multicentrique, prospective, randomisée..." [A randomised, prospective, multicentre study...] |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Tout patient ambulatoire, âgé de plus de 18 ans, avec une pyodermite superficielle nécessitant une antibiothérapie orale et ayant donné son consentement éclairé pouvait être inclus dans l'essai à condition de ne presenter aucun des critères d'exclusion suivants." [Most ambulatory participants, older than the 18 years old, with a superficial pyoderma requiring oral antibiotics and with given informed consent could be included in the study provided there were none of the following exclusion criteria present.] |
| Methods | May to October 1987; Negev region, Israel; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: amoxicillin trihydrate syrup 40 mg/kg/day, in 3 dd, 10 days B: amoxicillin/clavulanic acid syrup 40 + 10 mg/kg/day, in 3 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 5 days, cure + improved | |
| Notes | There was missing data from the first follow-up measurement for 4/26 participants in the amoxicillin trihydrate syrup group and 3/25 participants in the amoxicillin/clavulanic acid syrup group. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...in a double-blind fashion". It is unclear whether the outcome assessor, participant, or caregiver were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 7/52 (< 20%) participants were omitted in the analysis after 5 days. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | High risk | There was a baseline imbalance for lymphadenopathy > 20%. There were no compliance data. |
| Randomised? | Low risk | Quote: "After obtaining the cultures, patients were randomized to..." |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "We included..." Exclusion criteria was not mentioned. |
| Methods | July 1989 to October 1990; Negev region, Israel; outpatients; only impetigo (bullous and non-bullous) | |
| Participants |
PNE | |
| Interventions | A: erythromycin susp 50 mg/kg/day 3 td + placebo ointment, 7 days B: mupirocin ointment 2% 3 td + oral placebo susp, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "The randomized code was prepared by Beecham Pharmaceutical and was not known to the investigators until after the raw data were tabulated." |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "The randomized code was prepared by Beecham Pharmaceutical and was not known to the investigators until after the raw data were tabulated." The erythromycin group received a placebo ointment and the mupirocin group received an oral placebo suspension. The outcome assessor, caregiver, and participant were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 13/102 participants were omitted in the analysis: 8/51 in the erythromycin group (1 due to side-effects, 7 due to refusal to continue treatment or to return for the follow-up visit), 5/51 missing in the mupirocin group (all due to refusal to continue treatment or to return for the follow-up visit). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were age and sex differences at baseline (table 1), although they were not significant. There were no compliance data. |
| Randomised? | Low risk | Quote: "...were randomized into two groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Infants... were enrolled." Quote: "Excluded groups were..." |
| Methods | 1987 to 1991; Belgium, France, FRG, Netherlands, Norway, UK; setting unclear; range of skin infections (including impetigo 69/308) | |
| Participants |
PNE | |
| Interventions | A: azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days B: erythromycin 500 mg 4 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 11 to 16 days, cured | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were allocated to treatment with azithromycin or erythromycin in a 1:1 ratio using a randomization list." |
| Allocation concealment (selection bias) | Unclear risk | See above - it is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor was likely to also be the caregiver, so probably all 3 were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | The number of impetigo participants not included in analysis was small and well-balanced (1 vs 2). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data. Baseline characteristics were well-balanced. |
| Randomised? | Low risk | Quote: "Patients were allocated to treatment with azithromycin or erythromycin in a 1:1 ratio using a randomization list." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "In order to be included..." Quote: "Exclusion criteria were..." |
| Methods | 1987 to 1989; Belgium, Germany, Ireland, UK; setting unclear; range of skin infections (including impetigo 17/323) | |
| Participants |
PNE | |
| Interventions | A: azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days B: cloxacillin 500 mg, 4 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 11 to 16 days, cured/improved/failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Using a presupplied randomization list patients were allocated to receive azithromycin or cloxacillin in the ratio of 2:1." |
| Allocation concealment (selection bias) | Unclear risk | See above - it is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Only 1 impetigo participant was not in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data. Baseline characteristics were comparable. |
| Randomised? | Low risk | Quote: "Using a presupplied randomization list patients were allocated to receive azithromycin or cloxacillin in the ratio of 2:1." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "In order to be included..." Quote: "Exclusion criteria were..." |
| Methods | Time NR; Honolulu, Hawaii; outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | A: penicillin V 40 to 50 mg/kg/day in 3 dd, 10 days B: cephalexin 40 to 50 mg/kg/day in 3 dd, 10 days C: erythromycin 30 to 40 mg/kg/day in 3 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 8 to 10 days, failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "The pharmacist randomly assigned them to one of three treatment regimens." Central allocation - participants could not foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Patients were reevaluated...by one of the authors, both of whom were blinded to the treatment each child was receiving." Comment: Participants were probably not blinded. The caregiver and outcome assessor were probably blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 2/75 participants were omitted in the analysis: 2 participants were lost to follow up (not further specified). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "There was not a significant difference in disease severity among treatment groups." Compliance in both groups was comparable, but low. |
| Randomised? | Low risk | Quote: "The pharmacist randomly assigned them to one of three treatment regimens." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children presenting with impetigo to our pediatric clinic were eligible for the study. Exclusion criteria were..." |
| Methods | 1980 summer/fall; Alabama, USA; outpatients; only impetigo (bullous impetigo 57/70) | |
| Participants |
PNE | |
| Interventions | A: cephalexin 50 mg/kg/day in 2 dd (> 20 kg: 500 mg 2 td) B: dicloxacillin 15 mg/kg/day in 4 dd (> 40 kg: 125 mg 4 td) | |
| Outcomes | Outcomes of the trial 1) Prompt cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomly assigned, according to a standard table, to receive..." (Referring to a standard table.) |
| Allocation concealment (selection bias) | Unclear risk | See above - it is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 8/78 participants were omitted in the analysis: 5 vs 3 participants failed to return or, with a negative culture, were not included in the analysis (< 20% and balanced). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "Preference was given to patients with skin infections typical of staphylococcal bullous impetigo." Comment: Furthermore, there were no baseline differences, and compliance was not reported. |
| Randomised? | Low risk | Quote: "Patients were randomly assigned, according to a standard table, to receive..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "The criterion for enrolment was..." Quote: "...were excluded." |
| Methods | Time NR; Toronto, Canada; setting unclear; range of skin infections (including impetigo 36/149) | |
| Participants |
PNE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 days B: erythromycin 250 mg, 4 td, 7 days C: cloxacillin 250 mg, 4 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved/failure. Clocacillin: no participants with impetigo allocated | |
| Notes | 2 cases of secondary impetigo, both in the mupirocin group, were excluded from the results presented here. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information about the sequence generation process was available, and there was unexpected distribution (78 vs 50 vs 20). |
| Allocation concealment (selection bias) | Unclear risk | Quote: "...were randomized into two treatment groups by each investigator." Comment: It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...single-blind". Comment: It is not clear who was blinded and how this was done. Also, participants in both groups did not receive the same administrations of study drugs daily. Participants were probably not blinded. The blinding of outcome assessor and caregiver is unclear. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 1 (/149) participant was omitted in the analysis: 1/79 in the mupirocin group due to an infected cyst (not included in analysis), 0/50 in the erythromycin group, 0/20 in the cloxacillin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Compliance was not reported. There was a large age difference between groups (mean 22 vs 31 years), unknown for impetigo participants. |
| Randomised? | Low risk | Quote: "In each section of the study, patients with primary or secondary skin infections were randomized into two treatment groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients with primary and secondary skin infections that were severe enough were included in three parallel-study groups." Quote: "Patient who did not..." |
| Methods | October to November 1983; Puerto Rico; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 to 9 days B: vehicle control, 3 td, 7 to 9 days | |
| Outcomes | Outcomes of the trial 1) 8 days, cure/improved/failure 1 participant with ecthyma was excluded in each group. | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of five per group." |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "...double-blind, vehicle-controlled." Also, participants in both groups received the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 14/52 participants were omitted in the analysis: 8/26 in the mupirocin group (5 were "unavailable for follow-up", 3 for several reasons (specified)), 6/26 in the vehicle group (2 were "unavailable for follow-up", 3 for several reasons (specified)). There were more than 20% withdrawals and dropouts. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. Compliance was not reported. |
| Randomised? | Low risk | Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of five per group." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were admitted to the study." Quote: "Patients were excluded if..." |
| Methods | Time NR; Milwaukee, Wisconsin, USA; outpatients; only impetigo | |
| Participants |
| |
| Interventions | A: mupirocin (dose NR) B: erythromycin (dose NR) | |
| Outcomes | Outcomes of the trial 1) Time of evaluation NR, failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Oral versus topical treatment. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 9/48 participants were omitted in the analysis: 4/25 in the mupirocin group (3 due to "fail to return for follow-up", 1 reason not mentioned), 5/23 in the erythromycin group (3 due to "fail to return for follow-up", 2 reasons not mentioned). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no baseline characteristics per group. There were no compliance data. |
| Randomised? | Low risk | Quote: "...randomized." |
