Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults

  • Review
  • Intervention

Authors


Abstract

Background

Dental pain can have a considerable detrimental effect on an individual's quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with symptomatic apical periodontitis or an acute apical abscess should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists continue to prescribe antibiotics for these conditions. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies both within the individual and within the community as a whole.

Objectives

To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis or acute apical abscess in adults.

Search methods

We searched the following electronic databases: Cochrane Oral Health Group's Trials Register (to 1 October 2013); Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 9); MEDLINE via OVID (1946 to 1 October 2013); EMBASE via OVID (1980 to 1 October 2013) and CINAHL via EBSCO (1980 to 1 October 2013). We searched the World Health Organization (WHO) International Trials Registry Platform and the US National Institutes of Health Trials Registry (ClinicalTrials.gov) on 1 October 2013 to identify ongoing trials. We searched for grey literature using OpenGrey (to 1 October 2013) and ZETOC Conference Proceedings (1993 to 1 October 2013). We placed no restrictions on the language or date of publication when searching the electronic databases.

Selection criteria

Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics.

Data collection and analysis

Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data and, where results were meta-analysed, we used a fixed-effect model as there were fewer than four studies. We contacted study authors to obtain missing information.

Main results

We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo given in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth (no signs of spreading infection or systemic involvement (fever, malaise)). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.

The primary outcome variables presented were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects as reported in one study were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). No studies reporting quality of life measurements were suitable for inclusion.

Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess.
Two studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth. Participants in one study all underwent a total pulpectomy of the affected tooth while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality.

Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess.
We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.

Authors' conclusions

There is very low quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.

Résumé scientifique

Les antibiotiques systémiques dans la parodontite apicale symptomatique et l'abcès apical aigu chez l'adulte

Contexte

La douleur dentaire peut avoir un effet néfaste considérable sur la qualité de vie d'une personne. La parodontite apicale symptomatique et l’abcès apical aigu sont des causes courantes de douleurs dentaires et résultent d'une pulpe dentaire inflammée ou nécrotique ou d’une infection du système de canal radiculaire dévitalisé. Les directives cliniques recommandent que le traitement de première intention pour les dents avec une parodontite apicale symptomatique ou un abcès apical aigu soit le retrait de la source d'inflammation ou d'infection par des mesures opératoires locales, et les antibiotiques systémiques sont actuellement recommandés uniquement dans les situations où il existe des preuves d'une propagation de l'infection (cellulite, implication des ganglions lymphatiques, œdème diffus) ou d'implication systémique (fièvre, malaise). Malgré cela, il existe des données indiquant que les dentistes continuent à prescrire des antibiotiques pour ces pathologies. Il est à craindre que cela puisse contribuer au développement de colonies bactériennes résistantes aux antibiotiques, chez l'individu et au sein de la communauté dans son ensemble.

Objectifs

Évaluer les effets des antibiotiques systémiques fournis avec ou sans intervention chirurgicale (telles qu'une extraction, l'incision et le drainage d'un œdème ou un traitement endodontique), avec ou sans analgésique, dans la parodontite apicale symptomatique ou l’abcès apical aigu chez l'adulte.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans les bases de données électroniques suivantes : le registre d'essais cliniques du groupe Cochrane sur la santé bucco-dentaire (jusqu'au 1er octobre 2013) ; le registre Cochrane des essais contrôlés (Bibliothèque Cochrane 2013, numéro 9) ; MEDLINE via OVID (de 1946 jusqu'au 1er octobre 2013) ; EMBASE via OVID (de 1980 au 1er octobre 2013) et CINAHL via EBSCO (de 1980 au 1er octobre 2013). Nous avons effectué des recherches dans le système d'enregistrement international des essais cliniques de l'Organisation mondiale de la Santé (OMS) et le registre d'essais des US National Institutes of Health (NIH) (ClinicalTrials.gov) le 1er octobre 2013 pour identifier les essais en cours. Nous avons exploré la littérature grise en utilisant OpenGrey (jusqu'au 1er octobre 2013) et ZETOC ConferenceProceedings (de 1993 jusqu'au 1er octobre 2013). Nous n’avons placé aucune restriction sur la langue ou la date de publication lors des recherches dans les bases de données électroniques.

Critères de sélection

Essais contrôlés randomisés d'antibiotiques systémiques chez les adultes ayant reçu un diagnostic clinique de parodontite apicale symptomatique ou d’abcès apical aigu, avec ou sans intervention chirurgicale (c’est-à-dire extraction, incision et drainage ou traitement endodontique) et avec ou sans analgésiques.

Recueil et analyse des données

Deux auteurs de la revue ont passé au crible les résultats des recherches par rapport aux critères d'inclusion, extrait les données et évalué le risque de biais de manière indépendante et en double. Nous avons calculé les différences moyennes (DM) (ou la différence moyenne standardisée (DMS) lorsque différentes échelles étaient rapportés) et des intervalles de confiance (IC) à 95 % pour les données continues et, lorsque les résultats étaient soumis à une méta-analyse, nous avons utilisé un modèle à effets fixes, car il y avait moins de quatre études. Nous avons contacté les auteurs des études afin d'obtenir des informations manquantes.

Résultats principaux

Nous avons inclus deux essais dans cette revue, avec 62 participants inclus dans les analyses. Les deux essais ont été menés dans des écoles dentaires universitaires aux États-Unis et ont comparé les effets de la pénicilline V potassium (pénicilline VK) orale versus un placebo apparié, administrés conjointement à une intervention chirurgicale (pulpectomie totale ou partielle) et des analgésiques pour les adultes atteints d'abcès apical aigu ou de nécrose symptomatique de la dent (aucun signe de propagation de l'infection ou d'implication systémique (fièvre, malaises)). Nous avons évalué une étude comme présentant un risque élevé de biais et l'autre étude comme présentant un risque de biais incertain.

Les critères de jugement principaux présentés étaient la douleur et l'œdème rapportés par le participant (un essai rendait également compte de la douleur à la percussion rapportée par le participant). Une étude a rapporté le type et le nombre d'analgésiques pris par les participants. Une étude a enregistré l'incidence des poussées endodontiques postopératoires (les personnes qui revenaient avec des symptômes nécessitant un traitement supplémentaire). Les effets indésirables rapportés dans une étude étaient la diarrhée (un participant du groupe de placebo) ainsi que la fatigue et une énergie réduite après l'opération (un participant du groupe des antibiotiques). Aucune étude rapportant des mesures de la qualité de vie n’a satisfait aux critères d'inclusion.

Objectif 1 : antibiotiques systémiques versus placebo avec intervention chirurgicale et analgésiques pour la parodontite apicale symptomatique ou l'abcès apical aigu.
Deux études ont fourni des données pour la comparaison entre les antibiotiques systémiques (pénicilline VK) et un placebo apparié chez des adultes souffrant d’un abcès apical aigu ou d’une dent nécrosée symptomatique. Dans une étude, les participants ont tous subi un pulpectomie totale de la dent atteinte tandis que dans l'autre étude, les participants étaient traités par pulpectomie partielle ou totale. Les participants dans les deux essais avaient reçu des analgésiques par voie orale. Il n'y avait aucune différence statistiquement significative dans les mesures de la douleur ou de l'œdème rapportées par les participants à aucun des points temporels évalués dans la revue. La DM pour la douleur (sur une échelle ordinale numérique courte allant de 0 à 3) était de -0,03 (IC à 95 % de -0,53 à 0,47) au bout de 24 heures ; de 0,32 (IC à 95 % de -0,22 à 0,86) au bout de 48 heures et de 0,08 (IC à 95 % de -0,38 à 0,54) au bout de 72 heures. La DMS pour l'œdème était de 0,27 (IC à 95 % de -0,23 à 0,78) au bout de 24 heures ; de 0,04 (IC à 95 % de -0,47 à 0,55) au bout de 48 heures et de 0,02 (IC à 95 % de -0,49 à 0,52) au bout de 72 heures. Le corpus de preuves a été évalué comme étant de très faible qualité.

Objectif 2 : antibiotiques systémiques sans intervention chirurgicale pour les adultes souffrant de parodontite apicale symptomatique ou d’abcès apical aigu.
Nous n'avons trouvé aucune étude comparant l’effet des antibiotiques systémiques avec un placebo apparié administré sans intervention chirurgicale pour une parodontite apicale symptomatique ou un abcès apical aigu chez l'adulte.

Conclusions des auteurs

Il existe des preuves de très faible qualité qui sont insuffisantes pour déterminer les effets des antibiotiques systémiques sur les adultes atteints de parodontite apicale symptomatique ou d’abcès apical aigu.

Plain language summary

The effects of antibiotics on toothache caused by inflammation or infection at the root of the tooth in adults

This review, carried out by authors of the Cochrane Oral Health Group, has been produced to assess the effects of antibiotics on pain and swelling in two conditions commonly responsible for causing dental pain when given with or without dental treatment (such as extraction, drainage of a swelling or root canal treatment).

Background

Dental pain is a common problem and can arise when the nerve within a tooth dies due to progressing decay or severe trauma. The tissue around the end of the root then becomes inflamed and this can lead to acute pain, which gets worse on biting. Without treatment, bacteria can infect the dead tooth and cause a dental abscess, which can lead to swelling and spreading infection that may be life threatening.

The recommended treatment of this form of toothache is the removal the dead nerve and associated bacteria. This is usually done by dental extraction or root canal treatment. Antibiotics should only be prescribed when there is severe infection that has spread from the tooth. However, some dentists still routinely prescribe oral antibiotics to people with acute dental conditions that have no signs of spreading infection.

Minimising inappropriate antibiotic prescribing is plays a key role in limiting the development of antibiotic-resistant bacteria. Since dentists prescribe approximately 8% to 10% of all primary care antibiotics in developed countries, dental prescribing may contribute to antibiotic resistance. Therefore, it is important that antibiotics should only be used when they are clinically beneficial for the person.

Study characteristics

The evidence on which this review is based was up to date as of 1 October 2013. We searched scientific databases and found two trials, with a 62 participants included in the analysis. Both trials were conducted at university dental schools in the USA and evaluated the use of oral antibiotics in the reduction of pain and swelling reported by adults after having the first stage of root canal treatment under local anaesthetic. The antibiotic used in both trials was penicillin VK and all participants also received painkillers.

Key results

The two studies included in the review reported that there were no clear differences in the pain or swelling reported by participants who received oral antibiotics compared with a placebo (a dummy treatment) when provided in conjunction with the first stage of root canal treatment and painkillers, but the studies were small and we could not exclude potentially important differences between groups. Neither study examined the effect of antibiotics delivered by themselves, without dental treatment.

One trial reported side effects among participants: one person who received the placebo medication had diarrhoea and one person who received antibiotics experienced tiredness and reduced energy after their operation.

Quality of evidence

We judged the quality of evidence to be very low. There is currently insufficient evidence to be able to determine the effects of antibiotics in these conditions.

Résumé simplifié

Les effets des antibiotiques sur des douleurs dentaires provoquées par une inflammation ou une infection de la racine de la dent chez l'adulte

Cette revue, menée par des auteurs du groupe Cochrane sur la santé bucco-dentaire, a été produite pour évaluer les effets des antibiotiques sur la douleur et le gonflement dans deux pathologies couramment responsables de douleurs dentaires lorsqu’ils sont administrés avec ou sans traitement dentaire (tels qu'une extraction, le drainage d'un gonflement ou le traitement du canal radiculaire).

