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Antibiotics for acute laryngitis in adults

  1. Ludovic Reveiz1,*,
  2. Andrés Felipe Cardona2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 30 JAN 2013

DOI: 10.1002/14651858.CD004783.pub4


How to Cite

Reveiz L, Cardona AF. Antibiotics for acute laryngitis in adults. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD004783. DOI: 10.1002/14651858.CD004783.pub4.

Author Information

  1. 1

    Health Systems Based on Primary Health Care (HSS), Pan American Health Organization, Research Promotion and Development Team, Washington DC, USA

  2. 2

    Institute of Oncology, Fundación Santa Fe de Bogotá, Clinical and Translational Oncology Group, Bogotá, Cundinamarca, Colombia

*Ludovic Reveiz, Research Promotion and Development Team, Health Systems Based on Primary Health Care (HSS), Pan American Health Organization, 525, 23rd St, NW, Washington DC, 20037-2895, USA. mmreveiz@hotmail.com. lreveiz@yahoo.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions), comment added to review
  2. Published Online: 28 MAR 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Description of the condition

Upper respiratory tract infection (URTI) is the most common acute illness worldwide and is usually self diagnosed and self treated at home (Cherry 2003; McAvoy 1994). In 1995, URTI was the most frequent reason for seeking ambulatory care in the United States, resulting in more than 37 million visits to physician practitioners and emergency departments (Gonzales 2001a). It is also the most common reason for absence from work in the United States. Losses in income for employed persons, costs to employers with time lost from work, and costs of medical treatment amounted to USD 112 billion in 1997 (Birnbaum 2002).

Laryngeal inflammation may be due to many causes, such as viral infection, acid reflux, voice abuse, toxic inhalation, caustic ingestion, irritation from purulent sinus drainage, hypersensitivity reactions, immune disorders, or from coughing due to any cause (Koufman 1996).

Acute laryngitis is one of the most common pathologies identified in the larynx and can be defined as an inflammation of the larynx and vocal fold mucosa, lasting less than three weeks. Episodes are usually self limiting and are influenced by weather conditions (Danielides 2002; Vaughan 1982). Symptoms of acute laryngitis include a lowering of the normal pitch of the voice and hoarseness, which usually persist for three to eight days. Patients with laryngitis may also experience symptoms of an URTI, such as sore throat, odynophagia, rhinorrhoea, dyspnoea, postnasal discharge and congestion (Postma 1998; Schalen 1988; Spiegel 2000). Direct examination with a flexible nasolaryngoscope usually reveals secretions, erythema and oedema of the vocal folds.

Aetiology is not established in routine practice and the diagnosis can often be made by history alone. Unfortunately, there are no clinically useful criteria that help to distinguish between bacterial and viral infections (Vaughan 1982). Acute infectious laryngitis is usually caused by a viral infection. Respiratory viruses like parainfluenza, rhinovirus, influenza and adenovirus have been aetiologically associated with laryngitis (Higgins 1974; Postma 1998). However, bacterial pathogens such as Moraxella catarrhalis (M. catarrhalis), Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae) have been frequently isolated from the nasopharynx in adults with acute laryngitis (Hol 1996; Schalen 1980; Schalen 1988; Verduin 2002); another related pathogen is Chlamydia pneumoniae (C. pneumoniae) (Hashiguchi 1992).

 

Description of the intervention

URTIs represent one of the most common causes of antimicrobial use and a frequent reason for prescribing antibiotics in ambulatory practice and primary care (Cohen 2012; Gonzales 2001a; McAvoy 1994; McCaig 1995; Steinman 2003a; WHO 2003; Wirtz 2010). In adults with acute laryngitis, treatment is usually directed toward the control of symptoms with voice rest, analgesic therapy and humidification. Macrolides, cephalosporins, a combination of penicillins with beta-lactamase inhibitors, and extended-spectrum penicillins are also frequently prescribed (McGregor 1995; Steinman 2003a). In an observational study of the antibiotic prescribing behaviour of general practitioners in managing URTIs, 14.9% of antibiotic treatment courses were prescribed for treating laryngitis or tracheitis (Mazzaglia 1998). A retrospective analysis for a five-year period of 9.6 million physician office visits by patients with URTIs found that antibiotics were prescribed at more than 50% of visits (Sun 2006).

Reasons for over-prescribing antibiotics are varied but they often involve physicians' and patients' attitudes and expectations (Bertino 2002; Mazzaglia 1998; Steinman 2003a). A Cochrane systematic review evaluated the effectiveness of professional interventions in improving antibiotic prescriptions by healthcare providers in outpatient settings as well as the impact of these interventions on reducing the incidence of antimicrobial resistant pathogens. The authors concluded that a multi-faceted intervention, with educational interventions occurring at many levels, including repeated media campaigns, implementation of guidelines, and feedback to the profession on antibiotic prescribing data and resistance, may improve antibiotic prescribing behaviour and stop the increase in the prevalence of resistant pneumococci, H. influenzae and other microorganisms (Arnold 2005; Malmvall 2007). In addition, one study conducted in the United States found that antibiotic utilisation varies substantially among commercial health plans (Steinman 2009).

 

Why it is important to do this review

Concerns about the emergence and spread of antimicrobial resistance have been raised by the World Health Organization (WHO). Excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community, at a substantial cost to the healthcare system (Gonzales 2001a; Gonzales 2001b; Steinman 2003b). As the cost of medical treatment for laryngitis is high (Birnbaum 2002; Cohen 2012) and there is increasing concern over the resistance of common bacteria to commonly used antibiotics, there is a need to investigate the role of antibiotic drugs in acute laryngitis.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

To assess the effectiveness and safety of different antibiotic therapies in adults with acute laryngitis. A secondary objective was to report the rates of adverse events associated with these treatments.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomised controlled trials (RCTs) comparing antibiotic therapy with placebo or another antibiotic in the treatment of acute laryngitis.

 

Types of participants

We included adults with acute laryngitis, defined by the International Classification of Health Problems in Primary Care (ICHPPC) as hoarseness associated with other symptoms of URTI. We excluded participants with relevant chronic underlying diseases, those displaying symptoms of laryngitis for more than three weeks (chronic laryngitis) and those receiving antibiotic therapy within the two weeks preceding diagnosis.

 

Types of interventions

We included trials comparing antibiotics with placebo or antibiotics of a different class for acute laryngitis.

 

Types of outcome measures

 

Primary outcomes

 
Clinical improvement

  1. Improvement in recorded voice score assessed by an expert panel at presentation and after the period of time considered in each trial (usually one or two weeks, or both). As a standard, trials used the patient's normal voice, recorded weeks later.
  2. Symptom improvement at presentation (hoarseness/subjective voice score, pharyngitis, cough, sore throat and rhinorrhoea/nasal congestion) and after the period of time considered in each trial, as assessed by the investigators or the patient.

 

Secondary outcomes

 
Bacteriological findings

  1. Evaluated at the acute and the follow-up visits.

 
Adverse reactions following antibiotic therapy

  1. Serious adverse events, i.e. serious enough to require withdrawal from the treatment group.
  2. Minor adverse events reported by participants and not requiring withdrawal from the treatment group (gastrointestinal side effects such as diarrhoea, dyspepsia, abdominal pain and rash).

 
Laryngoscopic findings

  1. Evaluated at the acute and the follow-up visits.

 

Search methods for identification of studies

 

Electronic searches

For this 2013 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 12, part of The Cochrane Library, www.thecochranelibrary.com (accessed 30 January 2013), which includes the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (January 2011 to January week 3, 2013), EMBASE (January 2011 to January 2013), LILACS (January 2011 to January 2013) and BIOSIS (January 2011 to January 2013).

Details of the CENTRAL and MEDLINE search strategy are in Appendix 1. We combined the MEDLINE search with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision); Ovid format (Lefevbre 2011). We adapted the search strategy to search EMBASE (Appendix 2), LILACS (Appendix 3) and BIOSIS (Appendix 4). For details of earlier search strategies, see Appendix 5.