| Were both inclusion and exclusion criteria specified? | High risk | This was not mentioned in the article. |
| Methods | Time NR; Lebanon; outpatients; probably all impetigo ('superificial pyogenic skin infection') | |
| Participants |
| |
| Interventions | A: gentamycin cream 1% 3 td, duration unknown B: neomycin ointment 0.5% 3 td, duration unknown | |
| Outcomes | Outcomes of the trial 1) Cured, improved after 7 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was provided. |
| Allocation concealment (selection bias) | Unclear risk | This was not reported. |
| Blinding (performance bias and detection bias) patient | Unclear risk | This was not reported. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | 11/139 participants were lost to follow up (it was not stated in which group). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was an unexplained imbalance of group size (88 vs. 44). There were no compliance data. There was no baseline comparison. |
| Randomised? | Low risk | Quote: "The persons included in this study were divided into two groups at random." |
| Were both inclusion and exclusion criteria specified? | High risk | Inclusion and exclusion criteria was not specified. |
| Methods | 2002 to 2003; Mali; hospital outpatients; only impetigo | |
| Participants |
| |
| Interventions | A: oral amoxicillin 50 mg/kg/day + topical 10% povidone iodine for 7 days B: oral erythromycin 30 mg/kg/day + topical 10% povidone iodine for 7 days | |
| Outcomes | Outcomes of the trial 1) Proportion cured + improved after 7 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "...using a table of random numbers". Comment: This was an adequate method. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "....an open randomized trial." Quote: "Patients and investigators were not blinded." The outcome assessor, participant, and caregiver were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 3/132 participants were not analysed: 2/66 in the amoxicillin group (2 lost to follow up on the 7th day), 1/66 in the erythromycin group (1 lost to follow up on the 7th day). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline comparison. There were no compliance data. |
| Randomised? | Low risk | Quote: "...an open randomized trial." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients aged more than 1 year old... were considered for inclusion." Quote: "The following cases were excluded..." |
| Methods | Time NR; Japan; outpatients; range of skin infections (including impetigo 10/204) | |
| Participants |
| |
| Interventions | A: enoxacin 500 mg 3 td B: cephalexin 500 mg 2 td (double dummy) | |
| Outcomes | Outcomes of the trial 1) After .... cured/improved | |
| Notes | Secondary impetigo- it only says impetigo above | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not mentioned in the abstract. |
| Allocation concealment (selection bias) | Unclear risk | This was not mentioned in the abstract. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...a double-blind." They used placebo capsules (see Figure 1 Dosage schedule). Participants were probably blinded. It is not clear how, and if, the caregiver and outcome assessor were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | 22/226 participants were omitted in the analysis: 14/115 in the enoxacin group (2 due to exclusion (1 overlap administration and 1 antibiotics before treatment), 12 dropped out (11 shortage of duration, 1 no successive visit)), 8/111 in the cephalexin group (all dropped out (7 shortage of duration, 1 no successive visit). < 20% but not specified for impetigo participants. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance (table 4), and compliance was not reported. |
| Randomised? | Unclear risk | This was not mentioned in the abstract. |
| Were both inclusion and exclusion criteria specified? | Unclear risk | This was not mentioned in the abstract. |
| Methods | Time NR; Quebec, Canada; outpatients; range of skin infections (including impetigo 19/70) | |
| Participants |
PE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 days B: fusidic acid cream 2%, 3 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved/failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | The abstract reported the study was double-blind, but it is not explained in the article. There is unclear blinding of the outcome assessor, caregiver, and participant. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 1 (/70) participant was omitted in the clinical analysis: 0/35 in the fusidic acid group, 1/35 in the mupirocin group. Participants were not examined if pre-treatment cultures were negative or if post-treatment evaluation was not possible. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance, and compliance was not reported. |
| Randomised? | Low risk | Quote: "Patients were randomly divided into two treatment groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients who... were excluded from the trial." Quote: "...in 70 patients who came to the dermatologic clinic with primary and secondary skin infections of sufficient severity to require antibiotic therapy." |
| Methods | Time NR; Dallas, Texas, USA; outpatients; only impetigo | |
| Participants |
Part excluded: unclear | |
| Interventions | A: penicillin G 30 mg/kg/day in 4 dd, duration NR B: cefadroxil 45 mg/kg/day in 3 dd, duration NR | |
| Outcomes | Outcomes of the trial 1) 8 days, cured + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Participants in both groups received different administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 21/71 participants were omitted in the analysis due to failure to return for both follow-up examinations. There were more than 20% withdrawals; this was not further specified for each group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "Groups were comparable with regard to age, sex, race and extent of skin lesion." Compliance was unclear. |
| Randomised? | Low risk | Quote: "Infants and children with impetigo were assigned treatment randomly." |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Infants and children with impetigo were assigned..." No exclusion criteria were specified. |
| Methods | 2005; US; hospital outpatients; skin infections (including impetigo 16/391) | |
| Participants |
| |
| Interventions | A: oral cefdinir 300 mg 2 td 10 days B: cephalexin 200 mg 4 td 10 days | |
| Outcomes | Outcomes of the trial 1) Proportion cured + improved after 17 to 24 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "A computer-generated randomization schedule in a 1:1 ratio was used." Quote: "Study drug containers were dispensed in increasing numerical sequence at each investigative site." |
| Allocation concealment (selection bias) | Unclear risk | Quote: "To maintain investigator blinding, the study drug was dispensed by an unblinded third person who did not participate in the assessments of clinical response." Comment: It is not clear whether this person was involved in participant contacts. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...investigator-blinded." Quote: "To maintain investigator blinding, the study drug was dispensed by an unblinded third person who did not participate in the assessments of clinical response. Furthermore, the participant was instructed not to disclose any details about the study drug (...) to the investigator." The outcome assessor and caregiver were blinded. The participants were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | There were 0/16 missing impetigo participants: 0/4 in the cefdinir group, 0/12 in the cephalexin group. All 391 who took at least 1 dose of the study drug were analysed. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data. There was no baseline comparison. |
| Randomised? | Low risk | Quote: "A computer-generated randomization schedule..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were enrolled" Quote: "Study exclusion criteria included..." |
| Methods | Time NR; Cleveland, Ohio, USA; outpatients; only impetigo | |
| Participants |
PE: NR | |
| Interventions | A: mupirocin ointment 2%, 3 td, 8 days B: erythromycin 40 mg/kg/day in 4 dd, 8 days | |
| Outcomes | Outcomes of the trial 1) 8 days, cured/failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Topical versus oral treatment. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 10/62 participants were lost in total: 5/30 in the mupirocin group (all lost to follow up), 5/32 in the erythromycin group (all lost to follow up). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | The severity of impetigo was not compared between the 2 groups. There was a difference in age (range vs mean). Compliance was not reported. |
| Randomised? | Low risk | Quote: "Enrolled children were randomly assigned to groups that..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children 3 months of age and older were seen at...were eligible for our study." Quote: "Children were excluded if..." |
| Methods | July to September 1980; Florida, USA; outpatients; only impetigo (bullous and non-bullous). | |
| Participants |
Participants were excluded if no S. aureus was present | |
| Interventions | A: penicillin V potassium 50 mg/kg/day, in 4 dd, 10 days B: cloxacillin sodium 50 mg/kg/day, in 4 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 10 days: cured + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "...on a randomized schedule at the following dosages". It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "The clinical examiners were blinded to the antibiotic that the patients received until the study was concluded." Quote: "...double-blind schedule." It is not clear how patients were blinded, and the participant was likely to be influenced in the case of lack of blinding. The outcome assessor and caregiver were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 24/101 participants were lost due to no S. aureus growth, 10 were lost in failure to return to the clinic (reasons for not attending follow-up visit were not stated). The imbalance in participants was not evaluated. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline severity comparison between groups. Participant compliance data was computed and presented no significant alterations in therapeutic outcome. |
| Randomised? | Low risk | Quote: "...on a randomized schedule at the following dosages..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...could be enrolled on the study if the following criteria were met..." Quote: "There were no prior histories of allergic phenomena." |
| Methods | Time NR; Edinburgh, UK; general practice; range of skin infections (including impetigo 39/107) | |
| Participants |
PNE | |
| Interventions | A: mupirocin ointment 2%, once daily, until cleared B: placebo cream, once daily, until cleared | |
| Outcomes | Outcomes of the trial 1) Time of evaluation NR, cure/improved/failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Patients were allocated a trial number in the consecutive order of their entry in the study. The study was performed under double blind conditions. Medication appropriate to the trial number, either mupirocin or placebo ointment, was dispensed according to a pre-determined randomization which ensured that in each group of four patients, two received treatment with mupirocin and two with placebo ointment." The process for selecting the blocks was not specified. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "The study was performed under double-blind conditions." It is unclear whether, and how, the outcome assessor, caregiver, and participant were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | 14/107 participants were omitted in the analysis: 10/54 in the mupirocin group (they were classified as clinically unassessable, 7 did not return for final assessment (5 were traced later and found to have clinically improved), 3 developed other diseases requiring systemic treatment), 4/53 in the placebo group (3 did not return for final assessment (2 of whom were later found to have improved and one worsened and sought alternative treatment), 1 developed other disease requiring systemic treatment). < 20%, 3 vs 1 impetigo participant not evaluable. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "...well matched". There was no compliance data. |