Contexte

La douleur dentaire est un problème courant et peut survenir lorsque le nerf à l'intérieur de la dent meurt en raison d'une carie évolutive ou d’un traumatisme grave. Les tissus autour de l'extrémité de la racine deviennent alors inflammés et cela peut provoquer une douleur aiguë, qui s’aggrave lors de la mastication. Sans traitement, des bactéries peuvent infecter la dent morte et entraîner un abcès dentaire, ce qui peut conduire à un gonflement et à la propagation de l'infection, qui peut être mortelle.

Le traitement recommandé de cette forme de douleurs dentaires est l'ablation du nerf mort et des bactéries associées. Ceci est généralement réalisé par l'extraction dentaire ou un traitement du canal radiculaire. Les antibiotiques ne devraient être prescrits que dans le cas d’une infection grave qui se serait propagée à partir de la dent. Cependant, certains dentistes prescrivent encore systématiquement des antibiotiques oraux aux personnes atteintes de pathologies dentaires aiguës qui ne présentent aucun signe de propagation de l'infection.

La minimisation de la prescription inappropriée d'antibiotiques joue un rôle essentiel pour limiter le développement de bactéries résistantes aux antibiotiques. Étant donné que les dentistes prescrivent environ 8 % à 10 % de tous les antibiotiques prescrits en soins primaires dans les pays développés, la prescription dentaire peut contribuer à la résistance aux antibiotiques. Par conséquent, il est important que les antibiotiques ne soient utilisés que lorsqu'ils sont cliniquement bénéfiques pour la personne.

Caractéristiques des études

Les preuves sur lesquelles cette revue repose étaient à jour au 1er octobre 2013. Nous avons effectué des recherches dans les bases de données scientifiques et avons trouvé deux essais, avec 62 participants inclus dans l'analyse. Les deux essais ont été réalisés dans des écoles dentaires universitaires aux États-Unis et ont évalué l'utilisation d'antibiotiques oraux dans la réduction de la douleur et du gonflement rapportés par les adultes après avoir subi la première phase du traitement du canal radiculaire sous anesthésie locale. L'antibiotique utilisé dans les deux essais était la pénicilline VK et tous les participants avaient également reçu des analgésiques.

Principaux résultats

Les deux études incluses dans la revue ont indiqué qu'il n'y avait aucune différence claire dans la douleur ou le gonflement rapportés par les participants qui avaient reçu des antibiotiques par voie orale par rapport à un placebo (traitement fictif) lorsque les antibiotiques étaient utilisés en conjonction avec la première phase du traitement du canal radiculaire et les analgésiques, mais les études étaient de petite taille et nous n'avons pas pu exclure des différences potentiellement importantes entre les groupes. Aucune des deux études n'a examiné l'effet des antibiotiques administrés seuls, sans traitement dentaire.

Un essai a rapporté des effets secondaires chez les participants : une personne ayant reçu le placebo a eu une diarrhée et une personne ayant reçu des antibiotiques a ressenti de la fatigue et une baisse d'énergie après l'opération.

Qualité des preuves

Nous avons estimé que la qualité des preuves était très faible. Les preuves actuelles sont insuffisantes pour pouvoir déterminer les effets des antibiotiques dans ces conditions.

Notes de traduction

Traduit par: French Cochrane Centre 15th October, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Laički sažetak

Učinak antibiotika na zubobolju uzrokovanu upalom ili infekcijom korijena zuba u odraslih

Ovaj Cochrane sustavni pregled literature procijenio je učinke antibiotika na bol i oteklinu u dva stanja koja često uzrokuju zubnu bol, bez obzira na to jesu li antibiotici primijenjeni uz liječenje zuba (kao što je vađenje zuba, odvođenje gnoja (drenaža) iz otekline ili liječenje zubnoga kanala).

Dosadašnje spoznaje

Zubna bol je čest problem i može se razviti kada živac unutar zuba odumre zbog uznapredovalog karijesa ili teške ozljede. Tkivo koje se nalazi oko ruba korijena tada postaje upaljeno te može dovesti do akutne boli koja se pogoršava na zagriz. Bez liječenja bakterije mogu zaraziti mrtvi zub i uzrokovati gnojnu upalu u zubu (zubni apsces) koja uzrokuje oteklinu i širenje infekcije koja može i ugroziti život.

Preporučeno liječenje za taj oblik zubne boli jest uklanjanje mrtvoga živca i pridruženih bakterija. To se obično provodi vađenjem zuba ili liječenjem zubnog korijena. Antibiotici bi se trebali propisati jedino prilikom ozbiljne infekcije koja se proširila sa zuba. Međutim, neki stomatolozi još uvijek rutinski propisuju antibiotike koji se uzimaju na usta osobama s akutnim zubnim stanjima koji nemaju znakova širenja infekcije.

Smanjenje nepotrebnog propisivanja antibiotika važno je za ograničenje širenja bakterija otpornih na antibiotike. Stomatolozi propisuju 8% do 10% svih antibiotika u primarnoj praksi u razvijenim zemljama i tako mogu pridonijeti otpornosti bakterija na antibiotike. Stoga je iznimno važno koristiti antibiotike samo kada određenom pacijentu zaista mogu pomoći.

Značajke istraživanja

Dokazi na kojima se ovaj sustavni pregled temelji obuhvaćaju sve kliničke pokuse na tu temu objavljene do 1. listopada 2013. Autori su pretraživali znanstvene baze podataka i pronašli dva istraživanja s ukupno 62 ispitanika koja su uključena u analizu. Istraživanja su provedena na fakultetima dentalne medicine u SAD-u i u njima je ispitana korisnost oralnih antibiotika u smanjenju boli i oticanja u odraslih nakon prvog stadija liječenja kanala zubnog korijena u lokalnoj anesteziji. Antibiotik korišten u oba istraživanja bio je penicilin VK. Svi sudionici su također primali lijekove protiv boli.

Ključni rezultati

Dvije studije uključene u ovaj sustavni pregled literature pokazale su da nema jasnih razlika u boli ili oteklini u sudionika koji su koristili oralne antibiotike u usporedbi s placebom (lažno liječenje) kada se daju istodobno s prvom fazom liječenja zubnoga kanala i s lijekovima protiv boli. Međutim, ta istraživanja su bila mala te stoga rezultate tih studija treba uzeti s oprezom. Niti jedna od te dvije studije nije ispitivala učinak samih antibiotika bez liječenja zuba.

Jedna je studija opisala nuspojave u sudionika: jedna osoba koja se liječila placebom imala je proljev, a jedna osoba koja je primala antibiotike opisala je nakon operacije umor i nedostatak energije.

Kvaliteta dokaza

Kvaliteta dokaza procijenjena je kao vrlo niska. Trenutačno nema dovoljno dokaza koji bi mogli odrediti učinke antibiotika u tim stanjima.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Ozana Glibota
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

Ringkasan bahasa mudah

Kesan antibiotik terhadap sakit gigi akibat keradangan atau jangkitan pada akar gigi dalam kalangan dewasa.

Ulasan Kumpulan Kesihatan Oral Cochrane ini bertujuan menilai kesan antibiotik terhadap sakit dan bengkak dalam dua keadaan lazim yang menyebabkan sakit gigi, akibat rawatan pergigian atau tanpa rawatan pergigian (misalnya cabutan, penyaliran bengkak atau rawatan kanal akar).

Latarbelakang

Sakit gigi adalah masalah lazim dan boleh timbul apabila saraf dalam gigi mati akibat kerosakan berterusan atau trauma yang teruk.Tisu disekeliling hujung akar mengalami keradangan dan menyebabkan sakit akut yang bertambah teruk apabila menggigit. Tanpa rawatan, bakteria boleh menjangkiti gigi yang mati dan menyebabkan abses, dan membawa kepada bengkak dan jangkitan boleh merebak dan meragut nyawa.

Rawatan yang disyorkan untuk sakit gigi seperti ini adalah pembuangan saraf yang mati dan bakteria. Ini lazim dilakukan dengan cabutan gigi atau rawatan kanal akar.Antibiotik hanya diberi apabila terdapat jangkitan teruk yang telah merebak.Namun, sesetengah doktor gigi memberi antibiotik oral secara rutin kepada pesakit yang mengalami sakit gigi akut yang tiada tanda-tanda jangkitan merebak.

Pengurangan pemberian antibiotik yang tidak wajar memain peranan utama dalam menghadkan pembentukan baktera resistan antibiotik. Oleh kerana doktor gigi memberi 8% hingga 10% dari antibiotik penjagaan primer di negara maju, preskripsi pergigian boleh menyumbang kepada rintangan antibiotik.Oleh itu, adalah penting untuk antibiotik digunakan hanya apabila terdapat manfaat klinikal untuk seseorang.

Ciri-ciri kajian

Bukti ulasan ini adalah terkini sehinga 1 Oktober 2013. Kami mencari pangkalan data saintifik dan mendapati dua kajian yang melibatkan 62 peserta untuk analisis. Kedua-dua kajian dilaksanakan di sekolah pergigian universiti Amerika Syarikat dan menilai penggunaan antibiotik oral untuk mengurangkan sakit dan bengkak yang dilaporkan oleh orang dewasa selepas peringkat pertama rawatan kanal akar dengan penggunaan anestesia setempat.Antibiotik yang diguna dalam kedua-dua kajian ialah penisilin VK dan semua peserta juga menerima ubat penahan sakit.

Keputusan utama

Kedua-dua kajian tersebut melaporkan tiada perbezaan nyata tentang sakit dan bengkak yang dilaporkan oleh peserta yang menerima antibiotik oral berbanding plasebo (rawatan semu) apabila diberi sejurus peringkat pertama rawatan kanal akar bersama ubat penahan sakit, tetapi kajian adalah kecil dan kami tidak dapat mengetepikan perbezaan kumpulan yang berpotensi penting.Kedua-dua kajian tidak menilai kesan antibiotik yang diambil sendiri tanpa rawatan pergigian.

Satu kajian melaporkan kesan sampingan dalam kalangan peserta: seorang yang menerima ubat plasebo mengalami cirit-birit dan seorang lagi yang mnerima antibiotik mengalami keletihan dan kurang tenaga selepas pembedahan.

Kualiti bukti

Kami menilai kualiti bukti sebagai sangat rendah. Masa kini masih kekurangan bukti untuk menentukan kesan antibiotik dalam keadaan-keadaan tersebut.

Catatan terjemahan

Diterjemahkan oleh Noorliza Mastura Ismail (Kolej Perubatan Melaka-Manipal).Disunting oleh Tan May Loong,(Penang Medical College) Untuk sebarang pertanyaan mengenai terjemahan ini, sila hubungi noorliza.mastura@manipal.edu.my

Summary of findings(Explanation)

Summary of findings for the main comparison. Systemic antibiotics with a surgical intervention and analgesics for the management of symptomatic apical periodontitis and acute apical abscess in adults
  1. 1 One study with high risk of bias and small group sizes.
    2One study with unclear risk of bias and small group sizes.
    3 Different surgical interventions employed. Participants in one study had partial or total pulpectomy (there was no way of distinguishing between the two treatment modalities) while participants in the other all had total pulpectomy.
    4 Re-expressed from the standardised mean difference into the short ordinal numerical scale used by Henry 2001. Results should be interpreted with caution since back-translation of the effect size is based on the results of only one study.