We imposed no language or publication restrictions.

 

Searching other resources

We employed other strategies including the searching of references of review articles; books related to infections of the respiratory tract; and handsearches of journals such as Journal of Infectious Diseases, Clinical Infectious Diseases, Journal of Antimicrobial Chemotherapy, Head and Neck, Otorhinolaryngology, Annals of Otology Rhinology and Laryngology and Scandinavian Journal of Infectious Diseases (for the 2008 update).

We searched grey literature such as conference abstracts/proceedings, published lists of theses and dissertations worldwide (dissertation abstract database), letters, government documents (CDC database) and other literature outside of the main journal literature, where possible (McAuley 2000).

We contacted some pharmaceutical companies to obtain unpublished trial data. We contacted leading researchers involved in the field by e-mail to obtain information on additional published and unpublished data and trials (for the 2008 update).

We also consulted local and international experts in the field and searched databases of ongoing trials registers such as the International Clinical Trials Registry Platform (ICTRP) search portal (http://www.who.int/trialsearch/Default.aspx).

 

Data collection and analysis

 

Selection of studies

Two review authors (LR, AC) independently retrieved the articles and assessed their eligibility from the title and abstracts.

 

Data extraction and management

Two review authors (LR, AC) independently assessed the full text of all studies identified as possibly relevant. The review authors were not blinded to the origin or conclusions of the article during eligibility assessment, data extraction or quality assessment (Berlin 1997).

 

Assessment of risk of bias in included studies

Two review authors (LR, AC) independently assessed the risk of bias for each study as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved disagreements by discussion. The possible sources of bias described below are considered and reflected in the 'Risk of bias' table for each included study. Whenever possible we included additional information with a clarifying comment or a quoted sentence taken directly from the original article.

We assessed the following domains as low risk of bias, unclear or high risk of bias:

  1. Generation of allocation sequence
  2. Allocation concealment
  3. Blinding (of participants, personnel and outcome assessors)
  4. Incomplete outcome data
  5. Selective reporting
  6. Other sources

 

(1) Generation of allocation sequence (checking for possible selection bias)

We described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

We assessed the method as follows.

  • Low risk (any truly random process, e.g. random number table; computer random number generator).
  • High risk (any non-random process, e.g. odd or even date of birth; hospital or clinic record number).
  • Unclear risk, if the trial was described as randomised, but the method used for the allocation sequence generation was not described.   

 

(2) Allocation concealment (checking for possible selection bias)

We described for each included study the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We assessed the methods as follows.

  • Low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes).
  • High risk (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth).
  • Unclear risk, if the trial was described as randomised, but the method used to conceal the allocation was not described.

 

(3) Blinding or masking (checking for possible performance bias)

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We judged studies at low risk of bias if they were blinded, or if we judged that the lack of blinding could not have affected the results. We assessed blinding separately for different outcomes or classes of outcomes.

We assessed the methods as follows.

  • Low risk, high risk or unclear for participants.
  • Low risk, high risk or unclear for personnel.
  • Low risk, high risk or unclear for outcome assessors.

 

(4) Incomplete outcome data (checking for possible attrition bias through withdrawals, drop-outs, protocol deviations)

We assessed the methods as follows.

  • Low risk (any one of the following): no missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.

  • High risk (any one of the following): reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

  • Unclear risk (any one of the following): insufficient reporting of attrition/exclusions to permit judgement of ‘low risk’ or ‘high risk’ (e.g. number randomised not stated, no reasons for missing data provided); the study did not address this outcome.

 

(5) Selective reporting bias (reporting bias due to selective outcome reporting)

We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We assessed the methods as follows.

  • Low risk (any one of the following): the study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way or the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

  • High risk (any one of the following): not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

  • Unclear risk: insufficient information to permit judgement of ‘low risk’ or ‘high risk’.

 

(6) Free of other bias (bias due to problems not covered elsewhere in the table)

We described for each included study any important concerns we have about other possible sources of bias (baseline imbalance, sponsorship bias, confirmation bias, bias of the presentation data, etc.)

  • Low risk of bias: the trial appears to be free of other components that could put it at risk of bias.
  • Unclear risk: the trial may or may not be free of other components that could put it at risk of bias.
  • High risk of bias: there are other factors in the trial that could put it at risk of bias, e.g. no sample size calculation made, academic fraud, industry involvement or extreme baseline imbalance.

 

(7) Overall risk of bias

We made explicit judgements about whether studies were at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors independently carried out data extraction using a previously designed form to ensure validity. Discrepancies were resolved by an open discussion between all review authors. The differences in the study participants, interventions and outcomes among the included trials are presented in the Characteristics of included studies table.

 

Measures of treatment effect

In future updates, we will assess the measurement of the intervention effect for dichotomous outcomes using the risk ratio (RR). We will assess the measurement of the intervention effect for continuous outcomes using the mean difference (MD).

 

Unit of analysis issues

We found no studies with non-standard designs, such as cross-over trials and cluster-randomised trials.

 

Dealing with missing data

In future updates, we will address missing data for dichotomous outcomes by an intention-to-treat (ITT) analysis. We will consider the potential impact of these missing data in the interpretation of the results of the review when necessary.

 

Assessment of heterogeneity

In future updates, we will assess heterogeneity using the I2 statistic. We will interpret the I2 statistic according to the following thresholds: less than 25% will be considered as low level heterogeneity; 25% to 50% as moderate level, and higher than 50% as high level heterogeneity (Higgins 2011).

We will explore potential sources of heterogeneity by means of a subgroup analysis when possible.

 

Assessment of reporting biases

For future updates, if there are 10 or more studies in the meta-analysis we will investigate reporting biases (such as publication bias) using funnel plots. We will assess funnel plot asymmetry visually and use formal tests for funnel plot asymmetry (Higgins 2011).

 

Data synthesis

For future updates, we will use fixed-effect meta-analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect, i.e. where trials are examining the same intervention and the trials’ populations and methods are judged sufficiently similar. We will use a random-effects meta-analysis if clinical heterogeneity is sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, to produce an overall summary if an average treatment effect across trials is considered clinically meaningful. We will treat the random-effects summary as the average range of possible treatment effects. If we use random-effects analyses, we will present the results as the average treatment effect with its 95% confidence interval, and the estimates of  the T2 and I2 statistic (Higgins 2011).

 

Subgroup analysis and investigation of heterogeneity

For future updates, we will perform subgroup analysis in order to investigate heterogeneity by studying the factors that contribute to clinical heterogeneity. We will perform subgroup analyses according to gender, age and different doses of antibiotics administered.

 

Sensitivity analysis

For future updates, we plan to carry out a sensitivity analyses according to 'Risk of bias' assessment (Higgins 2011).

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Results of the search

This is an updated version of the original review published in Issue 2, 2007 of The Cochrane Library (Reveiz 2007). From the results of the extensive literature searches, 3610 citations were initially identified as potentially relevant. We performed updated searches from June 2004 to December 2006, from December 2006 to November 2008, from October 2008 to February 2011 and from January 2011 to January 2013, resulting in 222 additional citations. Manual culling reduced this to three reports of possibly eligible trials. Only two trials fulfilled the criteria for inclusion (Schalén 1985; Schalén 1993) and a duplicated trial was excluded (Schalén 1992). Both studies were conducted by the same group of researchers in Sweden. Additional searches conducted to identify other relevant studies or unpublished data did not uncover any new trials. Although we identified 46 trials in the ICTRP database, no ongoing trials complied with the inclusion criteria.

 

Included studies

In a study of penicillin V in acute laryngitis in adults (Schalén 1985), 100 participants over 18 years of age were examined and recruited at the otolaryngology department of the University of Lund, Sweden to receive either penicillin V (800 mg two times a day for five days) or an identical placebo. No participants were reported to have dropped out or as having been lost to follow-up. Exclusion criteria included participants with relevant underlying diseases such as chronic bronchitis, pregnancy, antibiotic treatment within the preceding two weeks, and a history of penicillin allergy.