| Randomised? | Low risk | Quote: "...according to a pre-determined randomization." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients with acute primary skin infections...who had not received topical or systemic antibiotics during the preceding 3 days were entered in the study." |
| Methods | Time NR; Montreal, Quebec, Canada; outpatients; range of skin infections (including impetigo 15/60) | |
| Participants |
PE: NR | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 days B: erythromycin 250 mg, 4 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved/failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "...were randomly divided into two treatment groups." It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Topical versus oral treatment. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/60 participants were omitted in the analysis: 0/30 in the mupirocin group, 0/30 in the erythromycin group. 1 participant in the mupirocin group discontinued therapy due to intolerable side-effects. All impetigo participants were included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline data. There were no compliance data. |
| Randomised? | Low risk | Quote: "...were randomly divided into two treatment groups." |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Sixty patients with primary and secondary skin infections were randomly divided." No exclusion criteria was specified. |
| Methods | Summer 1986; Birmingham, Alabama, US; outpatients child hospital; only impetigo | |
| Participants |
PE: NR | |
| Interventions | A: cefadroxil 30 mg/kg/day, max 1 g, in 1 dd, 10 days B: cephalexin 30 mg/kg/day, max 1 g, in 2 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 14 days, cured | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Patients were randomly assigned to receive either..." It is unclear whether participants and investigators enrolling patients could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Participants in both groups received different administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 13/101 participants were omitted in the analysis in total: 4/55 in the cefadroxil group (1 failed to keep all of the appointments, 3 participants failed to take medications as prescribed), 9/54 in the cephalexin group (3 with negative cultures, 4 failed to keep all of the appointments, 2 participants failed to take medications as prescribed). < 20% and reasons described. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was baseline data. Compliance was good in both groups. |
| Randomised? | Low risk | Quote: "Patients were randomly assigned to receive either..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...who had a clinical diagnosis of pyoderma were enrolled." Quote: "Children were excluded if..." |
| Methods | Summer 1976; Tokyo, Japan; hospital outpatient clinic; bullous impetigo | |
| Participants |
| |
| Interventions | A: topical Eksalbe simplex (ointment containing killed escherichia, staphylococcus, streptococcus, and pseudomonas) applied once daily under plaster or 3 times daily without plaster B: placebo | |
| Outcomes | Outcomes of the trial 1) Cured/improved after 4 days | |
| Notes | Data extraction and risk of bias assessment done by Testuri Matsumura. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not reported. |
| Allocation concealment (selection bias) | Low risk | Allocation was concealed (assessed by Tetsuru Matsumura). |
| Blinding (performance bias and detection bias) patient | Low risk | The participant, outcome assessor, and caregiver were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 2/40 participants were dropouts and excluded from the analysis. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data. |
| Randomised? | Low risk | This trial was randomised (assessed by Tetsuru Matsumura). |
| Were both inclusion and exclusion criteria specified? | High risk | Exclusion criteria were not specified. |
| Methods | Time NR; Cleveland, Ohio, USA; outpatients child clinic; range of skin infections (including impetigo 32/42) | |
| Participants |
PNE | |
| Interventions | A: amoxicillin/clavulanic (125/30) acid, dose equivalent to 20 mg amoxicillin/kg/day in 3 dd, 10 days B: cefaclor 20 mg/kg/day in 3 dd | |
| Outcomes | Outcomes of the trial 1) 10 days, cured/failed | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "Prescription were filled by the hospital pharmacist using double-blind labels." Personnel or participants could, probably, not foresee assignment. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "Prescription were filled by the hospital pharmacist using double-blind labels." The outcome assessor, caregiver, and participant were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/43 participants were omitted in the analysis: 0/21 in the amoxicillin/clavulanic acid group, 0/22 in the cefaclor group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Low risk | Quote: "The two treatment groups were generally comparable." Compliance was good in 75% of participants. |
| Randomised? | Low risk | Quote: "Children were randomly assigned to one of the two treatment regimens." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children 6 months to...were eligible for inclusion in the study." Quote: "Exclusion criteria included..." |
| Methods | Time NR; multicentre, Wessex, UK; general practice; range of skin infections (including impetigo 43/119) | |
| Participants |
PNE | |
| Interventions | A: 1% hydrocortisone + 0.5% potassium hydroxyquinoline sulphate cream, 2 td, 14 days B: 1% hydrocortisone + 2% miconazole nitrate cream, 2 td, 14 days | |
| Outcomes | Outcomes of the trial 7 days, cured/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "The trial was double-blind, patients being allocated at random to receive..." Quote: "The randomization was balanced for each centre, with separate randomizations for each of the two indications." It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "Unmarked plain tubes of the marketed formulation of each product were packed in plain sealed cartons, neither doctors nor patients being aware of the identity of the products until the end of the study." Comment: The outcome assessor, caregiver, and participant were probably blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/119 participants were omitted in the analysis: 0/65 in group 1, 0/54 in group 2. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Details of age, duration of condition, and total symptom severity score were recorded and were similar. There were no compliance data. |
| Randomised? | Low risk | Quote: "The trial was double-blind, patients being allocated at random to receive..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...who presented... were included in the study." Exclusion criteria was not specified. |
| Methods | Time NR; Bristol, UK; general practice; only impetigo | |
| Participants |
PNE | |
| Interventions | A: mupirocin ointment 2%, 2 td, 10 to 11 days B: neomycin ointment 1%, 2 td, 10 to 11 days | |
| Outcomes | Outcomes of the trial 1) Time of evaluation NR, cure/improved/failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Quote: "Allocation of treatment was on a randomized basis. In each consecutive group of four patients, two received Bactroban ointment and two received neomycin." Comment: They probably used blocked randomisation, but the process of selecting the blocks was not specified. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "The 15-g tubes differed only in their code numbers and in both cases the content was a white ointment." It is unclear how investigators were blinded. The caregiver and participant were probably blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 9/41 participants were omitted in the analysis: 8 were excluded due to a "stated diagnosis other than uncomplicated impetigo" (not stated which group), 1 missing from the mupirocin group due to "failure to attend to follow-up". |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was baseline imbalance for age (mean 11 vs 17 years). There were no compliance data. |
| Randomised? | Low risk | Quote: "Allocation of treatment was on a randomized basis." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients were selected from those presenting with typical impetigo." Quote: "Patients were excluded if..." |
| Methods | Time NR; multicentre USA (Southern States); admitted + outpatients; range of skin infections (including impetigo 18/179) | |
| Participants |
PE | |
| Interventions | A: azithromycin 500 mg day 1, 250 mg, day 2 to 5, 5 days B: cephalexin 500 mg twice daily, 10 days | |
| Outcomes | Outcomes of the trial 1) 11 days, cured/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "In this double blind..." Quote: "Using a double-dummy technique, each patient received placebo capsules which were visually identical to the active drugs." Comment: The caregiver and participant were probably blinded. There was unclear blinding of the outcome assessor. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 187/366 participants were omitted in the analysis: 99/182 in the azithromycin group (58 due to "no baseline pathogen", 15 due to "no end of therapy assessment", 15 due to "the presence of a resistant pathogen" (only main reasons mentioned)), 88/184 in the cephalexin group (55 due to "no baseline pathogen", 6 due to "no end of therapy assessment", 6 due to "the presence of a resistant pathogen" (main reasons mentioned)). > 20% no end of therapy assessment (not specified for impetigo only). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was a baseline comparison for sex, race, and primary diagnosis. There was no baseline imbalance. There were no compliance data. |
| Randomised? | Low risk | Quote: "Patients were randomly assigned in a double-blind fashion to one of the two treatment groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients were entered in the study based on..." Quote: "...were excluded by the protocol." |
| Methods | February 1999 to November 2000; Rotterdam, Netherlands; general practice; only impetigo | |
| Participants |
PNE | |
| Interventions | A: fusidic acid cream 2%, 3 td + povidone iodine shampoo, 2 td B: placebo cream, 3 td + povidone iodine shampoo, 2 td | |
| Outcomes | Outcomes of the trial 1) 7 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "An independent statistician provided a computer-generated list of random set numbers in permuted blocks of six. The hospital pharmacist packed the study medication in identical blank tubes with a number according to the randomisation list." |
| Allocation concealment (selection bias) | Low risk | See above - probably done: central allocation. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "Unblinding took place after the primary statistical analysis had been done." Quote: "....research nurse was unaware of treatment allocation." Quote: "...placebo cream did not differ." Quote: "Unblinding took place after the primary statistical analysis had been done." Comment: The outcome assessor, caregiver, and participant were probably all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 4/160 participants were omitted in the analysis (after 1 week): 2/78 in the fusidic acid cream group (both did not want to follow up), 2/82 in the placebo cream group (both did not want to follow up). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. There was more non-compliance in the placebo group. |
| Randomised? | Low risk | Quote: "Patients were randomised blockwise." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "General practitioners (GP's) in the Greater Rotterdam were asked to report patients aged 0-12 years with nonbullous impetigo presenting at their surgery." Quote: "Exclusion criteria were..." |
| Methods | April to December 2005; India, Mexico, Netherlands, Peru; hospital outpatients and general practice patients; only impetigo | |
| Participants |
| |
| Interventions | A: topical retapamulin 1% 2 td for 5 days B: topical placebo 2 td for 5 days | |