Systemic antibiotics with a surgical intervention and analgesics for the management of symptomatic apical periodontitis and acute apical abscess in adults
Patient or population: adults with a symptomatic necrotic tooth or localised acute apical abscess (no signs of spreading infection or systemic involvement)
Settings: university dental schools, USA
Intervention: systemic antibiotics, partial or total pulpectomy and analgesics
Comparison: matched placebo, partial or total pulpectomy and analgesics
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Matched placebo, partial or total pulpectomy and analgesics Systemic antibiotics, partial or total pulpectomy and analgesics
Pain at 24 hours
Short ordinal numerical scale. Scale from: 0 to 3
The mean pain at 24 hours ranged across control groups from:
1.0 to 1.68
The mean pain at 24 hours in the intervention groups was
0.03 lower
(0.53 lower to 0.47 higher)
-61
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
-
Pain at 48 hours
Short ordinal numerical scale. Scale from: 0 to 3
The mean pain at 48 hours ranged across control groups from:
0.8 to 0.95
The mean pain at 48 hours in the intervention groups was
0.32 higher
(0.22 lower to 0.86 higher)
-61
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
-
Pain at 72 hours
Short ordinal scale. Scale from: 0 to 3
The mean pain at 72 hours ranged across control groups from:
0.3 to 0.82
The mean pain at 72 hours in the intervention groups was
0.08 higher
(0.38 lower to 0.54 higher)
-61
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
-
Swelling at 24 hours
Different short ordinal numerical scales
The mean swelling at 24 hours in the control groups was
0.59 4
The mean swelling at 24 hours in the intervention groups was
0.27 standard deviations higher
(0.23 lower to 0.78 higher)
-62
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
This converts back into a 36% increase (95% CI 31% decrease to 105% increase) of control mean for antibiotics (based on 1 study at unclear risk of bias)
Swelling at 48 hours
different short ordinal numerical scales
The mean swelling at 48 hours in the control groups was
0.73 4
The mean swelling at 48 hours in the intervention groups was
0.04 standard deviations higher
(0.47 lower to 0.55 higher)
-61
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
This converts back into a 4% increase (95% CI 49% decrease to 58% increase) of control mean for antibiotics (based on 1 study at unclear risk of bias)
Swelling at 72 hours
different short ordinal numerical scales
The mean swelling at 72 hours in the control groups was
0.59 4
The mean swelling at 72 hours in the intervention groups was
0.02 standard deviations higher
(0.49 lower to 0.52 higher)
-61
(2 studies)
⊕⊝⊝⊝
very low 1,2,3
This converts back to into a 2% increase (95% CI 55% decrease to 59% increase) of control mean for antibiotics (based on 1 study at unclear risk of bias)
Adverse effectsDuring the 3-day follow-up period in Fouad 1996, 1 participant in the placebo group reported diarrhoea and 1 participant in the antibiotic group reported fatigue and reduced energy postoperatively
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval.
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Dental pain can have a considerable detrimental effect on an individual's social functioning and quality of life (Reisine 1995; Pau 2005). In the Adult Dental Health Survey of 2009 conducted in the UK, 29% of individuals reported experiencing dental pain 'occasionally' or 'fairly/very often' during the preceding 12 months. Within the survey, prevalence of dental pain was 9%, with higher values reported for younger individuals and among lower socioeconomic groups (Steele 2011). Of these individuals, approximately 30% will be have symptomatic apical periodontitis and a further 13% will have an acute apical abscess (Sindet-Pedersen 1985; Estrela 2011).

Apical periodontitis arises following injury to the pulpal tissues of a tooth due to dental caries, tooth fracture, trauma or iatrogenic damage. While the dental pulp can recover from reversible pulpitis resulting from a mild to moderate injury, persistent or extensive damage results in irreversible levels of inflammation within the pulpal tissues. Should this occur, people may experience symptoms of irreversible pulpitis. Without treatment, irreversibly inflamed teeth then undergo pulpal necrosis and bacterial colonisation of the root canal system (Abbott 2004; Bergenholtz 2010).

Apical periodontitis (also known as periapical periodontitis) is an inflammatory lesion of the periradicular tissues that arises principally due to the egress of irritants such as bacteria and toxins from an inflamed or necrotic pulp (Torabinejad 1994). Its evolutionary role is protective: to contain the root canal bacteria and prevent the spread of infection. While the vast majority of cases are asymptomatic, exacerbations of apical periodontitis can present as symptomatic apical periodontitis or an acute apical abscess (Bergenholtz 2010).

Symptomatic apical periodontitis can arise either from a formerly healthy tooth that has subsequently undergone pulpal breakdown or from a tooth with a previously asymptomatic apical periodontitis. It is characterised by a dull or throbbing pain that is exacerbated by biting. The affected tooth usually has a negative or delayed positive response to vitality testing and is often highly sensitive to percussive forces (Bergenholtz 2010).

It should be noted that in determining the health of pulpal tissues, the term 'vitality testing' is commonly used. True 'vitality' tests attempt to examine the presence of pulp blood flow, while 'sensibility' tests employ the use of thermal or electrical stimuli to elicit a response from innervated tissue (Chen 2009). Although neither can definitively indicate the health of the dental pulp, they remain useful diagnostic aids, commonly used in both clinical practice and scientific studies.

Acute apical abscesses develop in the presence of a pre-existing apical periodontitis (Carrotte 2004). Persistent presence of infective material within the pulpless root canal system and around the apex of a tooth can lead to a massive influx of polymorphonuclear leukocytes into the periradicular tissues, leading to tissue liquefaction and pus formation (Bergenholtz 2010). Also known as a periapical, dentoalveolar or alveolar abscess, an apical abscess is characterised by the accumulation of pus in the periradicular tissues and can present as either an acute or chronic lesion. People with acute apical abscesses complain of a rapid onset, spontaneous pain, tenderness of the tooth to pressure, pus formation and swelling of associated tissues (Glickman 2009). Left untreated, the abscess may spread resulting in a serious, potentially life-threatening head and neck infection accompanied by fever, malaise and lymph node involvement (Abbott 2004). Since symptomatic apical periodontitis and acute apical abscess represent a continuum of the same disease process, it is appropriate to consider both conditions in this review (Sutherland 2004).

Description of the intervention

Clinical guidelines recommend that the first-line treatment for teeth with either symptomatic apical periodontitis or an acute apical abscess is the removal of the source of inflammation or infection by local, operative measures (Glenny 2004; SDCEP 2011). This involves either the extraction of the offending tooth, extirpation (removal) of the pulpal tissues, possibly in combination with the incision and drainage of any swelling present. Systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic symptoms (fever, malaise) (SDCEP 2011; Palmer 2012).

Several studies appear to indicate that antibiotics do not reduce the pain or swelling arising from teeth with symptomatic apical pathology in the absence of evidence of systemic involvement (Fouad 1996; Henry 2001). Nevertheless, 69% of individuals attending a British out-of-hours dental clinic with symptomatic apical periodontitis received a prescription for systemic antibiotics, many in the absence of a surgical intervention (Dailey 2001). Furthermore, the authors of the paper suggested that clinicians providing emergency dental treatment may be prescribing antibiotics as the first-line treatment for people with dental pain (Dailey 2001). In a survey of Spanish oral surgeons, over 70% reported that they would prescribe systemic antibiotics for people with moderate to severe pre-operative symptoms from a tooth with a necrotic pulp and acute apical periodontitis (Segura-Egea 2010). Comparatively, in a survey of members of the American Association of Endodontists, only 54% of respondents reported that they would prescribe antibiotics for the same condition, highlighting differences between practitioners of nationalities and specialities (Yingling 2002).

How the intervention might work

Doctors and dentists may prescribe systemic antibiotics to minimise the signs and symptoms of symptomatic apical periodontitis or acute apical abscess, and to treat or prevent the development of a serious orofacial swelling with systemic involvement. Antibiotics can be prescribed as an adjunctive or stand-alone treatment. People prescribed antibiotics may be given analgesics at the same time.

Why it is important to do this review

There is international concern about the overuse of antibiotics and the emergence of antibiotic-resistant bacterial strains (World Health Organization 2000). Since approximately 8% to 10% of antibiotics dispensed in primary care in developed countries are prescribed by a dentist, it is important not to underestimate the potential contribution of the dental profession to the development of antibiotic resistance (Al-Haroni 2007; Holyfield 2009; Prescribing and Primary Care Services 2013). Inappropriate use of antibiotics not only drives antibiotic resistance and misuses resources, it increases the risk of potentially fatal anaphylactic reactions and exposes people to unnecessary side effects (Gonzales 2001; Costelloe 2010). Furthermore, antibiotic prescribing for common medical problems increases patient expectations for antibiotics, leading to a vicious cycle of increased prescribing in order to meet expectations (Little 1997; Coenen 2006).

If systemic antibiotics are effective in the treatment of symptomatic apical periodontitis or acute apical abscess then it is important that the nature of any benefits be quantified. However, if antibiotics are ineffective, people may be unnecessarily exposed to harmful side effects and the increased possibility of developing antibiotic-resistant bacterial colonies. It is important that antibiotics be prescribed for dental conditions only when they are likely to result in clinical benefit for the person. Therefore, the objective of this review was to evaluate the effects of systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

Objectives

To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis or acute apical abscess in adults.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs) with parallel group design in the review. We excluded cluster RCTs.

Types of participants

Studies of adults (over the age of 18 years), male or female, who presented with a single tooth with a clinical diagnosis of either symptomatic apical periodontitis or acute apical abscess.

Types of interventions

Active intervention

Administration of any systemic antibiotic (either oral or intravenous) at any dosage prescribed in the symptomatic phase of apical periodontitis or acute apical abscess (with or without analgesics, and with or without surgical intervention (extraction, incision and drainage or endodontic treatment).

Control

Administration of a matched placebo prescribed in the symptomatic phase of apical periodontitis or acute apical abscess (with or without analgesics, and with or without surgical intervention).

Types of outcome measures

Primary outcomes
  1. Measures of participant-reported pain and swelling, gauged on either a continuous scale, such as visual analogue scale (VAS), or using binary or dichotomous outcomes.

  2. Clinician-reported measures of infection, such as swelling, temperature, trismus (reduced mouth opening), regional lymphadenopathy or cellulitis. These outcomes may have be reported as continuous, categorical or dichotomous variables.

Secondary outcomes
  1. Participant-reported quality of life measures.

  2. Type, dose and frequency of analgesics used.

  3. Any adverse effects or harm (hypersensitivity or other reactions) attributed to antibiotics or analgesics, complications of surgical treatment or hospitalisations.

Search methods for identification of studies

For the identification of studies included or considered for this review, we developed a detailed search strategy for each database searched. These were based on the search strategy developed for MEDLINE but revised appropriately for each database to take account of differences in controlled vocabulary and syntax rules.

The search strategy combined the subject search with the Cochrane Highly Sensitive Search Strategy for identifying reports of RCTs (2008 revision), as published in Box 6.4.c in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011) (Higgins 2011). The subject search used a combination of controlled vocabulary and free text-terms based on the search strategy for searching MEDLINE. The search of EMBASE was linked to the Cochrane Oral Health Group filters for identifying RCTs.

Electronic searches

We searched the following databases:

  • Cochrane Oral Health Group's Trials Register (to 1 October 2013);

  • Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9);

  • MEDLINE via OVID (1946 to 1 October 2013);

  • EMBASE via OVID (1980 to 1 October 2013);

  • CINAHL via EBSCO (1980 to 1 October 2013).

See Appendix 1 for details of all search strategies used. All databases were searched from their inception to October 2013 and we applied no restrictions on language of publication in the electronic searches.

Searching other resources

We searched the following trials registers for ongoing studies:

  • World Health Organization (WHO) International Trials Registry Platform (to 1 October 2013) (www.who.int/ictrp/en/);

  • US National Institutes of Health Trials Registry (ClinicalTrials.gov) (to 1 October 2013).

We searched for grey literature using the following resources:

  • OpenGrey (to 1 October 2013);

  • ZETOC Conference Proceedings (1993 to 1 October 2013).

We checked the reference lists of all included and excluded studies to identify any further trials.