The trial measured the symptoms of hoarseness (subjective voice score), cough, rhinorrhoea and nasal congestion using self reported daily records collected in a questionnaire. A voice recording of standardised text was obtained for each patient at the first visit and subsequently at re-examinations at five to seven days, 10 to 14 days, and two to six months following the acute episode. The four recordings from each patient were presented in random order to four experienced voice specialists. The voice samples were evaluated with regards to 10 different qualities of voice (no further description of the quality of voice was provided). Each quality was evaluated individually by the members of the group using a quantitative score (0 = normal, 1 = slight aberration, 2 = abnormal) and the sum of each result was used to obtain an average score for the penicillin V and placebo groups. Microbiological specimens were collected from the nasopharynx and throat at the initial visit and one and two weeks later.

The second trial investigated erythromycin for treatment of acute laryngitis in adults (Schalén 1993). One hundred and six consecutive participants were recruited at the otolaryngology department of the University of Lund, Sweden, and 90 completed the double-blind trial. Six participants failed to keep scheduled appointments and one presented with an exanthema on the second day of antibiotic treatment. Participants lost to follow-up were not included in the analysis. Participants were randomised to receive either erythromycin ethylsuccinate (taken orally twice daily for five days) or placebo in identical tablets. The inclusion and exclusion criteria, outcomes and follow-up were the same as the first trial. However, a different voice score (0 = normal, 1 = slight aberration, 2 = moderate aberration, 3 = severe aberration) and 12 voice qualities (rough voice, diplophonia, breathiness, vocal fry, episodes of aphonia, registered abnormalities, registered breaks, sonority, hyperfunction and hypofunction, and high or low pitch) were used in the second trial.

 

Excluded studies

Only one study was excluded from the review (see Characteristics of excluded studies).

 

Risk of bias in included studies

We considered both studies to have unclear risk of bias (see Risk of bias in included studies, Figure 1 and Figure 2).

 FigureFigure 1. 'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
 FigureFigure 2. 'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study

In the penicillin V study (Schalén 1985), methods to generate the sequence of randomisation and allocation concealment were not reported. Furthermore, no description of the sample size or power calculation was recorded. Both the participants and treating physicians were blinded. However, the characteristics of this blinding were not described. No drop-outs or withdrawals were reported.

Information was given regarding baseline characteristics including gender, age, voice demand or abuse, smoker condition and previous laryngitis (three or more episodes during the preceding five years) making it easy to ascertain that the groups were sufficiently similar at the start of the trial. There were no statistically significant differences between the two groups in symptoms and clinical findings at the acute visits (in terms of preceding URTI, presence of rhinitis, cough and sore throat, abnormal findings like redness and oedema in the larynx, pharynx and epipharynx, mean voice score and bacterial pathogen isolated from the nasopharynx).

The mean interval between the start of vocal symptoms and the first evaluation was 3.6 days. However, the interval was longer for participants receiving antibiotics (3.8 ± 3.3) compared to the placebo (3.4 ± 3.0). All data were evaluated using a cross-tabulated Chi2 test and a probability level of 0.01 was considered significant.

The erythromycin study publication (Schalén 1993) stated that the trial was randomised and participants and physicians were blinded by using identical placebo tablets. A power calculation and intention-to-treat (ITT) analysis were not reported. Seven of 106 participants dropped out or withdrew from the study for specific reasons and were not accounted for in the trial analysis. Baseline characteristics of the participants appeared to be broadly similar between groups and included the same variables as the penicillin V study. As they were not described, we calculated P values for any differences in the population characteristics and the symptoms and signs at presentation and found no significant difference between the two groups.

The erythromycin group had a significantly higher proportion of bacterial pathogens and M. catarrhalis was isolated from the nasopharynx in this group (P = 0.045 and P = 0.012, Fisher's exact test), respectively. The mean interval between the start of vocal symptoms and the first evaluation was not reported. Non-parametric tests were used for statistical analysis. Fisher's exact probability test was used to compare bacterial elimination rates between the two groups and the Mann-Whitney U test with adjusted z was used for all other comparisons. A probability level of 5% was considered significant.

 

Allocation

We judged the methods of randomisation and allocation concealment to be unclear in both RCTs.

 

Blinding

Both trials were reported as "double blind". However, it was unclear if the methods to ensure blinding were effective. There was insufficient information to permit judgment of 'low risk' or 'high risk' on blinding of participants and personnel and blinding of the outcome assessment.

 

Incomplete outcome data

One trial had no drop-outs (Schalén 1985) and we judged it as having low risk of bias. In the other trial (Schalén 1993), 15% of participants were lost to follow-up and we judged it as having unclear risk of bias.

 

Selective reporting

We judged both trials as having unclear risk of bias.

 

Other potential sources of bias

Other potential sources of bias are summarised in the 'Risk of bias' tables.

 

Effects of interventions

 

Primary outcomes

 

1. Clinical improvement

In the penicillin V trial (Schalén 1985) the mean objective voice scores at the first visit and at re-examination after one and two weeks, as well as at follow-up after two to six months, did not differ significantly between the penicillin V and the placebo groups. Significant improvement was reported in the severity of reported vocal symptoms, nasal congestion/rhinorrhoea, throat symptoms, cough and laryngeal abnormalities evaluated by indirect laryngoscopy at the follow-up examinations in the control and intervention groups, as judged by the participants. Significant improvement measured by higher mean voice scores was found at the acute visits among participants with M. catarrhalis, H. influenzae or S. pneumoniae (26 ± 8) isolated from the nasopharynx, compared to results obtained for those with negative cultures (20 ± 10) (P < 0.05). However, the subjective voice scores at the acute visits did not differ between the participants harbouring the three mentioned pathogen isolates and those without the organisms. This study used parametric measures.

In the erythromycin trial (Schalén 1993) the mean objective voice scores at the first visit, at re-examination after one and two weeks, and at follow-up after two to six months, did not differ significantly between control and intervention groups. Thirty randomly selected voice samples recorded at presentation were evaluated and the Kendall coefficient of concordance between listeners for the voice qualities ranged from 0.45 to 0.91. (The Kendall's coefficient of concordance is a measure of the agreement among several judges who are assessing a given set of objects). After one week, the mean scores were clearly reduced and the voice profiles were essentially normalised in both groups.

At one week there were significant improvements in the severity of reported vocal symptoms, comparing erythromycin and placebo groups (P = 0.042), as judged by the participants. At two weeks, significantly fewer complaints of cough were reported by the erythromycin group compared to the placebo group (P = 0.031). The trialists compared signs of laryngitis, pharyngitis and rhinitis, evaluated by mirror endoscopy or direct inspection, and found no statistical differences between the two groups. This study used non-parametric statistics.

We did not aggregate results from the trials as there was significant heterogeneity between them, with different drugs and definitions of some outcomes.

 

Secondary outcomes

 

1. Bacteriological findings

In the penicillin V trial (Schalén 1985), M. catarrhalis, H. influenzae and S. pneumoniae were isolated from 50%, 15% and 1% of the participants respectively, at the first evaluation. The isolation rates of each of the mentioned pathogens at the acute and at the follow-up visits did not differ significantly between the two intervention groups.

In the erythromycin trial (Schalén 1993), M. catarrhalis was isolated from the nasopharynx in 50% of participants, H. influenzae in 20% of participants and S. pneumoniae in 5% of participants at the acute visit. After one week, M. catarrhalis was eliminated in 83% of the participants in the erythromycin group as compared with 32% in the placebo group (P < 0.001, Fisher's exact test). However, there was no difference between the two groups in the recovery rate of M. catarrhalis at two weeks.