| Outcomes | Outcomes of the trial 1) Cured or improved after 7 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "Randomization was centre based and performed using an automated telephone system." |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "The packaging and labelling of study medication was identical for the active medication and its placebo counterpart. All efforts were made to make the study medication and placebo identical with respect to appearance and smell." The outcome assessor, caregiver, and participant were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 50/213 participants missing in total: 18/140 in the retapamulin group (1 did not receive intervention, 17 withdrawals (5 lack of efficacy, 3 disease progression, 2 decided to withdraw, 1 adverse event, 5 lost to follow up)), 33/73 in the placebo group (2 did not receive intervention, 31 withdrawals (18 lack of efficacy, 9 disease progression, 1 adverse event, 3 lost to follow up)). > 20% missing data. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "The mean total lesion area at baseline was larger in the retapamulin group compared with the placebo group." There was an imbalance for age. There were no compliance data. |
| Randomised? | Low risk | Quote: "We carried out a randomized..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Inclusion criteria were..." Quote: "...were excluded." |
| Methods | 1974; Columbus, Ohio, USA; outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | A: bacitracin ointment 500 units/g, 4 td + oral placebo 6 days B: erythromycin 250 mg 4 td + placebo cream, 6 days | |
| Outcomes | Outcomes of the trial 1) 6 days, cured/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Drug assignment was based on a random distribution table, without the knowledge of the authors." |
| Allocation concealment (selection bias) | Low risk | See above. |
| Blinding (performance bias and detection bias) patient | Low risk | See above. Also double dummy design. The outcome assessor, caregiver, and participant were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/30 participants were omitted in the analysis: 0/15 in the bacitracin group, 0/15 in the erythromycin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline comparison for the most important prognostic factors. There were no compliance data. |
| Randomised? | Low risk | Quote: "Drug assignment was based on a random distribution table, without the knowledge of the authors." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were enrolled in the study." Quote: "...were excluded." |
| Methods | 2002 to 2003; Japan; hospital outpatients; only impetigo | |
| Participants |
| |
| Interventions | A: topical tetracycline 3% 3 td + oral cefdinir 9 mg/kg/day for 7 days B: topical tetracycline 3% 3 td + oral minomycin 4 mg/kg/day for 7 days C: topical tetracycline 3% 3 td + oral fosfomycin 40 mg/kg/day for 7 days D: topical tetracycline 3% 3 td for 7 days | |
| Outcomes | Outcomes of the trial 1) Cured, improved after 7 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not reported. |
| Allocation concealment (selection bias) | Unclear risk | This was not reported. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...open-label." The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Only participants who were culture positive were analysed. The number of dropouts and withdrawals was not mentioned. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no compliance data. There was a baseline comparison for age and sex - no imbalance. |
| Randomised? | Low risk | Quote: "...randomized". |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were admitted to the study." Quote: "We excluded patients..." |
| Methods | February to May 1986 ; Scottsdale, Arizona, USA; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 to 9 days B: erythromycin 30 to 40/mg/kg/day in 3 to 4 doses, 7 to 9 days | |
| Outcomes | Outcomes of the trial 1) 8 to 12 days, very much improved/ improved/no change | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of four." |
| Allocation concealment (selection bias) | Low risk | Quote: "...investigator was blinded to the treatment the patient was to receive at the time of patient entry." |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "The investigator was blinded to the treatment the patient was to receive at the time of patient entry and was unblinded only in those cases where lesions persisted requiring additional culturing." Quote: "...open-label". This was not blinded for all participants. Also topical versus oral treatment. The outcome assessor and caregiver were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/60 participants were omitted in the analysis for clinical efficacy: 0/30 in the mupirocin group, 0/30 in the erythromycin group (2 participants in the erythromycin group discontinued therapy because of severe adverse experiences). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was a severe baseline imbalance, more fever in erythromycin group (12 versus 3), but they seem to have adjusted for this in the analysis. There were no compliance data. |
| Randomised? | Low risk | Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of four." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...were enrolled in the study." Quote: "Patients with...were excluded." |
| Methods | Time NR; San Juan, Puerto Rico; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 7 to 9 days C: erythromycin 30 to 50 mg/kg/day in 2 doses, 7 to 9 days | |
| Outcomes | Outcomes of the trial 1) 7 to 9 days, cured/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomized between the two treatment groups according to a computer-generated schedule having a block size of four." |
| Allocation concealment (selection bias) | Low risk | See above, and Quote: "The randomization was predetermined by the sponsor and the schedule for distribution of medications was entrusted to a team member whose assignment was to dispense medication." |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...were examined in a investigator-blinded study." Quote: "The randomization was predetermined by the sponsor and the schedule for distribution of medications was entrusted to a team member whose assignment was to dispense medication." Also, there was treatment with ointment versus capsules. The outcome assessor was blinded. The caregiver and the participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 22/75 participants were omitted in the analysis: 9 were missing in the mupirocin group (unclear why), 13 were missing in the in the erythromycin group (unclear why). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was an imbalance for sex: 17/28 versus 10/25 boys (assessable participants) = 61% vs 40%. There was no compliance data. |
| Randomised? | Low risk | Quote: "Patients were randomized between the two treatment groups according to a computer-generated schedule having a block size of four." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients 3 months of age and older of either sex who had no more than seven lesions of impetigo, cellulitis, abscesses, or furunculosis were admitted to the study." |
| Methods | Time NR; multicentre; Columbia Guatemala, Panama, South Africa; outpatients; range of skin infections (including impetigo 95/200) | |
| Participants |
PNE | |
| Interventions | A: azithromycin susp 10 mg/kg/day once daily, 3 days B: cefaclor susp 20 mg/kg/day in 3 doses, 10 days | |
| Outcomes | Outcomes of the trial 1) 10 to 14 days, cured + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Patients were randomly assigned in a 1:1 ratio to receive either..." It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "This open, comparative study..." Participants in both groups did not receive the same administrations of study drugs daily. Comment: The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 4/100 participants were omitted in the analysis (all attritions): 2/100 in the azithromycin group (due to loss of follow up), 2/100 in the cefaclor group (due to loss of follow up). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance for gender, age, weight, height, and ethnic origin. There were no compliance data. |
| Randomised? | Low risk | Quote: "Patients were randomly assigned in a 1:1 ratio to receive either..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Two hundred children...entered this multicentre..." Quote: "Patients were excluded from the study if...shown in Table I." |
| Methods | Time NR; Rio de Janeiro, Brasil; hospital outpatients; only impetigo | |
| Participants |
| |
| Interventions | 4 arms: A: sodium fusidate ointment 2%, 3 td, 10 days B: chloramphenicol ointment, 3 td, 10 days C: neomycin/bacitracin ointment, 3 td, 10 days D: erythromycin oral 50 mg/kg/day, in 4 dd, 10 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | High risk | Oral versus topical treatment. The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All 48 participants were analysed (see table 2). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no differences for sex. No other characteristics were reported. There were no compliance data. |
| Randomised? | Low risk | Quote: "Estes foram divididos aleatoriamente em quatro grupos de 12." [They were randomly divided in 4 groups of 12.] |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Quarenta e oito recem-nascidos entre tres e 14 dias de idade, portadores de impetigo estafilococico sem tratamento topica ou oral anterior, foram incluidos neste estudo." [40 and 8 neonates between 3 and 14 days old, who were carriers of impetigo stafylococcus without previous topical or oral treatment, had been enclosed in this study.] No exclusion criteria was specified. |
| Methods | Time NR; Plymouth/Bristol, UK; general practice; range of skin infections (including impetigo 89/354) | |
| Participants |
PNE | |
| Interventions | A: fusidic acid ointment 2%, 3 td, up to 7 days B: mupirocin ointment 2%, 3 td, up to 7 days | |
| Outcomes | Outcomes of the trial 1) 6 to 8 days, excellent/good | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "On entry, patients were allocated at random to receive one or other treatment, tubes of the ointment being provided in plain sealed numbered containers so that the investigator was unaware of the treatment given." Comment: This was probably done. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "On entry, patients were allocated at random to receive one or the other treatment, tubes of the ointment being provided in plain sealed numbered containers so that the investigator was unaware of the treatment given." Comment: The participants were probably blinded because the tubes were plain sealed. The outcome assessor was blinded. It is unclear whether the caregiver was blinded (it is unclear if the outcome assessor was also the caregiver). |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/354 participants were omitted in the analysis: 0/191 in the sodium fusidate group, 0/163 in the mupirocin group. Therapy was withdrawn in only 2 cases - 1 in each treatment group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was baseline comparison for sex, age, and severity. There were no compliance data. |
| Randomised? | Low risk | Quote: "On entry, patients were allocated at random to receive one or other treatment." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "The study involved 354 patients with acute superficial skin sepsis amenable to therapy with a topical antibiotic." Quote: "Patients who...were excluded." Quote: "...were also exclusion factors." |
| Methods | Time NR; Münster, Germany; outpatients; range of skin infections (including impetigo 66/80) | |
| Participants |
PE | |
| Interventions | A: sulconazole nitrate cream 1%, 2 td, 14 days B: miconazole nitrate cream 2%, 2 td, 14 days | |
| Outcomes | Outcomes of the trial 1) 7 days/14 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "When patients enrolled in the trial, they were allocated, according to a computer-generated randomization code, to receive either..." |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...double-blind, parallel comparative study". It is unclear if, and how, the outcome assessor, caregiver, and participant were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/80 participants were omitted in the analysis: 0/40 in the sulconazole group, 0/40 in the miconazole group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | The proportion of micro-organisms isolated at admission differs between groups (19 vs 6 for streptococcus, 53 vs 71 for S. aureus). There were no compliance data. |