Data collection and analysis

Selection of studies

Two review authors (Anwen Cope (AC) and Mala Mann (MM)) independently assessed the titles and abstracts (where available) of the articles identified by the search strategy and made decisions regarding eligibility. Full-text versions were obtain for all articles being considered for inclusion, as were those with insufficient information in the title or abstract to make a clear decision. We resolved any disagreements by discussion. We excluded studies later found not to meet the inclusion criteria and recorded them in the Characteristics of excluded studiestable.

Data extraction and management

We entered study details into the Characteristics of included studies table. AC and MM independently extracted the outcome data from the included studies using a standard data extraction form. The review authors discussed the results and resolved any disagreements by discussion or with a third review author (Ivor G Chestnutt (IGC)). In cases where uncertainties persisted, we contacted the study authors for clarification.

We extracted the following characteristics of the studies.

  1. Study methodology: study design, methods of allocation, method of randomisation, randomisation concealment, blinding, time of follow-up, loss to follow-up, country conducted in, number of centres, recruitment period and funding source.

  2. Participants: sampling frame, diagnostic criteria, inclusion criteria, exclusion criteria, number of participants in each group, baseline group demographics and clinical diagnosis.

  3. Intervention: type of antibiotic, dose, frequency and duration of course. Information about co-interventions, for example, surgical treatment or analgesia.

  4. Outcomes: primary outcomes at 24, 48 and 72 hours and seven days, and secondary outcomes as previously described (seePrimary outcomes; Secondary outcomes).

Assessment of risk of bias in included studies

Two review authors (AC and MM) independently assessed the risk of bias of the included studies and resolved any disagreements by discussion with a third review author (IGC). We completed a 'Risk of bias' table for each included study following the recommended methods for assessing the risk of bias in studies included in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This was a two-part tool addressing specific key domains including sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting and other bias. We tabulated relevant information describing what happened, as reported in the study or revealed by correspondence with the study authors, for each included study, along with a judgement of low, high or unclear risk of bias for each individual domain.

A summary assessment of the risk of bias of each included study was made as follows:

  • low risk of bias (plausible bias unlikely to seriously alter the results) if we assessed all key domains to be at low risk of bias;

  • unclear risk of bias (plausible bias that raises some doubt about the results) if we assessed one or more key domains as unclear;

  • high risk of bias (plausible bias that seriously weakens confidence in the results) if we assessed one or more key domains to be at high risk of bias.

We completed a 'Risk of bias' table for each included study. We also presented the results graphically.

Measures of treatment effect

For dichotomous outcomes, we expressed the estimate of effect of the intervention as risk ratios (RR) together with 95% confidence intervals (CI). For continuous outcomes (such as mean VAS scores), we reported mean differences (MD) (or standardised mean differences (SMD) when different scales measuring the same concept) and their corresponding 95% CI.

Unit of analysis issues

We anticipate that, by the nature of the outcome variables being recorded, studies included in future updates may involve repeat observations. Results from more than one time point for each study cannot be combined in a standard meta-analysis without a unit-of-analysis error. Therefore, we assessed outcomes at 24, 48 and 72 hours and seven days postoperatively, as the data allowed.

We included no clustered trials in the review.

Given the nature of the conditions and intervention under review, it is high unlikely any cross-over trials will be suitable for inclusion in the future.

In updates, we will consider multi-arm studies for inclusion in the review, in accordance with recommendations in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), we will combine all relevant experimental groups and considered them as a single group and compared them with a combined group of all the control groups, if present.

Dealing with missing data

We contacted the original investigators in cases of missing data.

Assessment of heterogeneity

We planned to assess heterogeneity using the Chi2 test (P value < 0.10 regarded as statistically significant). For studies judged as clinically homogeneous, we test heterogeneity using the I2 statistic, as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The I2 statistic describes the percentage of variability in effect estimates that is due to heterogeneity rather than sampling error. An I2 of 0% to 40% might not be important, 30% to 60% may represent moderate heterogeneity, 50% to 90% may have substantial heterogeneity and 75% to 100% studies has substantial heterogeneity.

Assessment of reporting biases

We examined within-study selective outcome reporting as a part of the overall risk of bias assessment and contacted study authors for clarification.

If there had been at least 10 studies included in a meta-analysis, we would have assessed between-study reporting bias by creating a funnel plot of effect estimates against their standard errors. If we had found asymmetry of the funnel plot by inspection and confirmed this by statistical tests, we would have considered possible explanations and taken into account in the interpretation of the overall estimate of treatment effects.

Data synthesis

We only carried out meta-analysis where studies of similar comparisons, reported similar outcomes, for people with similar clinical conditions. We combined MDs (or SMDs where studies had used different scales) for continuous outcomes, and combined RRs for dichotomous outcomes, using a fixed-effect model if there were only two or three studies, or a random-effects model if there were four or more studies.

Subgroup analysis and investigation of heterogeneity

We planned to investigate clinical heterogeneity by examining the following subgroups should sufficient data have been available.

  1. Different antibiotic class (e.g. penicillins versus macrolides).

  2. The effects of accompanying surgical intervention (extraction, incision and drainage or endodontic treatment).

Sensitivity analysis

Provided there were sufficient studies for each outcome and intervention, we had planned to undertake sensitivity analysis based on trials judged to be of low risk of bias.

Presentation of main results

We developed a 'Summary of findings' table for the primary outcomes of this review using GRADEPro software, with the GRADE assessment of the quality of the body of evidence.

Results

Description of studies

Results of the search

After de-duplication, electronic searches yielded 625 references. We identified one additional trial by checking the bibliographies of the selected trials and reviews (Al-Belasy 2003). After examination of the titles, and abstracts where available, we excluded 590 references from further analysis. We obtained full-text copies of the remaining 36 studies, translated them where required, and subjected them to further evaluation. At this stage, we excluded 34 studies and recorded their characteristics (Characteristics of excluded studies; Figure 1).

Figure 1.

Study flow diagram.

Included studies

Two randomised controlled trials (RCTs) satisfied the inclusion criteria (Fouad 1996; Henry 2001). See Characteristics of included studies table for further details.

Characteristics of trial designs and settings

Both studies were of parallel group design, one had three arms (Fouad 1996), and the other had two arms (Henry 2001). Both studies were conducted at university dental schools in the USA and were based at a single centre. One study was supported by a university research fund and the other did not declare funding sources. Neither study reported sample size calculations.

Characteristics of participants

We included 62 participants in the analysis for this review, with 21 people analysed in Fouad 1996, and 41 people analysed in Henry 2001. Both studies were conducted on otherwise healthy adults. Participants in one study had a mean age of 36.0 years (standard deviation (SD) 13.7 years) and had a clinical diagnosis of acute apical abscess with pulpal necrosis, periapical pain or swelling, or both (Additional Table 1; Fouad 1996). Participants in the other study had a mean age of 37 years (SD 16.5 years) in the penicillin arm and 38 years (SD 18.8 years) in the placebo arm (Additional Table 2; Henry 2001). All had a symptomatic necrotic tooth with a periapical radiolucency and no mucosal sinus tract (Henry 2001). One trial had more male participants (Fouad 1996) and the other had similar numbers of male and female participants (Henry 2001). There were no significant differences in the intra-study baseline characteristics of participants (Additional Table 1; Additional Table 2).

Table 1. Baseline characteristics for penicillin and placebo trial arms (Fouad 1996)
  1. M: men; n: number in group; SD: standard deviation; W: women.
    Unpublished data from personal communication.
    * Gender of 1 participant not recorded.
    ** Gender of 2 participants not recorded.

Trial arm Penicillin (n = 13) Placebo (n = 15) P value
Gender4W:8M*6W:7M**-
Mean age in years (SD)34.92 (17.33)37.17 (9.40)0.696
Mean baseline pain (SD)2.40 (1.08)2.00 (1.10)0.410
Mean baseline swelling (SD)1.91 (1.51)2.00 (1.48)0.866
Table 2. Baseline characteristics for penicillin and placebo trial arms (Henry 2001)
  1. M: men; n: number in group; SD: standard deviation; W: women.

Variable Penicillin (n = 19) Placebo (n = 22) P value
Age in years (SD)37 (16.5)38 (18.8)0.884
Gender10W:9M10W:12M0.647
Weight in pounds (SD)172 (28.4)170 (41.3)0.874
Estimated lesion area in mm (SD)14.0 (16.5)24.8 (22.6)0.105
Median baseline pain (SD)2.00 (2.00)2.00 (1.00)0.463
Median baseline percussion pain (SD)2.00 (2.00)2.00 (2.00)0.868
Median baseline swelling (SD)1.00 (2.00)0 (1.00)0.097
Characteristics of intervention
Objective 1: systemic antibiotics versus a matched placebo provided in conjunction with a surgical intervention

In one trial, participants underwent total or partial pulpectomy under local anaesthesia with temporary restoration at the baseline visit (Fouad 1996). In the other trial, all participants underwent total pulpectomy with temporary restoration at the baseline visit (Henry 2001).

In the study by Fouad 1996, participants in the penicillin group received oral penicillin (phenoxymethyl) VK 1 g following treatment and then 500 mg, every six hours for seven days. Participants in the placebo group received an oral matched placebo taken according to the same regimen. In the trial by Henry 2001, participants in the penicillin group received oral penicillin VK tablets (Wyeth Laboratories, Philadelphia, PA) 500 mg, every six hours for seven days and participants in the placebo group received an oral matched placebo (lactose) taken according to the same regimen.

In one trial, all participants also received ibuprofen 600 mg immediately before treatment, on four occasions during the next 24 hours and then as required (Fouad 1996). In the other trial, all participants received a bottle of ibuprofen 200 mg tablets (Advil, Whitehall Laboratories, New York, NY) with instructions to take two tablets every four to six hours as required. Each participant also received a labelled bottle of paracetamol (acetaminophen) with codeine (Tylenol #3, McNeil Consumer Products, Fort Washington, PA) with dosing instructions, to take if two ibuprofen did not relieve their discomfort. One participant was given Percocet (oxycodone plus paracetamol (acetaminophen)) instead (Henry 2001).

Objective 2: systemic antibiotics versus a matched placebo provided without a surgical intervention

We found no studies comparing systemic antibiotics versus a matched placebo provided without a surgical intervention.

Heterogeneity of interventions

There was heterogeneity with respect to the operative treatment, doses of antibiotics given to participants in the intervention arms and type, dose and frequency of analgesics provided to participants between the two studies.

Characteristics of the outcome measures
Primary outcomes

Both studies reported participant-reported pain. Both utilised a short ordinal numerical scale graded from 0 to 3. In Fouad 1996, this score was determined by converting the value from a VAS on the post-treatment card into a whole number rank. Pain was measured at the following data points in each study:

  • six hours, 12 hours, 24 hours, 48 hours and 72 hours (Fouad 1996);

  • day one, day two, day three, day four, day five, day six, day seven (Henry 2001).

Both studies reported participant-reported swelling. In Henry 2001, investigators utilised a short ordinal numerical scale graded from 0 to 3. In Fouad 1996, increase or decrease in swelling compared with baseline was recorded on a short ordinal numerical scale graded from 0 to 4. Swelling was measured at the following data points in each study:

  • six hours, 12 hours, 24 hours, 48 hours and 72 hours (Fouad 1996);

  • day one, day two, day three, day four, day five, day six, day seven (Henry 2001).

One study included percussion pain (Henry 2001). This was measured on a short ordinal numerical scale graded from 0 to 3.

One study included incidence of endodontic flare-up (Fouad 1996). This was measured dichotomously and was clinician-assessed based on the presence of: no relief or an increase in the severity of pain; no resolution or an increase in the size of swelling, fever, trismus or difficulty swallowing; signs of a drug allergy or any other abnormal symptoms.