 

2. Adverse drug reactions

No deaths were reported in either the penicillin V trial (Schalén 1985) or the erythromycin study (Schalén 1993). No adverse drug reactions were reported in the penicillin V trial (Schalén 1985) although it was unclear which potential toxic effects were monitored for. Only one patient was reported to present with an exanthema, on the second day of erythromycin treatment.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Summary of main results

Antibiotics appear to have no benefit in treating acute laryngitis; no differences were found in the so-called 'objective outcome'. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. We consider that these outcomes are not sufficient to justify the use of antibiotics in clinical practice. Treating laryngitis with conservative measures in the first instance is reasonable as it remains unclear that antibiotics are worthy and beneficial to individuals or populations.

 

Benefits of treatment

The effectiveness of antibiotic treatment for the common cold and for sore throat is covered in other Cochrane Reviews (Arroll 2010; Spinks 2011). Trials identified in those reviews included some participants with symptoms of acute laryngitis; conditions that affect the upper respiratory tract are not a single entity. As mentioned by Arroll et al, the review authors had to accept the clinical judgement of the trialists as to which participants were included in their upper respiratory tract infection (URTI) clinical trials (Arroll 2010).

Acute laryngitis may result from direct infection of the larynx, from irritation of the larynx due to coughing or from contact with infected secretions. Hence the supposition that acute laryngitis, along with other conditions that affect the upper respiratory tract, may not be related to one particular cause. Acute laryngitis is a self limiting condition that usually varies in duration from three to eight days. Considering that the time taken from the start of hoarseness to the visit reported in the penicillin V trial was 3.6 (± 3.2) days, most of the first re-examinations would have been done five to seven days later, when symptoms were likely to have disappeared.

Other outcomes, like reduction of illness time and absolute reduction averaged over the whole illness, were not estimated in the present trials. These clinically important outcomes and other outcomes, such as re-attendance or time off school or work, are probably at least as important as those that were used. It is important to state that the use of the voice score attempts to qualify different signs in a quantitative manner. This implies some subjectivity in assessing each score. Furthermore, the trial authors assumed that any difference from zero to one, or from one to two, was equally relevant, and that the 10 (or 12) signs analysed were also considered equally important (Altman 1999).

Erythromycin is apparently effective at reducing voice disturbances as measured by participants after one week and cough after two weeks. The authors considered that these findings suggested the usefulness of antibiotics in a special subgroup of people for whom voice function was essential to their professional or social activities, but their use appeared to be discretionary rather than mandatory. We calculated a risk ratio (RR) of 0.7 (95% confidence interval (CI) 0.51 to 0.96, P = 0.034) with a number needed to treat for an additional beneficial outcome (NNTB) of 4.5 for the subjective voice scores, considering total improvement as score '0' and partial or no improvement as the sum of scores 1, 2 and 3; for the cough after two weeks the RR was 0.38 (95% CI 0.15 to 1, P = 0.058).

The trials included only people with laryngitis who were admitted to the ear, nose and throat department, which may have lead to selection bias that favoured participants with severe symptoms. People with this condition will often not go to hospital or consult a primary care practitioner (Cherry 2003; McAvoy 1994). Another concern was information not collected by the trial authors, such as the concomitant use of other medications that may alter the course of illness, for example, decongestants, heated or humidified air, or voice rest, etc.

 

Adverse effects of treatment

Reporting on adverse effects of antibiotic use was irregular. Other studies described rare but severe adverse reactions, for example, hepatotoxicity, transient deafness and allergic reactions. Gastrointestinal symptoms represented the most frequent disturbance, occurring in 15% to 20% of participants on erythromycin. A significant number of drug interactions have also been reported (FDA 2004; Periti 1993).

 

Natural history and microbiological findings

Natural history and microbiological findings also support the non-use of antimicrobials. Almost 20 years ago bacterial pathogens such as M. catarrhalis and H. influenzae were implicated in the genesis of upper respiratory tract infection (URTI) and acute laryngitis. This conclusion was based on studies that confirmed that carriage of these pathogens is an uncommon feature in healthy adults (DiGiovanni 1987; Ejlertsen 1994; Schalen 1980).

The high nasopharyngeal isolation rates of M. catarrhalis (50% in both studies) and H. influenzae (15% in the penicillin V trial and 20% in the erythromycin trial) were apparently consistent with the use of antibiotics for this condition. However, after one week the voice profiles appeared to be essentially normalised in both antibiotic and placebo groups in both trials; no relevant differences were found in clinical symptoms assessed by the participants apart from the above described. These findings support the conclusion that the disorder is generally self limiting, and maybe the majority of participants in the studies were suffering from viral URTIs.

Isolates of M. catarrhalis, as reported by Schalén et al in both trials (Schalén 1985; Schalén 1993), were obtained from swabs placed in haematin agar tubes and inoculated onto haematin agar plates in 6% CO2 atmosphere as well as onto blood agar plates incubated anaerobically. M. catarrhalis, considered by the authors to be the principal bacterial pathogen related to acute laryngitis, was confirmed by fermentation reactions and by testing for species-specific protein antigen. If no growth was found, the swabs kept in the haematin agar tubes were streaked and incubated as above.

Over the years the following criteria have been used to clearly identify M. catarrhalis from other bacterial species: gram stain (Verduin 2002); colony morphology; lack of pigmentation of the colony on blood agar; oxidase production; DNAase production; failure to produce acid from glucose, sucrose, fructose, lactose and maltose; growth at 22°C on nutrient agar; failure to grow on modified Thayer-Martin medium; and, finally, reduction of nitrite and nitrate. Currently, the identity of this pathogen is best confirmed by positive reactions in at least three of the following tests, since none are 100% sensitive or specific by themselves: positive reaction for DNAase production, reduction of nitrate and nitrite and tributyrin hydrolysis (Catlin 1990). Furthermore, polymerase chain reaction (PCR) tests are currently considered an unequalled diagnostic assay (Greiner 2003; Post 1995; Post 1996). Modern tests show that the methods used in the present trials to identify M. catarrhalis may have introduced some misclassification in the percentage of isolates of this pathogen in participants with acute laryngitis.

By the years 1980 and 1990, the presence of B-lactamase in isolates of M. catarrhalis from the United States was 75% and 80% respectively. By 1990, B-lactamase was in over 90% of isolates from England and Scotland; and by 2003, in 87.4% of isolates from China (Fung 1991; Jorgensen 1990; Wallace 1990; Wang 2003). In a study conducted in the United States, most isolates of M. catarrhalis were resistant to amoxicillin, cefaclor, cefprozil and trimethoprim/sulfamethoxazole; among H. influenzae isolates, 28.6% were B-lactamase positive (Jacobs 2004). In the present penicillin trial, 18% of M. catarrhalis isolated at the acute visit produced B-lactamase.

 

Overall completeness and applicability of evidence

There were only two randomised controlled trials (RCTs) in this review and the data are incomplete for a number of clinically important outcomes. In addition there was no opportunity to pool data. The applicability of the evidence outside the research setting is reasonable as these studies were conducted in clinical settings that were quite similar. The comparisons in the review are commonly undertaken and not difficult to apply. The two RCTs came from the same country.

Acute laryngitis often involves rhino-pharyngolaryngitis or rhinosinubronchitis with the larynx involvement. A Cochrane review assessing the effect of antibiotics in adults with clinically diagnosed rhinosinusitis in primary care settings found that although antibiotics can shorten the time to cure (number needed to treat to benefit (NNTB) 18 (95% CI 10 to 115), significantly more participants who received antibiotics experienced adverse events (number needed to treat to harm (NNTH) 8 (95% CI 6 to 13) (Lemiengre 2012). The authors concluded there is no place for antibiotics for the patient with clinically diagnosed, uncomplicated acute rhinosinusitis.

 

Quality of the evidence

The review included two trials which were small and were judged as having moderate risk of bias. These RCTs assessed different interventions resulting in very limited opportunities to pool useful data.