| Randomised? | Low risk | Quote: "...according to a computer-generated randomization code..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients...were admitted to the trial." Quote: "...were excluded from the trial." |
| Methods | 2005; Canada, Costa Rica, France, Germany, India, The Netherlands, Peru, Poland, South Africa; outpatients; only impetigo | |
| Participants |
| |
| Interventions | A: topical retapamulin 1% 2 td for 5 days B: topical sodium fusidate 2% 3 td for 7 days | |
| Outcomes | Outcomes of the trial 1) Cure or improvement after 7 (retapamulin) or 9 days (sodium fusidate) | |
| Notes | Randomisation was 2:1. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | This was not reported. |
| Allocation concealment (selection bias) | Low risk | Quote: "...predetermined, center-based 2:1 schedule using the telephone-based interactive, central Registration and Medication Ordering System." |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...observer-blinded..." Quote: "...helped protect investigator blinding." Quote: "To maintain observer blinding..." Participants in both groups did not receive the same administrations of study drugs daily. Participants were not blinded, the outcome assessor was blinded, and the blinding of the caregiver is unclear |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 41/519 participants were missing data in both groups: 26/346 in the retapamulin group (26 prematurely discontinued, of which 8 had disease progression, 8 were lost to follow up, 1 had adverse events, 1 through lack of efficacy, 1 through protocol violation, 1 through potential conflicts of interest, 3 through 'other'), 15/172 in the sodium fusidate group (15 prematurely discontinued, of which 6 had disease progression, 1 was lost to follow up, 1 through subject decision [participant decision?], 3 had adverse events, 1 through lack of efficacy, 3 through 'other'), 1/519 were not included in the analysis. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. Compliance was comparable. |
| Randomised? | Low risk | Quote: "This was a randomised..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Subjects were included if..." Quote: "Subjects were excluded if..." |
| Methods | December 1988 to November 1990; Chiang Mai, Thailand; outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: penicillin V potassium 50 mg/kg/day in 4 doses, 7 days B: cloxacillin sodium 50 mg/kg/day in 4 doses, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure | |
| Notes | Bullous and non-bullous impetigo. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | This was not mentioned in the article: If the outcome assessor, caregiver, or participant was not blinded, he or she is likely to cause bias. All 3 were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 20/110 participants were omitted in the analysis: 45 were treated in the penicillin group and 45 were in the cloxacillin group (9 were unavailable for follow-up and 11 were negative to culture - not specified per group). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no baseline characteristics per group. There were no compliance data. |
| Randomised? | Low risk | Quote: "Participants were randomly assigned to receive either..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children... were invited to participate in the study." Quote: "Inclusion criteria included..." |
| Methods | April to November 1989; Baltimore, USA; outpatients and general practice; only impetigo | |
| Participants |
PNE | |
| Interventions | A: erythromycin ethynyl succinate 40 mg/kg/day in 4 doses, 10 days B: mupirocin ointment 2%, 3 td, 10 days | |
| Outcomes | Outcomes of the trial 1) 9 to 11 days, cure/improved/failure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "In any clinical trial that is not blinded..." Also, oral versus topical treatment. The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 10/93 participants were omitted in the analysis. The following were specified: 4/46 in the erythromycin group (4 did not return for follow-up), 6/47 in the mupirocin group (4 did not return for follow-up, 2 were excluded from completing the protocol, 1 had cellulites develop within a few hours after entry into the study, 1 whose primary provider added an oral antibiotic to the treatment regimen on day 3 of therapy even though the participant's condition was improving). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Low risk | The baseline characteristics were comparable. Compliance was good and comparable (table 6). |
| Randomised? | Low risk | Quote: "Children were randomly assigned to the two study groups." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "All children... were invited to participate." Quote: "Exclusion criteria included..." |
| Methods | Time NR; USA; outpatients; secondary impetigo (all eczema) | |
| Participants |
| |
| Interventions | A: topical mupirocin 2% 3 td + oral placebo for 10 days B: oral cephalexin 250 mg 4 td + topical placebo for 10 days | |
| Outcomes | Outcomes of the trial 1) Cured or improved after 12 to 13 days | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "...double-blind, double-dummy, parallel-group trial..." The outcome assessor, caregiver, and participant were all blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 33/159 (> 20%) participants did not complete the study (not specified per group). All 159 were in the ITT analysis. Participants whose outcome was indeterminable were considered failures. This may have introduced bias. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "Compliance was similar for both groups." Quote: "The mean SIRS scores were 20.5 for the mupirocin group and 19,1 for the cephalexin group (P = 0.09)." There was an imbalance for sex. |
| Randomised? | Low risk | Quote: "In this randomized..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Patients were eligible for entry into the trial if..." Quote: "Patients were excluded from the study if..." |
| Methods | Time NR; multicentre; Costa Rica, Guatemala, Panama, Venezuela; outpatients; range of skin infections (including impetigo 39/118) | |
| Participants |
PNE | |
| Interventions | 3 arms: A: azithromycin 10 mg/kg/day (max. 500), once daily, 3 days B: dicloxacillin12.5 to 25 mg/kg/day in 4 doses, 7 days (see notes) C: flucloxacillin 500 to 2000 mg/day in 4 doses (see notes) | |
| Outcomes | Outcomes of the trial 1) 7 to 10 days, cure/improved/failure | |
| Notes | Randomisation was between azithromycin and, either, dicloxacillin or flucloxacillin; the treatment groups dicloxacillin and flucloxacillin are combined in the results | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was provided. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was provided. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "An open, randomized..." The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Only 1 participant was missing (in which group was not specified). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline comparison (or compliance data) for the subgroup of impetigo participants. |
| Randomised? | Low risk | Quote: "An open, randomized..." Quote: "60 were randomized to receive..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Children...were eligible to enter this study." Quote: "Concurrent treatment with...was not permitted." Quote: "The principal exclusion criteria were..." Quote: "Persons were also excluded if..." |
| Methods | Time NR; Dominican Republic; hospital outpatients; only impetigo | |
| Participants |
PE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 10 to 12 days B: placebo/vehicle, 3 td, 10 to 12 days | |
| Outcomes | Outcomes of the trial 1) 7 to 12 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "The medication was numerically labelled; the protocol ensured double-blind comparisons." Bactroban ointment versus vehicle ointment. It is not clear whether the caregiver and outcome assessor are the same person. There was unclear blinding of the outcome assessor. The participant and the caregiver were probably blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: "Fifty patients completed the study." The number of participants that entered into the study was not specified. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline data. There were no compliance data. |
| Randomised? | Low risk | Bactroban ointment versus vehicle ointment - so, probably randomised but not clearly described. |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Patients with...entered in the study sequentially." No exclusion criteria was specified. |
| Methods | Summer 1972; Dallas, USA; outpatients; only impetigo | |
| Participants |
PNE | |
| Interventions | 5 arms: A: phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses + HS B: phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses C: HS + placebo D: placebo, 3 td E: bacitracin ointment, 2 td | |
| Outcomes | Outcomes of the trial 1) 5 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were assigned to one of five treatment groups by a random numbers list." Quote: "When more than one child from an household was entered in the study, all those children received the same treatment." Comment: This was probably done. |
| Allocation concealment (selection bias) | High risk | Quote: "Patients were assigned to one of five treatment groups by a random numbers list." Quote: "When more than one child from an household was entered in the study, all those children received the same treatment." Investigators knew that children in the same household got the same treatment. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "Phenoxymethyl penicillin suspension and placebo were coded as 'impecillin' and 'tigocillin'". Also, ointment versus suspension. The bacitracin was not placebo-controlled. Comment: The outcome assessor, caregiver, and participant were probably not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 24/102 participants were omitted in the analysis: 0/20 in group A (penicillin + hexachlorophene), 2/20 in group B (penicillin) (2 not streptococcal positive), 12/23 in group C (placebo) (6 not streptococcal positive, 6 failed to return for first follow-up), 4/17 in group D (placebo+hexachlorophene) (2 not streptococcal positive, 2 failed to return for first follow-up;), 6/22 in group E (bacitracin) (2 not streptococcal positive, 4 failed to return for first follow-up). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. Compliance was good for penicillin (based on urine test) but not reported for other therapy. |
| Randomised? | Low risk | Quote: "Patients were assigned to one of five treatment groups by a random numbers list." |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Children with... were excluded." Quote: "All patients were seen". |
| Methods | Time NR; UK; general practice (n = 20); only impetigo (only facial) | |
| Participants |
PNE | |
| Interventions | A: fusidic acid cream 3 td, 6 to 8 days B: mupirocin ointment 3 td, 6 to 8 days | |
| Outcomes | Outcomes of the trial 1) 8 days, cure + improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was provided. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was provided. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Investigators were not aware of the treatment given until the study was completed." Quote: "Treatment was allocated randomly in a double-blind manner, medication [was] dispensed in numbered, sealed containers." There was unclear blinding of the caregivers because it is unclear whether this is the same person as the outcome assessor. The participants were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 24/201 were omitted in the analysis: 93 were left in the fusidic acid group, 84 were left in the mupirocin group (not further specified). 177/201 were in the analysis. Of the 24 participants who were not analysed for efficacy, 20 returned for follow-up after more than 8 days, 2 defaulted, and 2 violated the study protocol. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. There were no compliance data. |