Secondary outcomes

One study included the number and type of analgesics required (Henry 2001). In Fouad 1996, participants recorded whether they required additional analgesia; however, this information was not reported and was not available after contacting the investigators.

One study reported adverse effects (Fouad 1996).

Handling of data/data assumptions made in the review

For objective 1, we compared pain and swelling scores at 24, 48 and 72 hours and seven days postoperatively. For the purposes of the analysis, we made the assumption that the data points from Henry 2001 (day one, day two and day three) were sufficiently analogous to those measure in Fouad 1996 to be combined.

Excluded studies

We excluded the majority of references as they were not RCTs. Other excluded studies did not report relevant health outcomes, had no placebo control or had other characteristics that did not satisfy the inclusion criteria (see Characteristics of excluded studies table).

Risk of bias in included studies

The review authors' judgements about each risk of bias item for each included study are given in Figure 2.

Figure 2.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Randomisation

We considered both studies to be at low risk of bias for random sequence generation.

Allocation concealment

We assessed both studies to have adequate concealment of allocation prior to assignment. In Fouad 1996, individuals enrolling participants into the trial were not aware of the upcoming allocation sequence; envelopes were sequentially numbered, opaque and sealed; envelopes for the penicillin and placebo groups were identical in appearance and weight and were only opened after being assigned to the participant. In Henry 2001, participants were given sequentially numbered drug containers of identical appearance in accordance with the randomisation sequence produced prior to the experiment.

Blinding

We judged both studies to have employed adequate measures to ensure that active and placebo tablets had identical appearance, and, therefore, we considered risk of performance bias to be low for both studies. Similarly, we considered both studies to have low risk of detection bias as blinding was unlikely to have been broken.

Incomplete outcome data

We considered Fouad 1996 to be at high risk of attrition bias. Rates of withdrawal were in excess of 20% in across groups, with higher rates of withdrawal from the placebo than the penicillin group. We judged differential attrition as likely to be related to treatment outcomes. In Henry 2001, we were unable to judge risk of bias due to insufficient reporting of relative attrition rates and reasons for withdrawal and, therefore, this risk for this domain is 'unclear'.

Selective reporting

We judged one study to be at unclear risk of reporting bias, as investigators did not report whether the need for additional analgesia differed between the two trial arms, although this information was collected on the post-treatment card (Fouad 1996). There was no evidence of selective reporting within Henry 2001 and all expected outcomes were presented. We judged this study to be at low risk of reporting bias.

Other potential sources of bias

We judged both trials to be at low risk of other potential sources of bias.

Overall risk of bias

One study had high overall risk of bias (Fouad 1996), and one had unclear risk of bias (Henry 2001) (Figure 2).

Effects of interventions

See: Summary of findings for the main comparison Systemic antibiotics with a surgical intervention and analgesics for the management of symptomatic apical periodontitis and acute apical abscess in adults

Objective 1: systemic antibiotics versus a matched placebo provided in conjunction with a surgical intervention

Two studies, one at unclear risk of bias (Henry 2001), and one at high risk of bias (Fouad 1996), provided data for this comparison. Both compared oral penicillin VK against a matched placebo when provided alongside partial or total pulpectomy for adults with localised acute apical abscess or symptomatic necrotic tooth in otherwise healthy adults.

Primary outcomes
Pain

The analysis of participant-reported pain at data points 24, 48 and 72 hours was based on data from two studies (61 participants), one at high risk of bias (Fouad 1996), and one at unclear risk of bias (Henry 2001). Analysis of the seven-day time point was based on data from one study (41 participants) at unclear risk of bias (Henry 2001).

For the antibiotic group:

  • mean difference (MD) at 24 hours -0.03 (95% confidence interval (CI) -0.53 to 0.47);

  • MD at 48 hours 0.32 (95% CI -0.22 to 0.86);

  • MD at 72 hours 0.08 (95% CI -0.38 to 0.54);

  • MD at seven days -0.05 (95% CI -0.41 to 0.30, P value = 0.77).

Swelling

The analysis of participant-reported swelling at data points 24 hours (61 participants), 48 hours (62 participants) and 72 hours (61 participants) was based on data from two studies, one at high risk of bias (Fouad 1996), and one at unclear risk of bias (Henry 2001). Analysis of seven-day time point was based on data from one study at unclear risk of bias (Henry 2001). Standardised mean difference (SMD) was used to combine the different scales used for the 24-, 48- and 72-hour data points.

For the antibiotic group:

  • SMD at 24 hours 0.27 (95% CI -0.23 to 0.78). This converts back into a 36% increase (95% CI 31% decrease to 105% increase) of control mean for antibiotics. Re-expressed from the SMD into the short ordinal numerical scale used by Henry 2001. Results should be interpreted with caution since back-translation of the effect size was based on the results of only one study.

  • SMD at 48 hours 0.04 (95% CI -0.47 to 0.55). This converts back into a 4% increase (95% CI 49% decrease to 58% increase) of control mean for antibiotics. Re-expressed from the SMD into the short ordinal numerical scale used by Henry 2001. Results should be interpreted with caution since back-translation of the effect size was based on the results of only one study.

  • SMD at 72 hours 0.02 (95% CI -0.49 to 0.52). This converts back into a 2% increase (95% CI 55% decrease to 59% increase) of control mean for antibiotics. Re-expressed from the SMD into the short ordinal numerical scale used by Henry 2001. Results should be interpreted with caution since back-translation of the effect size was based on the results of only one study.

  • MD at seven days 0.02 (95% CI -0.28 to 0.32, P value = 0.90)

Percussion pain

The analysis of participant-reported percussion data at data points 24, 48 and 72 hours was based on data from one study (41 participants) at unclear risk of bias (Henry 2001).

For the antibiotic group:

  • MD at 24 hours -0.32 (95% CI -0.85 to 0.21, P value = 0.24);

  • MD at 48 hours 0.09 (95% CI -0.44 to 0.62, P value = 0.74);

  • MD at 72 hours 0.05 (95% CI -0.55 to 0.65, P value = 0.87);

  • MD at seven days 0.06 (95% CI -0.29 to 0.41, P value = 0.73).

Endodontic flare-up

The analysis of clinician-assessed incidence of endodontic flare-up over three-day follow-up period was based on data from one study at high risk of bias (20 participants) (Fouad 1996).

For the antibiotic group:

  • risk ratio (RR) of endodontic flare-up 0.27 (95% CI 0.01 to 4.90, P value = 0.37).

Secondary outcomes
Analgesics

The analysis of the number of analgesic tablets required during the seven-day follow-up period was based on data from one study (41 participants) at unclear risk of bias (Henry 2001).

For the antibiotic group:

  • MD for total number of ibuprofen tablets 1.58 (95% CI -4.55 to 7.71, P value = 0.62).

  • MD for total number of paracetamol (acetaminophen) with codeine tablets -0.31 (95% CI -3.94 to 3.32, P value = 0.87).

Adverse effects

During the three-day follow-up period in Fouad 1996 (20 participants, high risk of bias), one participant in the placebo group reported diarrhoea and one participant in the antibiotic group reported fatigue and reduced energy postoperatively.

Objective 2: systemic antibiotics versus a matched placebo provided without a surgical intervention

We found no studies comparing systemic antibiotics versus a matched placebo provided without a surgical intervention.

Discussion

Summary of main results

The review process identified two studies suitable for inclusion, both of which assessed the effects of penicillin VK compared with a matched placebo in adults with localised apical abscess or a symptomatic necrotic tooth (no signs of spreading infection or systemic involvement) when provided in conjunction with partial or total pulpectomy conducted under local anaesthesia and analgesics. There were no statistically significant differences in primary outcomes (participant-reported pain, swelling or percussion pain or incidence of endodontic flare-up) or secondary outcomes (analgesic use or incidence of adverse events) between participants who had received antibiotics and participants who had received a matched placebo. We considered this body of evidence (two studies, one at unclear risk of bias and one at high risk of bias) to be of very low quality and it should be interpreted with caution.

We found no studies that reported the effects of systemic antibiotics versus a matched placebo for symptomatic apical periodontitis when provided in conjunction with a surgical intervention. We found no studies that reported the effects of systemic antibiotics versus a matched placebo for symptomatic apical periodontitis or acute apical abscess when provided without a surgical intervention.

Overall completeness and applicability of evidence

We employed a comprehensive search strategy and we are confident that the majority of published trials are included in this review. We made efforts to identify all relevant studies and excluded no studies due to language.

The two included trials partially addressed the first of the two objectives (Fouad 1996; Henry 2001), which both investigated the effect of systemic antibiotics for acute apical abscess or symptomatic necrotic tooth provided in conjunction with total or partial pulpectomy in adults. However, there were no trials that assessed the effects of antibiotics for symptomatic apical periodontitis when used in conjunction with a surgical intervention. Furthermore, we found no trials assessing the second objective, which sought to compare antibiotics and a placebo for symptomatic apical periodontitis or acute apical abscess when provided without a surgical intervention.

The participants included in the two trials can be considered broadly representative of people who would consult a dentist due to an acute apical abscess or symptomatic necrotic tooth who do not have evidence of spreading infection or systemic involvement - participants came from a wide age range, were about equal gender mix and the majority had moderate pain at the baseline visit. However, both the trials excluded participants with co-morbidities or who may have been immunocompromised. Therefore, the results of this review may not be generalisable to a group of people who may be at higher risk of infection. While future trials should endeavour to obtain the most representative sample possible, it is unlikely to be feasible or ethical to conduct placebo-controlled trials in these groups of people.

One trial excluded participants with signs of spreading infection and systemic involvement (Fouad 1996), and the other trial included only a small number of participants with evidence of severe infections at baseline (Henry 2001). Therefore, the results of this review may or may not be generalisable to people with severe swelling or other signs of spreading infection or systemic involvement.

Both of the included studies were conducted at university dental schools and, in both trials, endodontic treatment was completed by practitioners who either worked in the Department of Endodontics (Fouad 1996), or were senior endodontic graduate students (Henry 2001). It would be reasonable to consider that both groups of practitioners had endodontic skills in excess of those of an average primary care dentist. The specialist settings in which the trials were conducted were unlikely to face the time constraints encountered in routine clinical practice. Therefore, the intervention provided within these studies may only have limited applicability to the treatment routinely provided at emergency appointments in general dental practice, where treatment decisions are often dictated by time pressures (Palmer 2000). Therefore, more trials in a primary care setting would enhance the evidence base for answering the questions posed by this review.

We found no trials assessing the effect of other surgical interventions, such as dental extraction or incision and drainage of a swelling. Since dental extraction is a common treatment for both symptomatic apical periodontitis and acute apical abscess, and incision and drainage of acute apical abscess is also frequently undertaken, the effects of these interventions could be considered in future trials.

The outcomes reported by the two trials measured the harms as well as the benefits of interventions. This is important as antibiotics can have adverse effects such as hypersensitivity reactions and gastrointestinal upset. Many of the outcome measures in the two included trials were participant-centred, such as pain, percussion pain and swelling. Since both pain and discomfort are known to impact an individual's quality of life (Skevington 1998), future trials should also consider formally measuring oral health-related quality of life outcomes to assess the beneficial and harmful effects of this intervention in more detail.

Quality of the evidence

The quality of the evidence, as summarised in Summary of findings for the main comparison for the main comparison, was rated as very low.