 

Potential biases in the review process

We have produced updated coverage of RCTs of antibiotics for laryngitis in adults by summarising the best available evidence using quantitative methods. We have endeavoured to provide information to help clinicians and stakeholders choose the most appropriate treatment. We searched several sources to identify RCTs. However, we cannot ensure that all available RCTs were located. Although acute laryngitis is often diagnosis using clinical criteria, laryngoscopic findings are needed to have a clear diagnostic. The RCTs included in the review did not used a more specialised examination of the larynx.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

 

Implications for practice

Definitive recommendations cannot be made since evidence is only available from two randomised controlled trials (RCTs). Antibiotics appear to have no benefit in the treatment of acute laryngitis. Even if erythromycin could reduce voice disturbance at one week and cough at two weeks, measured subjectively, we consider these outcomes are not relevant in clinical practice. The implications for practice are that a prescription of antibiotics should not be given in the first instance, as they will not objectively improve symptoms. Unnecessary antibiotic prescribing may contribute to increasing rates of antibiotic resistance. Antibiotics may not outweigh their costs or adverse effects. Currently, antibiotics are widely prescribed for patients with upper respiratory tract infections (URTIs).

 
Implications for research

Although definitive recommendations cannot be made, since evidence is only available from two RCTs, it seems that there is no need for additional trials to examine antibiotics in acute laryngitis.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Liz Dooley and Sarah Thorning from the Cochrane Acute Respiratory Infections Group for their assistance. We also wish to thank the following people for commenting on the 2007 draft: Chanpen Choprapawon, Rob Ware and Abigail Fraser. Finally, we acknowledge Edgar Ospina, Carlos Granados and Johanna Osorio for their contributions in previous publications of this review.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

This review has no analyses.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Appendix 1. MEDLINE search strategy

 

MEDLINE (OVID)

1 exp Laryngitis/
2 laryngit*.tw.
3 Laryngeal diseases/
4 Laryngeal Edema/
5 laryngeal*.tw.
6 Epiglottitis/
7 epiglottit*.tw.
8 pharyngolaryngit*.tw.
9 laryngotracheit*.tw.
10 Hoarseness/
11 hoarse*.tw.
12 supraglottit*.tw.
13 Voice Disorders/
14 Voice Quality/
15 (voice adj2 (disturb* or los* or quality or disorder* or croak*)).tw.
16 or/1-15
17 exp Larynx/
18 larynx.tw.
19 exp Laryngeal Mucosa/
20 laryng*.tw.
21 Epiglottis/
22 epiglott*.tw.
23 exp Glottis/
24 glottis.tw.
25 Hypopharynx/
26 laryngopharyn*.tw.
27 hypopharyn*.tw.
28 Vocal Cords/
29 vocal cord*.tw.
30 supraglott*.tw.
31 nasopharynx.tw.
32 subglottic.tw.
33 or/17-32
34 (irritat* or sore* or infect* or inflam* or redness).tw.
35 33 and 34
36 16 or 35
37 exp Anti-Bacterial Agents/
38 antibiotic*.tw.
39 (azithromycin* or clarithromycin* or erythromycin* or roxithromycin* or macrolide*).tw.
40 (cefamandole* or cefoperazone* or cefazolin* or cefonicid* or cefsulodin* or cephacetrile* or cefotaxime* or cephalothin* or cephapirin* or cephalexin* or cephaclor* or cephadroxil* or cephaloglycin* or cephradine* or cephaloridine* or ceftazidime* or cephamycin* or cefmetazole* or cefotetan* or cefoxitin* or cephalosporin*).tw.
41 (amoxicillin* or ampicillin* or sulbactum* or tetracyclin* or clindamycin* or lincomycin* or doxycyclin*).tw.
42 (fluoroquinolone* or ciprofloxacin* or fleroxacin* or enoxacin* or norfloxacin* or ofloxacin* or pefloxacin* or moxifloxacin* or esparfloxacin* or clindamicin*).tw.
43 (penicillin* or ticarcillin* or lactam* or levofloxacin* or trimethoprim*).tw.
44 or/37-43
45 36 and 44

 

Appendix 2. EMBASE search strategy

#37. #33 AND #36
#36. #34 OR #35
#35. random*:ab,ti OR placebo*:ab,ti OR factorial*:ab,ti OR crossover*:ab,ti OR 'cross over':ab,ti OR 'cross-over':ab,ti OR volunteer*:ab,ti OR assign*:ab,ti OR allocat*:ab,ti OR ((singl* OR doubl*) NEAR/1 blind*):ab,ti
#34. 'randomized controlled trial'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp
#33. #24 AND #32
#32. #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31
#31. penicillin*:ab,ti OR ticarcillin*:ab,ti OR lactam*:ab,ti OR levofloxacin*:ab,ti OR trimethoprim*:ab,ti
#30. fluoroquinolone*:ab,ti OR ciprofloxacin*:ab,ti OR fleroxacin*:ab,ti OR enoxacin*:ab,ti OR norfloxacin*:ab,ti OR ofloxacin*:ab,ti OR pefloxacin*:ab,ti OR moxifloxacin*:ab,ti OR esparfloxacin*:ab,ti OR clindamicin*:ab,ti OR clindamycin*:ab,ti
#29. amoxicillin*:ab,ti OR amoxycillin*:ab,ti OR ampicillin*:ab,ti OR sulbactum*:ab,ti OR tetracyclin*:ab,ti OR clindamycin*:ab,ti OR lincomycin*:ab,ti OR doxycyclin*:ab,ti
#28. cefamandole*:ab,ti OR cefoperazone*:ab,ti OR cefazolin*:ab,ti OR cefonicid*:ab,ti AND cefsulodin*:ab,ti OR cephacetrile*:ab,ti OR cefotaxime*:ab,ti OR cephalothin*:ab,ti OR cephapirin*:ab,ti OR cephalexin*:ab,ti OR cephaclor*:ab,ti OR cephadroxil*:ab,ti OR cephaloglycin*:ab,ti OR cephradine*:ab,ti OR cephaloridine*:ab,ti OR ceftazidime*:ab,ti OR cephamycin*:ab,ti OR cefmetaxole*:ab,ti OR cefotetan*:ab,ti OR cefoxitin*:ab,ti OR cephalosporin*:ab,ti
#27. azithromycin*:ab,ti OR clarithromycin*:ab,ti OR erythromycin*:ab,ti OR roxithromycin*:ab,ti OR macrolide*:ab,ti
#26. antibiotic*:ab,ti
#25. 'antibiotic agent'/exp
#24. #12 OR #23
#23. #19 AND #22
#22. #20 OR #21
#21. hoarse*:ab,ti OR irritat*:ab,ti OR sore*:ab,ti OR croak*:ab,ti OR infect*:ab,ti OR inflamm*:ab,ti OR redness:ab,ti
#20. (voice NEAR/3 (loss OR lost OR disturb*)):ab,ti
#19. #13 OR #14 OR #15 OR #16 OR #17 OR #18
#18. nasopharynx:ab,ti OR subglottic:ab,ti OR supraglott*:ab,ti
#17. 'nasopharynx'/de
#16. hypopharynx:ab,ti OR laryngopharynx:ab,ti
#15. 'hypopharynx'/de
#14. larynx:ab,ti OR laryng*:ab,ti OR epiglott*:ab,ti OR glottis:ab,ti OR 'vocal cord':ab,ti OR 'vocal cords':ab,ti
#13. 'larynx'/de OR 'epiglottis'/de OR 'glottis'/exp OR 'larynx mucosa'/de OR 'vocal cord'/exp
#12. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11
#11. supraglottit*:ab,ti
#10. hoarse*:ab,ti
#9. 'hoarseness'/de
#8. pharyngolaryngit*:ab,ti OR laryngotracheit*:ab,ti
#7. epiglottit*:ab,ti
#6. 'epiglottitis'/exp
#5. laryngeal*:ab,ti
#4. 'larynx edema'/de
#3. 'larynx disorder'/de
#2. laryngit*:ab,ti
#1. 'laryngitis'/exp

 