| Randomised? | Low risk | Quote: "Treatment was allocated randomly in a double-blind manner." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "A total of 201 patients requiring topical antibiotic treatment for facial impetigo were enrolled". Quote: "Exclusion criteria were..." |
| Methods | 1992 July to 1993 August; multicentre; US; outpatients; range of skin infections (including impetigo 225/394) | |
| Participants |
PE | |
| Interventions | A: cefdinir 7 mg/kg/day , 2 td, 10 days B: cephalexin 10 mg/kg/day, 4 td, 10 days | |
| Outcomes | Outcomes of the trial 1) 7 to 14 day, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was provided. |
| Allocation concealment (selection bias) | Unclear risk | It is unclear whether participants and investigators enrolling participants could foresee assignment. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...a multicenter, randomized, controlled, investigator-blind..." Also, participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor was blinded. The caregiver and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Quote: "...number of patients excluded for each reason comparable among groups." The proportion of participants not evaluable for reasons of non-compliance was unclear. Quote: "An intention-to-treat analysis was also performed. This analysis counted as failures all patients who had negative admission cultures or for whom follow-up information was not available." |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance (sex, age, race, infection type). There were no compliance data. |
| Randomised? | Low risk | Quote: "...a multicenter, randomized, controlled, investigator-blind..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Pediatric patients...were eligible for study entry." Quote: "Patients were prohibited from entering the study if..." |
| Methods | January to December 1992; multicentre; USA; outpatients, range of skin infections (including impetigo 62/952) | |
| Participants |
PE | |
| Interventions | A: cefdinir caps 300 mg, 2 td, 10 days B: cephalexin caps 500 mg, 4 td, 10 days | |
| Outcomes | Outcomes of the trial 1) 7 to 16 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was provided. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was provided. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "This was a double-mask, comparative, multicenter study." Quote: "Matched placebo capsules were dispensed appropriately to maintain study masking." It is not clear who was blinded (and how). It is unclear whether the outcome assessor and caregiver were blinded. The participants were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 952 randomised participants. Quote: "Of these, 178 cefdinir patients and 204 cephalexin patients were considered microbiologically assessable and were included in the efficacy analyses." > 20% not included in efficacy analysis because they were not assessed or the study drug was not taken as prescribed (table III). There was no intention-to-treat analysis. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Groups were similar at baseline (table II), though not specified for impetigo participants. There were no compliance data. |
| Randomised? | Low risk | Quote: "Patients were randomized 1:1 to receive..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Eligible patients were..." Quote: "Exclusion criteria included..." |
| Methods | Time NR; Mexico; outpatients; only impetigo | |
| Participants |
PE: not clear | |
| Interventions | A: rifamycin spray, 2 td, 7 days B: mupirocin ointment 2%, 2 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 1 week, cure/improved | |
| Notes | Both primary (n = 17) and secondary (n = 13) impetigo participants were studied. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...open trial". Also, spray versus ointment. The caregiver, outcome assessor, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 0/30 participants were omitted in the analysis: 0/15 in the rifamycin group, 0/15 in the mupirocin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. There were no compliance data. |
| Randomised? | Low risk | Quote: "...fueron asignados al azar." [...were assigned at random.] |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "En este estudio únicamente se incluyeron pacientes con lesiones localizades, con área no mayor de 10 cm² Los criterios de exclusión fueron niños con lesiones con un tiempo de evolución mayor de un mes." [In this study, patients were only included if the lesions were smaller than 10 cm². Exclusion criteria were children with lesions present longer than 1 month]. |
| Methods | Time NR; multicentre; Europe and South America; hospital-admitted and outpatients; range of skin infections (including impetigo 42/172) | |
| Participants |
PE | |
| Interventions | A: fleroxacin 400 mg, 1 td, 7 to 21 days B: amoxicillin/clavulanic acid tablets 500/125 mg, 3 td, 7 to 21 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...open-label". Participants in both groups did not receive the same administrations of study drugs daily. Also, investigators enrolling participants could possibly foresee assignment. The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Not only impetigo - it was not specified how many impetigo participants were randomised and included. 27 were analysed in the fleroxacin group, 15 were analysed in the amoxicillin/clavulanic group. Further data was not specified for impetigo participants. Not all participants were assessable for the efficacy analysis, but it was not stated how many. |
| Selective reporting (reporting bias) | Unclear risk | This was not unclear. |
| Other bias | Unclear risk | There was no baseline imbalance. There were no compliance data. |
| Randomised? | Low risk | Quote: "This study was designed as a prospective, randomized, open label..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Inpatients or outpatients of either sex were eligible for inclusion in the study if..." Quote: "Exclusion criteria were..." |
| Methods | March 1982 to January 1984; Denmark; general practice; only impetigo | |
| Participants |
PNE | |
| Interventions | 3 arms: A: fusidic acid cream 2% B: tetracycline/polymyxin B ointment C: neomycin/bacitracin ointment | |
| Outcomes | Outcomes of the trial 1) 1 week, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Undersøgelsen var således blindet for lægen, men ikke for patienten." [The study was blinded for the doctor, but not for the patient.] The outcome assessor and caregiver were blinded. Participants were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 6/134 participants were not included in the analysis: unknown group assignment, reasons were given. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was no baseline imbalance for severity. The used medication is in table 2. There were no compliance data. |
| Randomised? | Low risk | Quote: "...randomiseringsnummer." [...randomisation number.] |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "For at indgå i study skulle patienterne have klinisk verificeret impetigo"; "Udelukket var patienter med impetigeniserede eksemer, patienter med..." [Patients were eligible if they had clinical verified impetigo; Excluded were patients with impetiginised eczema and patients with...] |
| Methods | 1974; multicentre; USA; outpatients; only impetigo (secondary) | |
| Participants |
PNE | |
| Interventions | 3 arms: A: betamethasone valerate cream, 3 td B: gentamycin cream, 3 td C: betamethasone + gentamycin cream, 3 td | |
| Outcomes | Outcomes of the trial 1) 3 weeks, excellent result | |
| Notes | Secondary impetigo (impetiginised atopic dermatitis) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available |
| Blinding (performance bias and detection bias) patient | Low risk | Quote: "...precautions being observed to preserve the blinding of both patients and therapists." Also, participants in both groups received the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 4/83 participants were omitted in the analysis (not further specified). |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was a baseline comparison for severity and no imbalance. There were no compliance data. |
| Randomised? | Low risk | Quote: "Patients under the care of an individual investigator were randomly assigned." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "All patients enrolled were clinically judged to have moderate to severe impetiginized..." Quote: "In order to be accepted for the study..." Quote: " ...were excluded." |
| Methods | Time NR; London, UK; outpatients and general practice; range of skin infections (including impetigo 16/39) | |
| Participants |
PE: not clear | |
| Interventions | A: mupirocin ointment 2%, 2 td, 7 to 14 days B: chlortetracycline cream 3%, 2 td, 7 to 14 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Thirty-nine patients were entered in a randomized, observer-blind trail." Quote: "...but the medications were packaged identically and not opened in the presence of the physician." The outcome assessor and caregiver were blinded. Participants were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 3/39 participants were omitted in the analysis: 2/22 in the mupirocin group, 1/17 in the chlortetracycline group. These 3 were excluded from the analysis of results as they received systemic antibiotics for other infections while in the study. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There was a baseline imbalance for age (all infants were in the Bactroban group). This was not specified for impetigo. There were no compliance data. |
| Randomised? | Low risk | Quote: "Thirty-nine patients were entered in a randomized, observer-blind trail." |
| Were both inclusion and exclusion criteria specified? | High risk | Quote: "Patients with lesions suitable for treatment with a topical antibiotic were entered in the study." No exclusion criteria was specified. |
| Methods | Time NR; Monterrey, Mexico; outpatients; range of skin infections (including impetigo 15/60) | |
| Participants |
PNE | |
| Interventions | A: mupirocin ointment 2%, 3 td, 5 to 10 days B: ampicillin 50 mg, 4 td, 5 to 10 days | |
| Outcomes | Outcomes of the trial 1) 10 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | High risk | Quote: "...in an open trial." Thereby, the participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were not blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 10/60 participants were omitted in the analysis: 5/32 in the mupirocin group were lost to follow up, 5/28 in the ampicillin group were lost to follow up. These 10 participants were not analysed. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "Patient characteristics were similar in both treatment group in terms of sex, age, and weight." Table I shows no baseline imbalance for severity. There were no compliance data. |
| Randomised? | Low risk | Quote: "A randomized clinical trial..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "...outpatients with primary and secondary skin infections." Quote: "Patients were excluded from entry into the trial on the basis of..." |
| Methods | 1985 to 1987; UK; general practice; range of skin infections (including impetigo 155/390) | |
| Participants |
PNE | |