Given the considerable number of antibiotics prescribed by dentists to adults with acute dental conditions and the problems associated with indiscriminate use of antibiotics, the paucity of high-quality trials evaluating the effects of systemic antibiotics in the management of symptomatic apical periodontitis and acute apical abscess is disappointing. Only two studies met the inclusion criteria for this review; we judged one to be at high risk of bias and the other to be of unclear risk of bias. Both had methodological flaws with respect to attrition bias and the overall quality of evidence was very low. Furthermore, small group sizes mean that both studies were likely to lack the statistical power to detect differences between intervention and placebo groups. Sample size calculations were not reported in either study. Therefore, caution should be exercised when interpreting the results presented in this review.

Potential biases in the review process

Two independent review authors extracted data and assessed the methodological quality of each study, minimising potential bias.

We are confident that the extensive literature search used in this review has captured relevant literature and minimised the likelihood that we missed any relevant trials.

In the event of incomplete or unclear reporting of trial data, we contacted the trial authors to obtain any unpublished data or clarification of results. We applied no language or publication restrictions in our search.

Despite these efforts, it must be acknowledged that there is a small possibility that there were additional studies (published and unpublished) that we did not identify. It is possible that additional literature searches, such as searching non-English language databases and handsearching relevant journals, would have found additional studies.

Agreements and disagreements with other studies or reviews

Systematic reviews of the emergency management of acute apical periodontitis and acute apical abscess in the permanent dentition were published in 2003 (Matthews 2003; Sutherland 2003). These reviews had wider inclusion criteria and included trials of analgesics, local pharmacotherapeutics and surgical interventions in addition to antibiotic trials. Sutherland 2003 concluded that "the use of antibiotics in the management of AAP [acute apical periodontitis] is not recommended" and Matthews 2003 recommended that "the use of antibiotics in the management of localized AAA [acute apical abscess] over and above establishing drainage of the abscess, is not recommended".

Authors' conclusions

Implications for practice

Based on the current available data, which are of very low quality, there was insufficient evidence to determine the effects of the administration of systemic antibiotics to adults with symptomatic apical periodontitis or acute apical abscess.

Since antibiotic use is recognised as a major contributor to antimicrobial resistance, dental professionals should be judicious in their use of these agents and should refer to evidence-based best practice guidelines when managing people with acute dental conditions.

Implications for research

Large-scale, adequately powered and well-designed randomised controlled trials are needed to clarify the effectiveness of systemic antibiotics in the treatment of symptomatic apical periodontitis and acute apical abscess. However, all future trials should be carefully designed to ensure the potential benefits of providing systemic antibiotics to participants outweigh risks associated with antibiotic usage, both adverse effects and the possible contribution to antibiotic resistance.

Future studies should consider both utilising validated participant- and clinician-reported outcome measures, and report results according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines (www.consort-statement.com/).

Acknowledgements

The authors acknowledge the following help in the conduct of the review.

  • Contact authors of the two included studies.

  • Anne Littlewood, Trials Search Co-ordinator and Feedback Editor of the Cochrane Oral Health Group, who provided invaluable support in constructing and running the search strategies.

  • Dr Rebecca Payle, Senior Lecturer in Medical Statistics at Cardiff University School of Dentistry, who gave advice on the statistical elements of the protocol.

  • Anwen Cope would like to acknowledge the financial support for her PhD research, received from a President's Research Scholarship from Cardiff University.

  • The assistance of several colleagues who helped with translating articles during the selection of studies.

Data and analyses

Download statistical data

Comparison 1. Pain
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Pain at 24 hours261Mean Difference (IV, Fixed, 95% CI)-0.03 [-0.53, 0.47]
2 Pain at 48 hours261Mean Difference (IV, Fixed, 95% CI)0.32 [-0.22, 0.86]
3 Pain at 72 hours261Mean Difference (IV, Fixed, 95% CI)0.08 [-0.38, 0.54]
4 Pain at 7 days1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Pain, Outcome 1 Pain at 24 hours.

Analysis 1.2.

Comparison 1 Pain, Outcome 2 Pain at 48 hours.

Analysis 1.3.

Comparison 1 Pain, Outcome 3 Pain at 72 hours.

Analysis 1.4.

Comparison 1 Pain, Outcome 4 Pain at 7 days.

Comparison 2. Swelling
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Swelling at 24 hours262Std. Mean Difference (IV, Fixed, 95% CI)0.27 [-0.23, 0.78]
2 Swelling at 48 hours261Std. Mean Difference (IV, Fixed, 95% CI)0.04 [-0.47, 0.55]
3 Swelling at 72 hours261Std. Mean Difference (IV, Fixed, 95% CI)0.02 [-0.49, 0.52]
4 Swelling at 7 days1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 2.1.

Comparison 2 Swelling, Outcome 1 Swelling at 24 hours.

Analysis 2.2.

Comparison 2 Swelling, Outcome 2 Swelling at 48 hours.

Analysis 2.3.

Comparison 2 Swelling, Outcome 3 Swelling at 72 hours.

Analysis 2.4.

Comparison 2 Swelling, Outcome 4 Swelling at 7 days.

Comparison 3. Percussion pain
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Percussion pain at 24 hours1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2 Percussion pain at 48 hours1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3 Percussion pain at 72 hours1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4 Percussion pain at 7 days1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 3.1.

Comparison 3 Percussion pain, Outcome 1 Percussion pain at 24 hours.

Analysis 3.2.

Comparison 3 Percussion pain, Outcome 2 Percussion pain at 48 hours.

Analysis 3.3.

Comparison 3 Percussion pain, Outcome 3 Percussion pain at 72 hours.

Analysis 3.4.

Comparison 3 Percussion pain, Outcome 4 Percussion pain at 7 days.

Comparison 4. Endodontic flare-up
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Incidence of endodontic flare-up1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 4.1.

Comparison 4 Endodontic flare-up, Outcome 1 Incidence of endodontic flare-up.

Comparison 5. Analgesics
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Total number of ibuprofen tablets1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2 Total number of paracetamol (acetaminophen) with codeine tablets1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 5.1.

Comparison 5 Analgesics, Outcome 1 Total number of ibuprofen tablets.

Analysis 5.2.

Comparison 5 Analgesics, Outcome 2 Total number of paracetamol (acetaminophen) with codeine tablets.

Appendices

Appendix 1. Search strategies

Cochrane Oral Health Group's Trials Register

From October 2013, searches of the Cochrane Oral Health Group's Trials Register were conducted for this review using the Cochrane Register of Studies and the search strategy below:

1 ((antibiotic* or anti-biotic* or "anti biotic*" or antibacterial* or anti-bacterial* or "anti bacterial*" or antiinfect* or anti-infect* or "anti infect*" or antimicrobial* or anti-microbial* or "anti microbial*"):ti,ab) AND (INREGISTER)
2 ((penicillin* or amoxicillin or amoxycillin or co-amoxiclav or ampicillin or erythromycin or clindamycin*):ti,ab) AND (INREGISTER)
3 ((doxycycline* or metronidazole or azithromycin or co-amoxiclav or oxytetracycline or cefalexin or cephalexin or cefradine or cephradine or clarithromycin):ti,ab) AND (INREGISTER)
4 ((tetracycline or actimoxi or amoxicilline or amoxil or BRL-2333 or clamoxyl or hydroxyampicillin or penamox or polymox or trimox or wymox or amoxi-clav or amoxi-clavulanate or augmentin or BRL-25000):ti,ab) AND (INREGISTER)
5 ((clavulanate or clavulin or coamoxiclav or spektramox or synulox or phenoxymethylpenicillin or apocillin or beromycin or berromycin or betapen or fenoxymethylpenicillin or "Pen VK" or "v-cillin K" or vegacillin or clont or danizol ):ti,ab) AND (INREGISTER)
6 ((trichazol* or trichapol or trivazol or satric or metrogyl or flagyl or gineflavir or metrodzhil or nidagyl or chlolincocin or chlorlincocin or cleocin or "dalacin c"):ti,ab) AND (INREGISTER)
7 (#1 or #2 or #3 or #4 or #5 or #6) AND (INREGISTER)
8 ((abscess* or periapical or peri-apical or “peri apical”):ti,ab) AND (INREGISTER)
9 (#7 and #8) AND (INREGISTER)

A previous search of the Cochrane Oral Health Group's Trials Register was conducted in June 2012, using the Procite software and the search strategy below:

((antibiotic* or anti-biotic* or "anti biotic*" or antibacterial* or anti-bacterial* or "anti bacterial*" or antiinfect* or anti-infect* or "anti infect*" or antimicrobial* or anti-microbial* or "anti microbial*" or penicillin* or amoxicillin or amoxycillin or co-amoxiclav or ampicillin or erythromycin or clindamycin* or doxycycline* or metronidazole or azithromycin or co-amoxiclav or oxytetracycline or cefalexin or cephalexin or cefradine or cephradine or clarithromycin or tetracycline or actimoxi or amoxicilline or amoxil or BRL-2333 or clamoxyl or hydroxyampicillin or penamox or polymox or trimox or wymox or amoxi-clav or amoxi-clavulanate or augmentin or BRL-25000 or clavulanate or clavulin or coamoxiclav or spektramox or synulox or phenoxymethylpenicillin or apocillin or beromycin or berromycin or betapen or fenoxymethylpenicillin or "Pen VK" or "v-cillin K" or vegacillin or clont or danizol or trichazol* or trichapol or trivazol or satric or metrogyl or flagyl or gineflavir or metrodzhil or nidagyl or chlolincocin or chlorlincocin or cleocin or "dalacin c") AND abscess* or periapical or peri-apical or “peri apical”))

Cochrane Central Register of Controlled Trials (CENTRAL)

#1 MeSH descriptor Anti-Infective Agents explode all trees
#2 MeSH descriptor Penicillins explode all trees
#3 (antibiotic* in All Text or anti-biotic* in All Text or "anti biotic*" in All Text)
#4 (antibacterial* in All Text or anti-bacterial* in All Text or "anti bacterial*" in All Text)
#5 (antiinfect* in All Text or anti-infect* in All Text or "anti infect*" in All Text)
#6 (antimicrobial* in All Text or anti-microbial* in All Text or "anti microbial*" in All Text)
#7 (penicillin* in All Text or amoxicillin in All Text or amoxycillin in All Text or co-amoxiclav in All Text or ampicillin in All Text or erythromycin in All Text or clindamycin* in All Text or doxycycline* in All Text or metronidazole in All Text or azithromycin in All Text or co-amoxiclav in All Text or oxytetracycline in All Text or cefalexin in All Text or cephalexin in All Text or cefradine in All Text or cephradine in All Text or clarithromycin in All Text or tetracycline in All Text)
#8 (actimoxi in All Text or amoxicilline in All Text or amoxil in All Text or BRL-2333 in All Text or clamoxyl in All Text or hydroxyampicillin in All Text or penamox in All Text or polymox in All Text or trimox in All Text or wymox in All Text or amoxi-clav in All Text or amoxi-clavulanate in All Text or augmentin in All Text or BRL-25000 in All Text or clavulanate in All Text or clavulin in All Text or coamoxiclav in All Text or spektramox in All Text or synulox in All Text)
#9 (phenoxymethylpenicillin in All Text or apocillin in All Text or beromycin in All Text or berromycin in All Text or betapen in All Text or fenoxymethylpenicillin in All Text or "Pen VK" in All Text or "v-cillin K" in All Text or vegacillin in All Text)
#10 (clont in All Text or danizol in All Text or trichazol* in All Text or trichapol in All Text or trivazol in All Text or satric in All Text or metrogyl in All Text or flagyl in All Text or gineflavir in All Text or metrodzhil in All Text or nidagyl in All Text)
#11 (chlolincocin in All Text or chlorlincocin in All Text or cleocin in All Text or "dalacin c" in All Text)
#12 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11)
#13 MeSH descriptor Periapical diseases explode all trees
#14 (dental* in All Text near/5 absces* in All Text)
#15 ( (tooth in All Text near/5 absces* in All Text) or (teeth in All Text near/5 absces* in All Text) )
#16 ( (periapical in All Text near/5 absces* in All Text) or (peri-apical in All Text near/5 absces* in All Text) or (apical in All Text near/5 absces* in All Text) )
#17 ( (periapical in All Text near/5 periodont* in All Text) or (peri-apical in All Text near/5 periodont* in All Text) or (apical in All Text near/5 periodont* in All Text) )
#18 ( (periapical in All Text near/5 inflam* in All Text) or (peri-apical in All Text near/5 inflam* in All Text) or (apical in All Text near/5 inflam* in All Text) )
#19 ( (periapical in All Text near/5 infect* in All Text) or (peri-apical in All Text near/5 infect* in All Text) or (apical in All Text near/5 infect* in All Text) )
#20 ( (dentoalveol* in All Text near/5 absces* in All Text) or (dento-alveol* in All Text near/5 absces* in All Text) or (alveol* in All Text near/5 absces* in All Text) )
#21 ( (periradicular in All Text near/5 absces* in All Text) or (peri-radicular in All Text near/5 absces* in All Text) or (radicular in All Text near/5 absces* in All Text) )
#22 (#13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21)
#23 (#12 and #22)