Appendix 3. LILACS search strategy

((mh:laryngitis OR laryngit* OR laringit* OR mh:c08.360.535* OR mh:c08.730.368* OR mh:c09.400.535* OR mh:"Laryngeal Diseases" OR "Enfermedades de la Laringe" OR "Doenças da Laringe" OR laringopatias OR mh:"Laryngeal Edema" OR "Edema Laríngeo" OR laryngeal* OR mh:epiglottitis OR epiglottit* OR epiglotitis OR epiglotite OR pharyngolaryngit* OR laryngotracheit* OR mh:hoarseness OR ronquera OR rouquidão OR hoars* OR supraglottit* OR mh:"Voice Disorders" OR "Trastornos de la Voz" OR "Distúrbios da Voz" OR mh:"Voice Quality" OR "Calidad de la Voz" OR "Qualidade da Voz" OR "voice disturbance") OR ((voice OR voz) AND (disturb* OR los* OR quality OR disorder* OR croak*)) OR ((mh:larynx OR mh:a04.329* OR laringe OR larynx OR mh:"Laryngeal Mucosa" OR "Mucosa Laríngea" OR laryng* OR mh:epiglottis OR epiglotis OR epiglote OR epiglot* OR mh:glottis OR glotis OR glote OR mh:a04.329.364* OR glot* OR mh:hypopharynx OR hipofaringe OR hipofaringe OR hypopharynx OR laryngopharynx OR laringofaringe OR "vocal cords" OR "Pliegues Vocales" OR "Pregas Vocais" OR supraglot* OR nasopharynx OR subglottic) AND (infect* OR infecciones* OR infecções OR inflam* OR inflamación OR inflamação OR redness OR irritat*))) AND (mh:"Anti-Bacterial Agents" OR mh:d27.505.954.122.085* OR antibacterianos OR antibiotic* OR antibióticos OR mh:d02.540.505.250* OR mh:erythromycin OR eritromicina OR erythromycin OR mh:azithromycin OR azitromicina OR azithromycin OR clarithromycin OR claritromicina OR mh:roxithromycin OR roxithromycin OR roxitromicina OR mh:macrolides OR macrolide* OR macrólidos OR macrolídeos OR mh:cephalosporins OR cephalosporin* OR mh:d02.065.589.099.249* OR mh:d02.886.665.074* OR mh:d04.075.080.875.099.221.249* OR cefalosporin* OR cefamandole* OR cefoperazone* OR cefazolin* OR cefonicid* OR cefsulodin* OR cephacetrile* OR cefotaxime* OR cephalothin* OR cephapirin* OR cephalexin* OR cephaclor* OR cephadroxil* OR cephaloglycin* OR cephradine* OR cephaloridine* OR ceftazidime* OR cephamycin* OR cefmetazole* OR cefotetan* OR cefoxitin* OR mh:penicillins OR penicilinas OR mh:d02.065.589.099.750* OR mh:d02.886.108.750* OR mh:d03.438.260.825* OR mh:d03.605.084.737* OR mh:d04.075.080.875.099.221.750* OR penicillin* OR amoxicil* OR ampicil* OR sulbactam OR mh:tetracyclines OR tetracyclin* OR tetraciclina OR mh:clindamycin OR clindamycin OR clindamicina OR mh:lincomycin OR lincomycin OR lincomicina OR mh:doxycycline OR doxycyclin* OR doxiciclina OR mh:fluoroquinolones OR mh:d03.438.810.835.322* OR fluoroquinolon* OR ciprofloxacin* OR fleroxacin* OR enoxacin* OR norfloxacin* OR ofloxacin* OR pefloxacin* OR moxifloxacin* OR esparfloxacin* OR clindamicin* OR ticarcillin OR ticarcilina OR lactam* OR levofloxacin* OR trimethoprim* OR trimetoprim* OR mh:trimethoprim OR mh:d03.383.742.906*) AND db:("LILACS") AND type_of_study:("clinical_trials")

 

Appendix 4. Biosis Previews search strategy

 


# 45#2 AND #1

Refined by: Publication Years=( 2011 OR 2012 )

Databases=BIOSIS Previews Timespan=All Years


# 374#2 AND #1

Databases=BIOSIS Previews Timespan=All Years


# 2662,165Topic=(random* or placebo* or crossover* or "cross over" or allocat* or ((singl* or doubl*) NEAR/1 blind*)) OR Title=(trial)

Databases=BIOSIS Previews Timespan=All Years


# 11,339Topic=(laryng* or larynx* or epiglott* or glottis or laryngopharyng* or hypopharynx or "vocal cord*" or hoarse* or supraglott* or pharyngolaryng* or nasopharynx or subglottic or laryngotracheit*) AND Topic=(antibiotic* or azithromycin* or clarithromycin* or erythromycin* or roxithromycin* or macrolide* or efamandole* or cefoperazone* or cefazolin* or cefonicid* or cefsulodin* or cephacetrile* or cefotaxime* or cephalothin* or cephapirin* or cephalexin* or cephaclor* or cephadroxil* or cephaloglycin* or cephradine* or cephaloridine* or ceftazidime* or cephamycin* or cefmetazole* or cefotetan* or cefoxitin* or cephalosporin* or amoxicillin* or ampicillin* or sulbactum* or tetracyclin* or clindamycin* or lincomycin* or doxycyclin* or fluoroquinolone* or ciprofloxacin* or fleroxacin* or enoxacin* or norfloxacin* or ofloxacin* or pefloxacin* or moxifloxacin* or esparfloxacin* or clindamicin* or penicillin* or ticarcillin* or lactam* or levofloxacin* or trimethoprim*)

Databases=BIOSIS Previews Timespan=All Years



 

Appendix 5. Previous search strategies

For the 2011 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which includes the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (November 2008 to January week 3, 2011), EMBASE (November 2008 to February 2011), LILACS (November 2008 to February 2011) and BIOSIS (November 2008 to February 2011).

Prior to this we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), which includes the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (January 1966 to November Week 2 2008), EMBASE (1974 to November 2008), LILACS (from 1982 to November 2008 ) (Castro 1997) and BIOSIS (1980 to November 2008).

MEDLINE was searched using the following updated list of keywords and MeSH terms in conjunction with the highly sensitive search strategy designed by the Cochrane Collaboration for identifying RCTs. The same strategy was used to search CENTRAL and adapted to search EMBASE, LILACS and BIOSIS. See below for the original MEDLINE search strategy.

 

MEDLINE (OVID)

1 exp Laryngitis/
2 laryngit*.tw.
3 Laryngeal Edema/
4 Epiglottitis/
5 epiglottit*.tw.
6 pharyngolaryngit*.tw.
7 laryngotracheit*.tw.
8 or/1-7
9 exp Larynx/
10 larynx.tw.
11 exp Laryngeal Mucosa/
12 laryng*.tw.
13 Epiglottis/
14 epiglott*.tw.
15 exp Glottis/
16 glottis.tw.
17 Hypopharynx/
18 hypopharynx.tw.
19 laryngopharyn*.tw.
20 hypopharyn*.tw.
21 Vocal Cords/
22 vocal cord*.tw.
23 supraglott*.tw.
24 nasopharynx.tw.
25 subglottic.tw.
26 or/9-25
27 exp Voice Disorders/
28 Voice Quality/
29 (voice adj2 disturbanc*).tw.
30 hoarse*.tw.
31 infection*.tw.
32 inflammation*.tw.
33 redness.tw.
34 (los* adj3 voice).tw.
35 or/27-33
36 35 and 26
37 8 or 36
38 exp Anti-Bacterial Agents/
39 antibiotic*.tw.
40 (azithromycin* or clarithromycin* or erythromycin* or roxithromycin* or macrolide*).tw.
41 (cefamandole* or cefoperazone* or cefazolin* or cefonicid* or cefsulodin* or cephacetrile* or cefotaxime* or cephalothin* or cephapirin* or cephalexin* or cephaclor* or cephadroxil* or cephaloglycin* or cephradine* or cephaloridine* or ceftazidime* or cephamycin* or cefmetazole* or cefotetan* or cefoxitin* or cephalosporin*).tw.
42 (amoxicilline* or ampicillin* or sulbactum* or tetracycline* or clindamycin* or lincomycin* or doxycycline*).tw.
43 (floroquinolone* or ciprofloxacin* or fleroxacin* or enoxacin* or norfloxacin* or ofloxacin* or pefloxacin* or moxifloxacin* or esparfloxacin* or clindamicin*).tw.
44 (penicillin* or ticarcillin* or lactam* or levofloxacin* or trimethoprim*).tw.
45 or/38-44
46 45 and 37
47 randomized controlled trial.pt.
48 controlled clinical trial.pt.
49 randomized.ab.
50 placebo.ab.
51 drug therapy.fs.
52 randomly.ab.
53 trial.ab.
54 groups.ab.
55 47 or 48 or 49 or 50 or 51 or 52 or 53 or 54
56 (animals not (humans and animals)).sh.
57 55 not 56
58 57 and 46