| Interventions | A: mupirocin ointment 2%, 2 td, 7 days B: fusidic acid ointment 2%, 3 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Low risk | Quote: "...and patients were randomised to receive treatment with either..." Quote: "For this purpose, a code was designed in blocks of six..." Quote: "The tubes were supplied in a sealed box labelled with the patient's number. Thereby the observer did not know which antibiotic a patient was receiving." Comment: This was probably done. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "Four plain tubes containing the preparations were supplied for each patient. These were labelled with instructions for use but the name of the antibiotic was omitted. Mupirocin was to be applied twice daily and sodium fusidate thrice daily." Quote: "The tubes were supplied in a sealed box labelled with the patient's number. Thereby the observer did not know which antibiotic a patient was receiving." The outcome assessor was blinded. The caregiver and participant were probably not blinded because they did not receive the same administrations of study drugs daily. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 23/413 participants were omitted in the analysis: 12/275 in the mupirocin group (8 failed to attend for assessment, 1 withdrew due to revised diagnosis, 3 were prescribed antibiotics for reasons other than lack of efficacy), 11/138 in the sodium fusidate group (3 failed to attend for assessment, 1 withdrew due to revised diagnosis, 2 were prescribed antibiotics for reasons other than lack of efficacy, 4 due to non-compliance, 1 due to inadequate data). < 20% dropouts, but reasons were not balanced between the groups. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | Quote: "There was a similar distribution of type and severity of infection between the two treatment groups". There were no compliance data. |
| Randomised? | Low risk | Quote: "...observer-blind randomised multi-centre clinical trial." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Any patient with primary or secondary skin infection, other than...was eligible for entry." Quote: "Patients were excluded if..." |
| ||
| Methods | Time NR; Quebec, Canada; outpatients; range of skin infections (including impetigo 10/50) | |
| Participants |
PE: not clear | |
| Interventions | A: mupirocin 2%, 3 td, 7 days B: polymyxin B-neomycin (Neosporin), 3 td, 7 days | |
| Outcomes | Outcomes of the trial 1) 7 days, cure/improved | |
| Notes | - | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Insufficient information was available. |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information was available. |
| Blinding (performance bias and detection bias) patient | Unclear risk | Quote: "...double-blind fashion." It was unclear how, and if, the outcome assessor, caregiver, and participant were blinded. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | There were 0/10 missing impetigo participants: 0/4 missing in the mupirocin group, 0/6 missing in the neosporin group. |
| Selective reporting (reporting bias) | Unclear risk | This was unclear. |
| Other bias | Unclear risk | There were no baseline characteristics. There were no compliance data. |
| Randomised? | Low risk | Quote: "...were randomly divided into..." |
| Were both inclusion and exclusion criteria specified? | Low risk | Quote: "Fifty patients who appeared at the dermatologic clinic with primary and secondary skin infections of...were randomly divided..." Quote: "...were excluded from the trial." |
| Study | Reason for exclusion |
|---|---|
| Alavena 1987 | Randomisation was inadequate. |
| Anonymous 1998 | Results were not separately described for impetigo participants: no randomisation. |
| Arata 1983 | Randomisation was inadequate (serial allocation). |
| Arata 1994 | The results were not separately described for impetigo participants. |
| Arosemena 1977 | The results were not separately described for impetigo participants: only 6/343 participants had impetigo. |
| Azimi 1999 | The results were not separately described for impetigo participants. |
| Baldwin 1981 | The same drug was compared. |
| Ballantyne 1982 | The results were not separately described for impetigo participants: no randomisation. |
| Bastin 1982 | The results were not separately described for impetigo participants. |
| Bernard 1997 | The results were not separately described for impetigo participants (requested, but no reply). |
| Bin Jaafar 1987 | No participants had impetigo ( "pyoderma"). |
| Burnett 1963 | There was no randomisation. |
| Cassels-Brown 1981 | The design was unacceptable (no RCT). |
| Colin 1988 | The results were not separately described for impetigo participants. |
| Cordero 1976 | There was only 1 impetigo participant. |
| De Waard 1967 | There was no randomisation: 2 arms with the same active drug (though different mode of administration). |
| Dillon 1970 | There was no randomisation. |
| Dillon 1979a | The results were not separately described for impetigo participants. |
| Drehobl 1997 | The results were not separately described for impetigo participants (requested, but no reply). |
| el Mofty 1990 | The results were not separately described for impetigo participants. |
| Esterly 1970 | There was no randomisation. |
| Faingezicht 1992 | The results were not separately described for impetigo participants. |
| Fedorovskaia 1989 | Randomisation was inadequate. |
| Fleisher 1983 | The results were not separately described for impetigo participants. |
| Forbes 1952 | The same drug was compared. |
| Free 2006 | No participants had impetigo (communication: Nicole E. Scangarella). |
| Gentry 1985 | The results were not separately described for impetigo participants. |
| Gibbs 1987 | All impetigo participants received the same treatment. |
| Golcman 1997 | The results were not separately described for impetigo participants (requested, but no reply). |
| Goldfarb 1987 | The results were not separately described for impetigo participants. |
| Gooch 1991 | The results were not separately described for impetigo participants. |
| Hanfling 1992 | The results were not separately described for impetigo participants. |
| Harding 1970 | There was 1 drug (flucloxacillin) in 2 doses: the results for impetigo participants were not separately described. |
| Heskel 1992 | The results were not separately described for impetigo participants. |
| Jacobs 1992 | The results were not separately described for impetigo participants. |
| Jennings 1999 | There was only 1 impetigo participant. |
| Jennings 2003 | The results were not separately described for impetigo participants (requested, but no reply). |
| Keeny 1979 | The results were not separately described for impetigo participants. |
| Kotrajaras 1973 | The results were not separately described for impetigo participants. |
| Kumakiri 1988 | There was only 1 impetigo participant. |
| Kumar 1988 | No participants had impetigo: 2 forms of the same drug. |
| Lassus 1990 | The results were not separately described for impetigo participants. |
| Lentino 1984 | There was only 1 impetigo participant. |
| Levenstein 1982 | The results were not separately described for impetigo participants. |
| Lewis-Jones 1985 | The results were not separately described for impetigo participants. |
| Linder 1978 | The results were not separately described for impetigo participants. |
| Linder 1993 | The results were not separately described for impetigo participants. |
| Lipets 1987 | No comparison was made. |
| Liu 1986 | No participants had impetigo (impetigo herpetiformis). |
| MacKenna 1945 | Randomisation (serial allocation) was inadequate. |
| Macotela-Ruiz 1988 | The results were not separately described for impetigo participants (requested, but no reply). |
| Mallory 1991 | The results were not separately described for impetigo participants. |
| Manaktala 2009 | The results were not separately described for impetigo participants. |
| McCarty 1992 | The results were not separately described for impetigo participants. |
| McMillan 1969 | The results were not separately described for impetigo participants. |
| Milidiú d Silva 1985 | The results were not separately described for impetigo participants. |
| Nakayama 1983 | The results were not separately described for impetigo participants, and it was not an RCT. |
| Neldner 1991 | The results were not separately described for impetigo participants. |
| Nichols 1997 | The results were not separately described for impetigo participants. |
| Nicolle 1990 | The results were not separately described for impetigo participants. |
| Nolting 1992 | No participants had impetigo (pyoderma). |
| Orecchio 1986 | The results were not separately described for impetigo participants. |
| Pakrooh 1978 | No participants had impetigo. |
| Palazzini 1993 | The results were not separately described for impetigo participants. |
| Parish 1984 | The results were not separately described for impetigo participants. |
| Parish 1991 | The results were not separately described for impetigo participants. |
| Parish 1992 | The results were not separately described for impetigo participants. |
| Parish 1997 | The results were not separately described for impetigo participants. |
| Parish 2000 | The results were not separately described for impetigo participants (requested, but no data available). |
| Parish 2006 | No participants had impetigo (communication: Nicole E. Scangarella). |
| Park 1993 | There was no randomisation (personal communication: Seungsoo Sheen). |
| Pien 1983 | The results were not separately described for impetigo participants. |
| Powers 1991 | There were no separate results for clinical cure. |
| Powers 1993 | There were only 2 impetigo participants. |
| Pusponegoro 1990 | There was only 1 impetigo participant, |
| Risser 1985 | The results were not separately described for impetigo participants. |
| Saenz 1985 | The results were not separately described for impetigo participants. |
| Salzberg 1972 | There was only 1 impetigo participant. |
| Schupbach 1992 | The results were not separately described for impetigo participants. |
| Schwartz 1996 | There was only 1 impetigo participant. |
| Smith 1985 | The results were not separately described for impetigo participants. |
| Smith 1993 | There was only 1 impetigo participant. |
| Sobye 1966 | The results were not separately described for impetigo participants. |
| Stevens 1993 | There were 5 participants with "pyoderma". |
| Tack 1991 | The results were not separately described for impetigo participants, and the same drug was compared. |
| Török 2004 | The same drug was compared. |
| Urbach 1966 | No randomisation was described. |
| Van der Auwera 1985 | No participants had impetigo. |
| Villiger 1986 | The results were not separately described for impetigo participants. |
| Wachs 1992 | The results were not separately described for impetigo participants. |
| Wible 2003 | The results were not separately described for impetigo participants (requested, but no reply). |
| Wolbling 1987 | 2 doses of 1 drug were compared. |
| Wong 1989 | The results were not separately described for impetigo participants. |
| Yura 1988 | The results were not separately described for impetigo participants. |
| Methods | This is an RCT. |
| Participants |
|
| Interventions | Intervention A: clindamycin Control intervention B: cephalexin |
| Outcomes | Primary outcomes of the trial 1) Improvement Secondary outcomes of the trial 1) Complete resolution |
| Notes | This is a result of the CSG searches that were run in August 2011. It is not known how many participants were impetigo patients. |
| Methods | This is an RCT. |
| Participants |
|
| Interventions | Intervention A: cloxacillin Control intervention B: pristinamycin |
| Outcomes | Outcomes of the trial 1) Cure |
| Notes | This will be included when data on impetigo participants is provided. |
| Methods | Please see the 'notes' cell below. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | This is a result of the CSG searches that were run in August 2011. We were unable to obtain a copy of this trial. |
| Methods | This is possibly an RCT. |
| Participants |
|
| Interventions | Intervention A: neem, haldi, sajina, and garlic oil (Nutriderm oil) Control intervention B: gentian violet |
| Outcomes | Primary outcomes of the trial 1) Cure Secondary outcomes of the trial 1) Side-effects |
| Notes | - |
| Methods | Please see the 'notes' cell below. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | This paper was published in Spanish, and we were unable to obtain a copy. |
| Methods | This is possibly an RCT. |
| Participants |
|
| Interventions | Intervention A: injection benzathine penicillin Control intervention B: oral sulphamoxole |
| Outcomes | Outcomes of the trial 1) Cure after 1 and 2 weeks |
| Notes | There did not appear to be separate results for impetigo. |