MEDLINE via OVID

1. exp Anti-Infective Agents/
2. exp Penicillins/
3. (antibiotic$ or anti-biotic$ or "anti biotic$").tw.
4. (antibacterial$ or anti-bacterial$ or "anti bacterial$").tw.
5. (antiinfect$ or anti-infect$ or "anti infect$").tw.
6. (antimicrobial$ or anti-microbial$ or "anti microbial$").tw.
7. (penicillin$ or amox?cillin or co-amoxiclav or ampicillin or erythromycin or clindamycin$ or doxycycline$ or metronidazole or azithromycin or co-amoxiclav or oxytetracycline or cefalexin or cephalexin or cefradine or cephradine or clarithromycin or tetracycline).tw.
8. (actimoxi or amoxicilline or amoxil or BRL-2333 or clamoxyl or hydroxyampicillin or penamox or polymox or trimox or wymox or amoxi-clav or amoxi-clavulanate or augmentin or BRL-25000 or clavulanate or clavulin or coamoxiclav or spektramox or synulox).tw.
9. (phenoxymethylpenicillin or apocillin or beromycin or berromycin or betapen or fenoxymethylpenicillin or "Pen VK" or "v-cillin K" or vegacillin).tw.
10. (clont or danizol or trichazol$ or trichapol or trivazol or satric or metrogyl or flagyl or gineflavir or metrodzhil or nidagyl).tw.
11. (chlolincocin or chlorlincocin or cleocin or "dalacin c").tw.
12. or/1-11
13. exp Periapical diseases/
14. (dental$ adj5 absces$).tw.
15. ((tooth or teeth) adj5 absces$).tw.
16. ((periapical adj5 absces$) or (peri-apical adj5 absces$) or (apical adj5 absces$)).tw.
17. ((periapical adj5 periodont$) or (peri-apical adj5 periodont$) or (apical adj5 periodont$)).tw.
18. ((periapical adj5 inflam$) or (peri-apical adj5 inflam$) or (apical adj5 inflam$)).tw.
19. ((periapical adj5 infect$) or (peri-apical adj5 infect$) or (apical adj5 infect$)).tw.
20. ((dentoalveol$ adj5 absces$) or (dento-alveol$ adj5 absces$) or (alveol$ adj5 absces$)).tw.
21. ((periradicular adj5 absces$) or (peri-radicular adj5 absces$) or (radicular adj5 absces$)).tw.
22. or/13-21
23. 12 and 22

The above subject search was linked to the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of theCochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0 (updated March 2011) (Higgins 2011).

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. drug therapy.fs.
6. randomly.ab.
7. trial.ab.
8. groups.ab.
9. or/1-8
10. exp animals/ not humans.sh.
11. 9 not 10

EMBASE via OVID

1. exp Antiinfective agent/
2. exp Penicillin derivate/
3. (antibiotic$ or anti-biotic$ or "anti biotic$").tw.
4. (antibacterial$ or anti-bacterial$ or "anti bacterial$").tw.
5. (antiinfect$ or anti-infect$ or "anti infect$").tw.
6. (antimicrobial$ or anti-microbial$ or "anti microbial$").tw.
7. (penicillin$ or amox?cillin or co-amoxiclav or ampicillin or erythromycin or clindamycin$ or doxycycline$ or metronidazole or azithromycin or co-amoxiclav or oxytetracycline or cefalexin or cephalexin or cefradine or cephradine or clarithromycin or tetracycline).tw.
8. (actimoxi or amoxicilline or amoxil or BRL-2333 or clamoxyl or hydroxyampicillin or penamox or polymox or trimox or wymox or amoxi-clav or amoxi-clavulanate or augmentin or BRL-25000 or clavulanate or clavulin or coamoxiclav or spektramox or synulox).tw.
9. (phenoxymethylpenicillin or apocillin or beromycin or berromycin or betapen or fenoxymethylpenicillin or "Pen VK" or "v-cillin K" or vegacillin).tw.
10. (clont or danizol or trichazol$ or trichapol or trivazol or satric or metrogyl or flagyl or gineflavir or metrodzhil or nidagyl).tw.
11. (chlolincocin or chlorlincocin or cleocin or "dalacin c").tw.
12. or/1-11
13. exp Tooth periapical disease/
14. (dental$ adj5 absces$).tw.
15. ((tooth or teeth) adj5 absces$).tw.
16. ((periapical adj5 absces$) or (peri-apical adj5 absces$) or (apical adj5 absces$)).tw.
17. ((periapical adj5 periodont$) or (peri-apical adj5 periodont$) or (apical adj5 periodont$)).tw.
18. ((periapical adj5 inflam$) or (peri-apical adj5 inflam$) or (apical adj5 inflam$)).tw.
19. ((periapical adj5 infect$) or (peri-apical adj5 infect$) or (apical adj5 infect$)).tw.
20. ((dentoalveol$ adj5 absces$) or (dento-alveol$ adj5 absces$) or (alveol$ adj5 absces$)).tw.
21. ((periradicular adj5 absces$) or (peri-radicular adj5 absces$) or (radicular adj5 absces$)).tw.
22. or/13-21
23. 12 and 22

The above subject search was linked to the Cochrane Oral Health Group filter for identifying randomised controlled trials in EMBASE via OVID:

1. random$.ti,ab.
2. factorial$.ti,ab.
3. (crossover$ or cross over$ or cross-over$).ti,ab.
4. placebo$.ti,ab.
5. (doubl$ adj blind$).ti,ab.
6. (singl$ adj blind$).ti,ab.
7. assign$.ti,ab.
8. allocat$.ti,ab.
9. volunteer$.ti,ab.
10. CROSSOVER PROCEDURE.sh.
11. DOUBLE-BLIND PROCEDURE.sh.
12. RANDOMIZED CONTROLLED TRIAL.sh.
13. SINGLE BLIND PROCEDURE.sh.
14. or/1-13
15. (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
16. 14 NOT 15

CINAHL via EBSCO

S1 (MH "Antiinfective Agents+")
S2 (MH "Penicillins+")
S3 (antibiotic* or anti-biotic* or "anti biotic*")
S4 (antibacterial* or anti-bacterial* or "anti bacterial*")
S5 (antiinfect* or anti-infect* or "anti infect*")
S6 (antimicrobial* or anti-microbial* or "anti microbial*")
S7 (penicillin* or amoxicillin or amoxycillin or co-amoxiclav or ampicillin or erythromycin or clindamycin* or doxycycline* or metronidazole or azithromycin or co-amoxiclav or oxytetracycline or cefalexin or cephalexin or cefradine or cephradine or clarithromycin or tetracycline)
S8 (actimoxi or amoxicilline or amoxil or BRL-2333 or clamoxyl or hydroxyampicillin or penamox or polymox or trimox or wymox or amoxi-clav or amoxi-clavulanate or augmentin or BRL-25000 or clavulanate or clavulin or coamoxiclav or spektramox or synulox)
S9 (phenoxymethylpenicillin or apocillin or beromycin or berromycin or betapen or fenoxymethylpenicillin or "Pen VK" or "v-cillin K" or vegacillin)
S10 (clont or danizol or trichazol* or trichapol or trivazol or satric or metrogyl or flagyl or gineflavir or metrodzhil or nidagyl)
S11 (chlolincocin or chlorlincocin or cleocin or "dalacin c")
S12 S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11
S13 (MH "Periapical Diseases")
S14 (dental* N5 absces*)
S15 ((tooth N5 absces*) or (teeth N5 absces*))
S16 ((periapical N5 absces*) or (peri-apical N5 absces*) or (apical N5 absces*))
S17 ((periapical N5 periodont*) or (peri-apical N5 periodont*) or (apical N5 periodont*))
S18 ((periapical N5 inflam*) or (peri-apical N5 inflam*) or (apical N5 inflam*))
S19 ((periapical N5 infect*) or (peri-apical N5 infect*) or (apical N5 infect*))
S20 ((dentoalveol* N5 absces*) or (dento-alveol* N5 absces*) or (alveol* N5 absces*))
S21 ((periradicular N5 absces*) or (peri-radicular N5 absces*) or (radicular N5 absces*))
S22 S13 or S14 or S15 or S16 or S17 or S18 or S19 or S20 or S21
S23 S12 and S22

World Health Organization (WHO) International Clinical Trials Registry Platform

dental abscess AND antibiotic
dental abscess AND penicillin
dental abscess AND antibacterial
dental abscess AND antimicrobial
dental abscess AND antiinfectious
periapical abscess AND antibiotic
periapical abscess AND penicillin
periapical abscess AND antibacterial
periapical abscess AND antimicrobial
periapical abscess AND antiinfectious

US National Institutes of Health Trials Registry (ClinicalTrials.gov)

dental abscess* AND antibiotic*
dental abscess* AND penicillin*
dental abscess* AND antibacterial*
dental abscess* AND antimicrobial*
dental abscess* AND antiinfect*
periapical abscess* AND antibiotic*
periapical abscess* AND penicillin*
periapical abscess* AND antibacterial*
periapical abscess* AND antimicrobial*
periapical abscess* AND antiinfect*

OpenGrey

dental abscess* AND antibiotic*
dental abscess* AND penicillin*
dental abscess* AND antibacterial*
dental abscess* AND antimicrobial*
dental abscess* AND antiinfect*
periapical abscess* AND antibiotic*
periapical abscess* AND penicillin*
periapical abscess* AND antibacterial*
periapical abscess* AND antimicrobial*
periapical abscess* AND antiinfect*

ZETOC Conference Proceedings

dental abscess* AND antibiotic*
dental abscess* AND penicillin*
dental abscess* AND antibacterial*
dental abscess* AND antimicrobial*
dental abscess* AND antiinfect*
periapical abscess* AND antibiotic*
periapical abscess* AND penicillin*
periapical abscess* AND antibacterial*
periapical abscess* AND antimicrobial*
periapical abscess* AND antiinfect*

Contributions of authors

  • Anwen Cope initiated the review, drafted the protocol, extracted the data, performed risk of bias assessment and wrote the final review.

  • Nick Francis and Fiona Wood initiated the review, made amendments to the protocol and were involved in writing the final review.

  • Ivor Chestnutt initiated the review, made amendments to the protocol, was the arbiter during study selection and data extraction, and was involved in writing the final review.