 

Original MEDLINE search strategy

1 exp Laryngitis/
2 Larynx/
3 exp Laryngeal Diseases/
4 Laryngeal Edema/
5 Laryngeal Mucosa/
6 Epiglottitis/
7 Glottis/
8 Epiglottis/
9 Hypopharynx/
10 laryngopharyn*.tw.
11 Vocal Cords/
12 Hoarseness/
13 (laryngitis or larynx or laryngeal).tw.
14 (epiglottitis or epiglottis).tw.
15 (vocal adj3 cord*).tw.
16 hoarse*.tw.
17 supraglottitis.tw.
18 (pharyngolaryngitis or nasopharynx or subglottic).tw.
19 laryngotracheitis.tw.
20 or/1-19
21 exp Anti-Bacterial Agents/
22 antibiotic*.tw.
23 (azithromycin* or clarithromycin* or erythromycin* or roxithromycin* or macrolide*).tw.
24 (cefamandole* or cefoperazone* or cefazolin* or cefonicid* or cefsulodin* or cephacetrile* or cefotaxime* or cephalothin* or cephapirin* or cephalexin* or cephaclor* or cephadroxil* or cephaloglycin* or cephradine* or cephaloridine* or ceftazidime* or cephamycin* or cefmetazole* or cefotetan* or cefoxitin* or cephalosporin*).tw.
25 (amoxicilline* or ampicillin* or sulbactum* or tetracycline* or clindamycin* or lincomycin* or doxycycline*).tw.
26 (floroquinolone* or ciprofloxacin* or fleroxacin* or enoxacin* or norfloxacin* or ofloxacin* or pefloxacin* or moxifloxacin* or esparfloxacin* or clindamicin*).tw.
27 (penicillin* or ticarcillin* or lactam* or levofloxacin* or trimethoprim*).tw.
28 or/21-27
29 28 and 20
30 randomized controlled trial.pt.
31 controlled clinical trial.pt.
32 randomized.ab.
33 placebo.ab.
34 drug therapy.fs.
35 randomly.ab.
36 trial.ab.
37 groups.ab.
38 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37
39 (animals not (humans and animals)).sh.
40 38 not 39
41 40 and 29

 

Feedback

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Antibiotics for acute laryngitis in adults, 17 November 2012

 

Summary

This is a translated summary of feedback submitted in German

This review highlights the relative ineffectiveness of antibiotics in viral-induced laryngitis which is consistent with clinical experience.

Acute laryngitis requires more than a clinical diagnosis and in the absence of laryngoscopic findings, cannot be clearly diagnosed. The studies included in the review used clinical parameters for assessment. This is not an accurate diagnostic approach, since a more specialised examination of the organ is required.

Detailed examination by an ENT specialist is therefore essential for a more accurate diagnosis, in order to make a treatment decision.

In my opinion pure acute laryngitis is therefore an unusual diagnosis. In clinic, we classify it as rhino-pharyngolaryngitis or often rhinosinubronchitis with the larynx as its inevitable anatomical manifestation. The involvement of the larynx in a viral infection of the respiratory tract is clearly only part of a disease whose course is often biphasic and regularly leads to bacterial superinfection with extensions to the upper and lower respiratory tract. The corresponding culture confirms this and probably explains the better effect of erythromycin over penicillin V, which has a relatively narrow spectrum of activity. In clinical practice amoxicillin or azithromycin have become established macrolide antibiotics.

We do not know why many patients experience hoarseness primarily in the context of a common cold. Apparently there are individual areas of involvement of the respiratory system, which relate to the pathogen spectrum and to known pre-existing conditions such as allergies, asthma and chronic sinusitis. These are necessary for differential diagnosis.

Just as often, important differential diagnoses are excluded from an ENT medical examination of the vocal cord paresis (often as the primary symptom of bronchial carcinoma), incidental findings (such as vocal cord nodules), intubation granuloma or posterior laryngitis with reflux gastritis.

In contrast, in pure acute laryngitis the lupen laryngoscopic findings often appear inconspicuous, making them more characteristic of the findings and part of diagnosis. Most microscopically visible change is, depending on the stage of the disease, streaky redness and visible blood vessels in the vocal cords. Monochorditis associated with tuberculosis can also be determined.

ENT examination including nasal and laryngeal endoscopy enables more targeted treatment decisions, with the aim of avoiding unnecessary antibiotic therapy. This is not a frequent outcome, since prognostic assessment of the disease process includes age, immune status, smoking, co-morbidities such as OSA and COPD, and relative dryness of mouth especially with concomitant antihypertensives or pre-existing laryngeal diseases.

Due to the protracted nature of this condition, patients may expect additional antibiotic therapy. However, achieving effective treatment with systemic application is hampered by the poor blood supply to the vocal cords.

The most important therapy in acute laryngitis is total voice rest. This is difficult for people who undertake work which requires them to talk. Humidification of the respiratory tract by inhalation, supplemented with mucolytics, sage and thyme, can reduce inflammation of the larynx caused by the surrounding laryngeal mucosa and can alleviate symptoms. Consideration of concomitant risk factors should be flagged up as part of the investigation and taken into consideration along with other indications for treatment.

There is a lack of data showing the extent to which early treatment with antibiotic therapy can prevent pneumonia in the elderly.

Since reviews published in the Cochrane Library are gaining acceptance as part of evidence-based medicine which serves as a basis for further patient care, there should also be a general statement on the necessary differential diagnosis. Hoarseness as a symptom is not the sole criterion for the assessment of a disease. The task of good clinical practice may be to provide treatment protocols which take account of individual factors and which apply a more evidence-based approach to the treatment of disease. To this end, the Cochrane Library provides a good basis for discussion.

The original feedback comment

Der Artikel Antibiotics for acute laryngitis in adults unterstreicht die relative Wirkungslosigkeit von Antibiotika bei einer viral ausgelösten Laryngitis. Dies entspricht der klinischen Erfahrung.

Die akute Laryngitis ist mehr als eine klinische Diagnose. Ohne laryngoskopischen Befund kann diese Diagnose nicht eindeutig gestellt werden. Die zugrundegelegten Studien enthalten hierüber keine Aussagen, da sie nicht mehr als klinische Parameter zur Einschätzung nutzen. Dies wird der Diagnose nicht gerecht, die als solche nur fachärztlich nach Untersuchung des Organs gestellt werden kann.

Die eingehende HNO-ärztliche Untersuchung ist zur feineren Diagnose deshalb unentbehrlich, gerade um eine Therapieentscheidung vorzunehmen.