| Methods | This is possibly an RCT. |
| Participants |
|
| Interventions | Intervention A: 125 mg amoxicilin plus 30 mg clavulanate per 5 ml of suspension, equivalent to 20 mg amoxicillin/kg/day in 3 divided doses Control interventions B: amoxicillin 20 mg/kg/day in 3 divided doses C: erythromycin 30 mg/kg/day in 4 divided doses D: co-trimoxazole (8 mg trimethoprim + 40 mg sulfamethoxazole/kg/day) in 2 divided dosis |
| Outcomes | Primary outcomes of the trial 1) Presence of S. aureus Secondary outcomes of the trial 1) Cure 2) Adverse events |
| Notes | It was not clear if pyoderma equated to impetigo. |
| Methods | This is an RCT. |
| Participants |
|
| Interventions | Intervention A: 1.2% triclocarban-containing soap Control intervention B: an identically appearing placebo |
| Outcomes | Outcomes of the trial 1) Impetigo incidence |
| Notes | This is a result of the CSG searches that were run in August 2011. |
| Methods | This is possibly an RCT. |
| Participants |
|
| Interventions | Intervention A: sunflower oil Control intervention B: mupirocin |
| Outcomes | Primary outcomes of the trial 1) Clinical cure after possibly 6 days |
| Notes | This paper was written in Spanish. |
| Methods | This is an RCT. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | This is a result of the CSG searches that were run in August 2011. We were unable to obtain a copy of this trial. |
| Methods | This is an RCT. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | This is a result of the CSG searches that were run in August 2011. We were unable to obtain a copy of this trial. |
| Methods | This is possibly an RCT. |
| Participants |
|
| Interventions | Intervention A: tea lotion B: tea ointment C: soframycin D: oral cephalexin |
| Outcomes | Primary outcomes of the trial 1) Cure after 7 to 10 days |
| Notes | - |
| Methods | This is an RCT. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | This is a result of the CSG searches that were run in August 2011. We were unable to obtain a copy of this trial. |
| Methods | This is a pilot study. |
| Participants |
|
| Interventions | Intervention A: oral cotrimoxazole B: intramuscular benzathine penicillin |
| Outcomes | Primary outcomes of the trial 1) Resolution of skin sores |
| Notes | Australian Trial Register: Is cotrimoxazole safe and efficacious for treatment of skin sores in Aboriginal children: a pilot study Published in the Journal of Pediatrics and Child Health 2010;46:131-133 |
| Methods | This is possibly an RCT. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | We were unable to obtain a copy of this trial. |
| Methods | This is possibly an RCT. |
| Participants | Please see the 'notes' cell below. |
| Interventions | Please see the 'notes' cell below. |
| Outcomes | Please see the 'notes' cell below. |
| Notes | We were unable to obtain a copy of this trial. |
| Trial name or title | An open label randomised controlled trial to determine if 5 days of once-daily oral trimethoprim-sulfamethoxazole or three days of twice-daily oral trimethoprim-sulfamethoxazole will lead to non-inferior cure rates of impetigo compared to a single dose of intramuscular benzathine penicillin G (the current gold standard treatment) in children living in remote Aboriginal communities between the age of 12 weeks to less than 13 years |
| Methods | See title. |
| Participants | Inclusion criteria of the trial 1. Age 12 weeks to less than 13 years at the time written consent is obtained |
| Interventions | Group 1: single dose intramuscular benzathine penicillin G - weight band-based dosing up to 900 mg (> 3 and < 6 kg = 225 mg; > 6 and < 10 kg = 337.5 mg; > 10 and < 15 kg = 450 mg; > 15 and < 20 kg = 675 mg; > 20 kg = 900 mg) Group 2: trimethoprim-sulfamethoxazole oral suspension 8 + 40 mg/kg (max 320 + 1600 mg) daily for 5 days Group 3: trimethoprim-sulfamethoxazole oral suspension 4 + 20 mg/kg (max 160 + 800 mg) twice daily for 3 days |
| Outcomes | Primary outcomes of the trial 1) The proportion of children successfully treated on day 7 after the commencement of treatment within each of the respective groups. Successfully treated is defined as a child with impetigo which has been clinically classified as sore either healed or improved by a person blinded to the allocated randomisation Secondary outcomes of the trial 1) The proportion of children within each of the respective groups who are defined as being successfully treated on day 2 2) Prevalence of Staphylococcus aureus (methicillin susceptible and methicillin resistant) and Group A Streptococci per child at day 0, day 2, and day 7 within each treatment group as determined from impetigo swabs collected at the respective time points 3) Effect of each treatment on the bacterial resolution of sores at days 2 and 7 as determined by impetigo swabs collected at the respective time points 4) Prevalence of nasal carriage of Staphylococcus aureus at baseline and day 7 (including a comparison of the prevalence of methicillin-resistant S. aureus at baseline and day 7) 5) Evidence of allergy or other reaction to the medication within 7 days of first administration as determined by clinical observation and questioning of caregivers |
| Starting date | 1st December 2009 |
| Contact information | Ross Andrews (ross.andrews@menzies.edu.au) Menzies School of Health Research PO Box 41096 Casuarina, 0811, NT, Australia |
| Notes | Australian New Zealand Clinical Trial Registry: ACTRN12609000858291 |
| Trial name or title | An Open Labelled, Double Arm, Randomized, Multicentric, Prospective And Comparative, Phase-III Trial To Evaluate The Safety And Efficacy Of Fixed Dose Combination Of Ceftriaxone And Vancomycin Injection Vs. Vancomycin Injection In Subjects With Various Bacterial Infections |
| Methods | See above. |
| Participants | Inclusion criteria of the trial
|
| Interventions | See above. |
| Outcomes | Primary outcomes of the trial 1) Compare the efficacy of a 3.0 g FDC of ceftriaxone and vancomycin injection vs 1.0 g vancomycin injection in subjects with mild to severe bacterial infections Secondary outcomes of the trial 1) Evaluate the safety of the test and comparative product |
| Starting date | 8th April 2008 |
| Contact information | kundan.k@nexuscro.com |
| Notes | It is unclear whether impetigo participants will be included. |
| Trial name or title | Sisomicin Cream Vs Nadifloxacin Cream in Primary Pyodermas |
| Methods | This was to be a randomised, active-control trial. End point classification - safety/efficacy study Intervention model - parallel assignment Masking - open-label Primary purpose - treatment |
| Participants | Inclusion criteria of the trial
|
| Interventions | See title. |
| Outcomes | None were stated. |
| Starting date | May 2007 |
| Contact information | Ragunandan Torsekar, MD, FCPS (Principal Investigator) Rajiv Gandhi Medical College |
| Notes | The current status of the trial is withdrawn (NCT00202891). |
| Trial name or title | Efficacy, Safety, and Tolerability of TD1414 2% Cream in Impetigo and Secondarily Infected Traumatic Lesions (SITL) |
| Methods | Quote: "This is an international, multicentre, prospective 3-arm parallel-group, phase II proof of concept study comparing the efficacy and safety of 2 dosage regimens (BID 7 days and TID 7 days) of TD1414 2% cream and 1 dosage regimen (BID 7 days) of Bactroban® (mupirocin) 2% cream in adults and children down to 2 years of age with impetigo or SITL. Furthermore, an evaluation of the pharmacokinetics of TD1414 2% cream TID for 7 days will be performed. A total of 664 patients will be enrolled in a stepwise manner according to age groups starting with the oldest age group." |
| Participants | See above. |
| Interventions | See above. |
| Outcomes | Primary outcomes of the trial 1) Clinical cure at end of treatment according to investigator's assessment Secondary outcomes of the trial 1) Clinical cure at follow-up according to investigator's assessment 2) Clinical cure at end of treatment and follow-up according to investigator's assessment 3) Bacteriological cure at end of treatment and follow-up |
| Starting date | February 2008 |
| Contact information | Almena L Free, MD (Principal Investigator) Anniston Medical Clinic Anniston, Alabama, United States 36207 |
| Notes | www.clinicaltrials.gov |
| Trial name or title | A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Oral Linezolid in the Treatment of Secondarily-Infected Traumatic Lesions and Impetigo Due to Methicillin-Resistant Staphylococcus Aureus |
| Methods | See above. |
| Participants | See above. |
| Interventions | See above. |
| Outcomes | Primary outcomes of the trial 1) Number of participants achieving clinical response at follow-up who had methicillin-resistant Staphylococcus aureus (MRSA) as a baseline pathogen Secondary outcomes of the trial 1) Number of participants achieving microbiological response at follow-up who had MRSA as a baseline pathogen 2) Number of participants with clinical response at follow-up 3) Number of participants who achieved microbiological response at follow-up who had a baseline pathogen 4) Number of participants with the indicated clinical outcome at the end of therapy who had MRSA as a baseline pathogen 5) Number of participants with the indicated microbiological outcome at the end of therapy who had MRSA as a baseline pathogen 6) Number of participants with the indicated clinical outcome at the end of therapy 7) Number of baseline pathogens with the indicated microbiological outcome at the end of therapy 8) Number of participants with therapeutic response at follow-up 9) Mean scores on the skin infection rating scale at visits 1, 2, 3, 4, and 5 10) Mean wound size at visits 1, 2, 3, 4, and 5 |
| Starting date | April 2009 |
| Contact information | Study Director GSK Clinical Trials GlaxoSmithKline |
| Notes | - |
| Trial name or title | A Phase IV Study Comparing Clinical and Bacteriological Efficacy of Fucidin® Cream With Fucidin® Cream Vehicle in the Treatment of Impetigo in Paediatric Patients |
| Methods | This is a randomised, placebo-controlled trial. End point classification - safety/efficacy Study Intervention model: parallel assignment Masking - double-blind (subject, investigator) Primary purpose - treatment |
| Participants | Inclusion criteria of the trial
|
| Interventions | A: Fucidin® cream versus Fucidin® cream vehicle |
| Outcomes | Primary outcomes of the trial 1) The proportion of participants with clinical success (marked improvement or completely cleared) and bacteriological success (eradication) at end of treatment (EOT) Secondary outcomes of the trial |
| Starting date | May 2004 |
| Contact information | Inga Odenholt (Principal Investigator) Malmö University Hospital |
| Notes | Infomation was obtained from clinicaltrials.gov. Information was requested in August 2010. |
| Trial name or title | A Randomized, Parallel-group, Double Blind, Clinical Trial, to Asses the Safety and Efficacy of Topically Applied FXFM244 Antibiotic Foam in the Treatment of Impetigo |
| Methods | This is a randomised, parallel-group, double (Investigator, participant)-blind, comparative dose range-finding clinical trial. |
| Participants | Inclusion criteria of the trial
|
| Interventions | The study will involve 2 treatment groups. A: Eligible participants will be randomised to receive either FXFM244 - 1% or FXFM244 - 4% in a blinded fashion. Participants will be treated twice daily for 7 days. Following the screening period and baseline visit, study subjects will return at days 3, 7 and 14. At each visit, participants will be evaluated via lesion count, global assessment tolerability, and safety. |
| Outcomes | Primary outcomes of the trial 1) Decrease in lesion count 7 days Secondary outcomes of the trial 1) The severity of the overall impetigo condition will be measured at baseline and at all follow-up visits. The severity will be assessed and graded based on the scales for Investigator's Global Assessment and bacteriological testing (days 3, 7, and 14) |
| Starting date | August 2010 |
| Contact information | Foamix Ltd. Lev Yasmin Clinic |
| Notes | This study is probably not eligible for inclusion as 2 dosages of the same drug are used. |