  • Mala Mann drafted the protocol, extracted the data, performed risk of bias assessment and was involved in writing the final review.

Declarations of interest

Anwen Cope, Nick Francis, Fiona Wood, Mala Mann, Ivor Chestnutt: no interests to declare.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Wales School for Primary Care Research, UK.

    Financial support for this project was provided by the Wales School for Primary Care Research.

  • Cochrane Oral Health Group Global Alliance, UK.

    All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Association of Oral Surgeons, UK; British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; British Society of Periodontology, UK; Canadian Dental Hygienists Association, Canada; Mayo Clinic, USA; National Center for Dental Hygiene Research & Practice, USA; New York University College of Dentistry, USA; and Royal College of Surgeons of Edinburgh, UK) providing funding for the editorial process (http://ohg.cochrane.org/).

  • National Institute for Health Research (NIHR), UK.

    CRG funding acknowledgement:
    The NIHR is the largest single funder of the Cochrane Oral Health Group.

    Disclaimer:
    The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.

Differences between protocol and review

  • We have made a minor alteration to the objectives to specify the difference between antibiotics provided with a surgical intervention and those without.

  • We used a fixed-effect model in the meta-analysis not a random-effects model as specified by the protocol. This was because fewer trials were suitable for inclusion than we initially anticipated.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Fouad 1996

Methods

RCT

Number of centres: 1 (Department of Endodontics, University of Iowa, USA)

Recruitment period: 3.5 years

Design: parallel group 3-arm RCT

Participants

Adults presenting for emergency treatment

Group 1 (penicillin)

Mean age 34.92 years (SD 17.33 years). Gender: 4 women, 8 men (1 gender not recorded). Mean baseline pain (SD): 2.40 (1.08). Mean baseline swelling (SD): 1.91 (1.51)

Group 2 (placebo)

Mean age 37.17 years (SD 9.40 years). Gender: 6 women, 7 men (2 gender not recorded). Mean baseline pain (SD): 2.00 (1.10). Mean baseline swelling (SD): 2.00 (1.48)

Included participants had a clinical diagnosis of acute apical abscess with pulpal necrosis with periapical pain or swelling, or both

Participants were excluded if they had: elevated temperature (above 37.8 ºC (100 ºF); malaise; fascial space involvement; allergy to penicillin or cephalosporins; diseases or medications compromising the immune system; renal failure or any other significant renal or hepatic impairment; people who had taken antibiotics in the 2-week period prior to their visit; pregnant or lactating or taking oral contraceptives

Number of participants at randomisation: group 1 = 13; group 2 = 15

Number of participants included in the analysis: group 1 = 10; group 2 = 11

Interventions

Endodontic treatment: all participants had the affected tooth treated by total or partial pulpectomy on day 0. This involved delivery of local anaesthesia, assessment of the tooth, determination of working length, partial/total cleaning and shaping of the canals with copious irrigation with 2.6% sodium hypochlorite. Canals were dried and calcium hydroxide paste applied and the access cavity temporised with CavitTM (a light-cured temporary sealing compound for temporary restoration of cavities) or IRM® (intermediate restorative material is a polymer-reinforced zinc oxide-eugenol composition restorative material designed for intermediate restorations). Some participants also underwent incision and drainage of a localised intraoral swelling, if judged to be clinically indicated

Participants were then assigned to a trial arm:

Group 1: oral penicillin (phenoxymethyl) VK 500 mg, 1 g after endodontic treatment followed by 500 mg 6-hourly for 7 days

Group 2: oral matched placebo taken according to the same regimen

Group 3: neither medication group

Analgesics: all participants received ibuprofen 600 mg immediately before treatment, 4 times daily for 24 hours and then as needed

Outcomes

Primary outcomes

Participants were required to complete a post-treatment card recording their experiences up to 3 days postoperatively. This card was then returned to the authors via post. Pain was assessed using a VAS, which was then converted into a short ordinal numerical scale from 0 to 3: 0 indicated pain of no clinical significance; 1 = mild pain; 2 = moderate pain; 3 = severe pain. Postoperative swelling relief was recorded on a simple categorical scale ('no swelling', 'much less', 'slightly less', 'same', 'slightly more') with participants required to compare current levels of swelling to those they had experienced preoperatively. The categorical scale was then given scores from 0 to 4: 0 = no swelling; 1 = significant reduction in swelling; 2 = slight decrease in swelling; 3 = same size swelling as before; 4 = an increase in the size of swelling

Incidence of flare-up: measured dichotomously and was clinician-assessed based on the presence of: no relief or an increase in the severity of pain; no resolution or an increase in the size of swelling, fever, trismus or difficulty swallowing; signs of a drug allergy or any other abnormal symptoms

Secondary outcomes

Incidence of participant-reported side effects; type and frequency of additional analgesic medication

Notes

Funding source: not stated

Sample size calculation: not stated

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "A statistician provided random numbers" (email from author)

Comment: the participants appeared to be equally distributed between the penicillin and placebo groups

Allocation concealment (selection bias)Low riskAuthor confirmed that there was no way for the individual(s) enrolling participants into the trial to know the upcoming allocation sequence; study envelopes were sequentially numbered, opaque and sealed; and study envelopes were only opened once the participant was enrolled onto the trial
Blinding of participants and personnel (performance bias)
All outcomes
Low riskAuthor confirmed that the placebo looked exactly the same as the penicillin tablets
Blinding of outcome assessment (detection bias)
All outcomes
Low riskParticipants recorded the outcome measures and were blinded to their group assignment
Incomplete outcome data (attrition bias)
All outcomes
High risk

Following randomisation, there were 13 participants in the penicillin group and 15 in the placebo group. 3 participants in each group did not return their post-treatment card and were judged to have dropped out. A further 2 participants in the placebo group were withdrawn (1 at 6 hours and 1 at 24 hours) after returning with symptoms necessitating further treatment. The missing data related to these 2 participants was likely to be related to treatment outcomes (levels of pain or swelling, or both). Attrition for both arms of the trial was in excess of 20%, and was higher in the placebo than the penicillin group

Furthermore, following personal communication with trial authors, it was identified that there was incomplete baseline data (age, gender, baseline pain or swelling) for 5 study participants across the 2 trial arms. Since the numbers of participants recruited to each group were low, baseline characteristics of these 5 individuals may have led to differences between the penicillin and placebo groups

Selective reporting (reporting bias)Unclear riskPrimary outcome measures reported, 1 secondary outcome (additional analgesia) not reported
Other biasLow riskNo other sources of bias identified

Henry 2001

  1. a

    RCT: randomised controlled trial; SD: standard deviation; VAS: visual analogue scale.

Methods

RCT

Number of centres: 1 (The Ohio State University College of Dentistry, USA)

Recruitment period: not stated

Design: parallel group 3-arm RCT

Participants

Adults presenting for emergency treatment

Group 1 (penicillin)

Mean age 37 years (SD 16.5 years). Gender: 10 women, 9 men. Median baseline pain (SD): 2.00 (2.00). Median baseline percussion pain (SD): 2.00 (2.00). Median baseline swelling (SD): 1.00 (2.00)

Group 2 (placebo)

Mean age 38 years (SD 18.8 years). Gender: 10 women, 12 men. Median baseline pain (SD): 2.00 (1.00). Median baseline percussion pain (SD): 2.00 (2.00). Median baseline swelling (SD): 0 (1.00)

Included participants had a symptomatic necrotic tooth and actively had spontaneous pain. To be eligible the affected tooth had to test negative to an electric pulp test (Analytic Technology Corp., Redmond, WA) and ice; have a periapical radiolucency and not have had previous endodontic treatment. Included participants were in good health (as determined by written and verbal history), had not received antibiotics in the 30 days prior to enrolment to the trial and did not have a probable or actively draining sinus tract

Number of participants at randomisation: not stated in paper, approximately 51 (from personal communication)

Number of participants included in the analysis: group 1 = 19; group 2 = 22

Interventions

Endodontic treatment: all participants underwent total pulpectomy of the affected tooth on day 0. Canals were prepared using a step-back preparation and K-type files (L.D. Caulk, Inc., Milford, DE) and irrigated with 2.62% hypochlorite. Following instrumentation, canals were dried and a temporary restoration placed (CavitTM (a light-cured temporary sealing compound for temporary restoration of cavities))

Participants were then assigned to a trial arm

Group 1: oral penicillin (phenoxymethyl) VK 500 mg, 6-hourly for 7 days

Group 2: oral matched placebo taken according to the same regimen

Analgesics: all participants received a supply of ibuprofen and were advised to take 400 mg (2 x 200 mg tablets) every 4-6 hours, as required. Each participant also received a labelled bottle of paracetamol (acetaminophen) with codeine (30 mg), which they were instructed to take 1 or 2 tablets every 4 hours only if 2 ibuprofen tablets did not relieve their discomfort

Outcomes

Primary outcomes

Participant-reported pain, percussion pain and swelling experience at the baseline visit and upon rising for 7 days after treatment on categorical scales. Participants received a 7-day diary to record postoperative symptoms upon rising each day. This was returned at the obturation appointment (typically the end of root canal treatment). Pain was assessed using a short ordinal numerical scale from 0 to 3: 0 = no pain; 1 = mild pain; 2 = moderate pain; 3 = severe pain. Participants used the same scale to rate pain to percussion (achieve by tapping the affected tooth with a finger). Swelling was assessed on a similar ordinal numerical scale from 0 to 3: 0 = no swelling; 1 = mild swelling, a mild puffiness that was not bothersome; 2 = moderate swelling that caused facial distortion and was bothersome; 3 = a severe swelling that caused serious facial distortion and was very bothersome

Secondary outcomes

The number and type of pain medication taken

Notes

Funding source: Graduate Endodontic Student Research Fund and Goldberg Memorial Fund, Graduate Endodontics, College of Dentistry, The Ohio State University

Sample size calculation: not stated

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk 
Allocation concealment (selection bias)Low risk 
Blinding of participants and personnel (performance bias)
All outcomes
Low risk 
Blinding of outcome assessment (detection bias)
All outcomes
Low riskPrimary outcome measures were participant-assessed and it was highly unlikely blinding was broken
Selective reporting (reporting bias)Low risk 
Other biasLow risk 

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
  1. a

    RCT: randomised controlled trial.

Achard 1967Not an RCT
Al-Belasy 2003No placebo control
Alves 2000No placebo control
Angelini 1983Not an RCT
Anonymous 1968Not an RCT
Banoczy 1985Not an RCT
Baratieri 1968Not an RCT.
Brabant 1968Not an RCT
Brennan 2006Not all participants met inclusion criteria for clinical diagnosis. No subgroup data presented
Citoler Gutierrez 1969Not an RCT
Cumming 1984Not an RCT
D'Atri 1973Not an RCT
Davis 1969Sample included children
De Vries 1974Not an RCT
Deffez 1992No placebo control
Diamantes-Kepiotes 1974Intervention did not include a systemic antibiotic
Dolci 1982Not an RCT
Flood 1977Not an RCT
Gabka 1968Not an RCT
Groshikov 1970Not an RCT
Haapasalo 1986Not an RCT
Hood 1978Not an RCT
Hooley 1969Not an RCT
Khosla 1970Not an RCT
Krzywicki 1975Not an RCT
Lewis 1986No placebo control
Lin 2006Intervention did not include a systemic antibiotic
Lindeboom 2005Prevention study not fulfilling inclusion criteria
Lorber 1967Not an RCT
Matijevic 2009Sample included children
Nowakowska 1974Not an RCT
Oeda 1985No placebo control
Ranta 1988Not all participants met inclusion criteria for clinical diagnosis. No subgroup data presented
Re 1988No placebo control

Ancillary