Eine reine akute Laryngitis ist daher eher m.E. eine absolute Ausnahmediagnose. In der Klinik stufen wir sie als Rhinopharyngolaryngitis oder oft zwangsläufige Beteiligung des Kehlkopfes als anatomische Schnittstelle einer Rhinosinubronchitis ein. Hierdurch wird deutlich, dass die Beteiligung des Kehlkopfes bei einer viralen Infektion der Atemwege nur Teil eines Krankheitsbildes ist, deren Verlauf häufig biphasisch ist und es im weiteren regelmäßig zu einer bakteriellen Superinfektion mit einer Ausweitung auf die oberen und unteren Atemwege kommt. Die entsprechenden Keimnachweise belegen diesen Aspekt und führen zu der auch nachvollziehbaren besseren Wirkung von Erythromycin  als Penicillin V, das ein relativ enges Wirkspektrum besitzt. In der klinischen Praxis hat sich eher Amoxicillin oder Azithromycin als Makrolidantibiotikum durchgesetzt.

Wir wissen nicht, warum viele Patienten primär im Rahmen einer common cold mit einer Heiserkeit reagieren. Anscheinend gibt es im Atemwegssystem individuelle Prädilektionsstellen, die abhängig sind von dem Erregerspektrum, bekannten Vorerkrankungen wie Allergien, Asthma und chronischen Sinusitiden.  Diese gehören zur notwendigen Differenzialdiagnostik.

Ebenso werden häufig wichtige Differenzialdiagnosen bei einer HNO-ärztlichen Untersuchung ausgeschlossen etwa die Stimmbandparese ( nicht selten als primäres Symptom eines Bronchialkarzinomes), Zufallsbefunde wie Stimmbandknötchen, Intubatonsgranulome oder eine Laryngitis posterior bei einer Refluxgastritis.

Dagegen erscheint der lupenlaryngoskopische Befund bei einer rein akuten Laryngitis zumeist unauffällig und ist damit eher charakteristischer Befund und Teil der Diagnosestellung. Häufigste mikroskopisch sichtbare Veränderung abhängig vom Krankheitsstadium ist eine streifige Rötung und Gefäßinjektion der Stimmbänder. Hinzuweisen ist auch auf eine Monochorditis bei einer Tuberkulose.

Die HNO-ärztliche Untersuchung einschließlich der Endoskopie der Nase und des Kehlkopfes führt durch die Zusammenschau der Befunde auf die Fährte und ermöglicht eine zielgerichtetere Therapieentscheidung, die primär die Vermeidung unnötiger Antibiotikatherapien zum Ziel hat, oft aber ohne diese nicht auskommt, da die prognostische Einschätzung des Krankheitsverlaufes das Alter, den Immunstatus, Nikotinabusus, Begleiterkrankungen wie OSAS und COPD, relative Mundtrockenheit vor allem durch gleichzeitige Einnahme von Antihypertensiva oder vorbestehende Kehlkopferkrankungen mit einschließt. 

Erwartungshaltungen während der zwar selbstlimitierenden, aber doch bis zu 14 Tagen und mehr relativ protrahiert verlaufenden Erkrankung wecken dabei bei den Patienten den Wunsch nach einer zusätzlichen Antibiotikatherapie. Dabei werden entsprechende Wirkspiegel systemischer Applikationen aufgrund der eher spärlichen Durchblutung der Stimmbänder schwer erreicht.

Wichtigste Therapie ist bei der akuten Laryngitis die absolute Stimmruhe gerade in Sprechberufen und die Befeuchtung der Atemwege durch Inhalationen, die durch Mukolytika, Salbei und Thymian ergänzt werden kann und zu einer Beruhigung der den Kehlkopf umgebenden Schleimhaut führt und als symptomatische Behandlung die subjektiven Beschwerden lindert.  Nach begleitenden Risikofaktoren sollte daher bei eingehender Untersuchung gefahndet und diese mit in die Überlegungen bei der Indikation einer Therapie mit einbezogen werden.

Es fehlen darüber hinaus Daten, die belegen, inwieweit eine frühzeitig einsetzende Antibiotikatherapie beispielsweise gerade bei älteren Patienten eine Pneumonie abwenden kann.

Da die vorliegenden Ergebnisse der Cochrane Library auch zunehmend Eingang finden in die evidenzbasierte Medizin, die als Grundlage für die weitere Patientenversorgung dient, sollten hier vor einer generellen Aussage die erforderlichen differenzialdiagnostischen Überlegungen Eingang finden. Heiserkeit als Symptom ist kein alleiniges Kriterium für die Beurteilung einer Erkrankung. Aufgabe der guten klinischen Praxis kann es werden, die Patienten im Rahmen von Behandlungsprotokollen im Hinblick auf die notwendige Betrachtung der einzelnen Begleitfaktoren zu begleiten und hierüber mehr notwendige Aussagen im Hinblick auf die verbesserte evidenzbasierte Behandlung von Erkrankungen treffen zu können. Hierzu bietet die Cochrane Library eine gute Diskussionsgrundlage.

Dr. Hans Christoph Reeker,
ENT Specialist

I agree with the conflict of interest statement below:
I certify that I have no affiliations with or involvement in any organization or entity with a financial interest in the subject matter of my feedback.

 

Reply

Thank you for your feedback on the Cochrane review Antibiotics for acute laryngitis in adults. We have updated the review and addressed your comments regarding the problems of a precise diagnosis for acute laryngitis.

 

Contributors

Feedback comment kindly translated by Toby Lasserson and checked by Dr. Hans Christoph Reeker.
Feedback reply by Ludovic Reveiz and Andres Cardona.

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Last assessed as up-to-date: 30 January 2013.


DateEventDescription

27 February 2013Feedback has been incorporatedFeedback and reply included in this update.

30 January 2013New citation required but conclusions have not changedOur conclusions remain unchanged.

30 January 2013New search has been performedSearches updated. There were no new included or excluded trials to add to the review.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Protocol first published: Issue 2, 2004
Review first published: Issue 1, 2005


DateEventDescription

6 October 2010AmendedContact details updated.

21 January 2010AmendedContact details updated.

8 May 2009AmendedContact details updated.

22 November 2008New search has been performedConverted to new review format.

19 November 2008New search has been performedWe updated the searches in November 2008. There were no new included or excluded trials to add to the review.

17 December 2006New search has been performedWe updated the searches in December 2006. There were no new included or excluded trials to add to the review.

23 June 2004New search has been performedSearches conducted.



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

Ludovic Reveiz (LR), Andrés Cardona (AC) and Edgar Ospina (EO) initiated, designed and conducted the study.
Ludovic Reveiz and Andrés Cardona provided methodological perspectives and techniques for writing the protocol and the review.

An update was performed in December 2006. Ludovic Reveiz and Andrés Cardona evaluated the titles and abstracts of the search. All the review authors contributed to manuscript revision.

An update was performed in November 2008. Ludovic Reveiz and Andrés Cardona evaluated the titles and abstracts of the search. All the review authors contributed to manuscript revision.

An update was performed in January 2013. Ludovic Reveiz and Andrés Cardona evaluated the titles and abstracts of the search. Both the review authors (LR, AC) contributed to manuscript revision.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. Feedback
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Index terms
 

Internal sources

  • None, Not specified.

 

External sources

  • None, Not specified.

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Schalén 1985 {published data only}
  • Schalén L, Christensen P, Eliasson I, Fex S, Kamme C, Schalen C. Inefficacy of penicillin V in acute laryngitis in adults. Evaluation from results of double-blind study. Annals of Otology, Rhinology, and Laryngology 1985;94(1 Pt 1):14-7.
Schalén 1993 {published data only}
  • Schalén L, Eliasson I, Kamme C, Schalen C. Erythromycin in acute laryngitis in adults. Annals of Otology, Rhinology, and Laryngology 1993;102(3 Pt 1):209-14.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
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References to other published versions of this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. Feedback
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Characteristics of studies
  19. References to studies included in this review
  20. References to studies excluded from this review
  21. Additional references
  22. References to other published versions of this review
Reveiz 2005
Reveiz 2007
Reveiz 2009
Reveiz 2011
  • Reveiz L, Cardona AF, Ospina EG. Antibiotics for acute laryngitis in adults. Cochrane Database of Systematic Reviews 2011, Issue 5. [DOI: 10.1002/14651858.CD004783.pub3]