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Review
. 2016 Sep 11;9(9):CD004406.
doi: 10.1002/14651858.CD004406.pub4.

Different antibiotic treatments for group A streptococcal pharyngitis

Mieke L van Driel  1 , An Im De Sutter, Hilde Habraken, Sarah Thorning, Thierry Christiaens
Affiliations
Review

Different antibiotic treatments for group A streptococcal pharyngitis

Mieke L van Driel et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Antibiotics provide only modest benefit in treating sore throat, although effectiveness increases in participants with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated.

Objectives: To assess the evidence on the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing relapse; and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.

Search methods: We searched CENTRAL (2016, Issue 3), MEDLINE Ovid (1946 to March week 3, 2016), Embase Elsevier (1974 to March 2016), and Web of Science Thomson Reuters (2010 to March 2016). We also searched clinical trials registers.

Selection criteria: Randomised, double-blind trials comparing different antibiotics and reporting at least one of the following: clinical cure, clinical relapse, or complications or adverse events, or both.

Data collection and analysis: Two review authors independently screened trials for inclusion, and extracted data using standard methodological procedures as recommended by Cochrane. We assessed risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions and used the GRADE tool to assess the overall quality of evidence for the outcomes.

Main results: We included 19 trials (5839 randomised participants); seven compared penicillin with cephalosporins, six compared penicillin with macrolides, three compared penicillin with carbacephem, one trial compared penicillin with sulphonamides, one trial compared clindamycin with ampicillin, and one trial compared azithromycin with amoxicillin in children. All included trials reported clinical outcomes. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. The overall quality of the evidence assessed using the GRADE tool was low for the outcome 'resolution of symptoms' in the intention-to-treat (ITT) analysis and very low for the outcomes 'resolution of symptoms' of evaluable participants and for adverse events. We downgraded the quality of evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals (CIs).There was a difference in symptom resolution in favour of cephalosporins compared with penicillin (evaluable patients analysis odds ratio (OR) for absence of resolution of symptoms 0.51, 95% CI 0.27 to 0.97; number needed to treat to benefit (NNTB) 20, N = 5, n = 1660; very low quality evidence). However, this was not statistically significant in the ITT analysis (OR 0.79, 95% CI 0.55 to 1.12; N = 5, n = 2018; low quality evidence). Clinical relapse was lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; NNTB 50, N = 4, n = 1386; low quality evidence), but this was found only in adults (OR 0.42, 95% CI 0.20 to 0.88; NNTB 33, N = 2, n = 770). There were no differences between macrolides and penicillin for any of the outcomes. One unpublished trial in children found a better cure rate for azithromycin in a single dose compared to amoxicillin for 10 days (OR 0.29, 95% CI 0.11 to 0.73; NNTB 18, N = 1, n = 482), but there was no difference between the groups in ITT analysis (OR 0.76, 95% CI 0.55 to 1.05; N = 1, n = 673) or at long-term follow-up (evaluable patients analysis OR 0.88, 95% CI 0.43 to 1.82; N = 1, n = 422). Children experienced more adverse events with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; N = 1, n = 673). Compared with penicillin carbacephem showed better symptom resolution post-treatment in adults and children combined (ITT analysis OR 0.70, 95% CI 0.49 to 0.99; NNTB 14, N = 3, n = 795), and in the subgroup analysis of children (OR 0.57, 95% CI 0.33 to 0.99; NNTB 8, N = 1, n = 233), but not in the subgroup analysis of adults (OR 0.75, 95% CI 0.46 to 1.22, N = 2, n = 562). Children experienced more adverse events with macrolides compared with penicillin (OR 2.33, 95% CI 1.06 to 5.15; N = 1, n = 489). Studies did not report on long-term complications so it was unclear if any class of antibiotics was better in preventing serious but rare complications.

Authors' conclusions: There were no clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Limited evidence in adults suggests cephalosporins are more effective than penicillin for relapse, but the NNTB is high. Limited evidence in children suggests carbacephem is more effective than penicillin for symptom resolution. Data on complications are too scarce to draw conclusions. Based on these results and considering the low cost and absence of resistance, penicillin can still be regarded as a first choice treatment for both adults and children. All studies were in high-income countries with low risk of streptococcal complications, so there is need for trials in low-income countries and Aboriginal communities where risk of complications remains high.

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Conflict of interest statement

Mieke L van Driel: None known. An IM De Sutter: None known. Hilde Habraken: None known. Sarah Thorning: None known. Thierry Christiaens: None known

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 1 Resolution of symptoms post‐treatment (ITT analysis).
1.2
1.2. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 2 Resolution of symptoms post‐treatment (evaluable participants).
1.3
1.3. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 3 Resolution of symptoms within 24 hours of treatment (ITT analysis).
1.4
1.4. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 4 Sore throat (ITT analysis).
1.5
1.5. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 5 Fever (ITT analysis).
1.6
1.6. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 6 Incidence of relapse (evaluable participants).
1.7
1.7. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 7 Complications (ITT analysis).
1.8
1.8. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 8 Adverse events (ITT analysis).
1.9
1.9. Analysis
Comparison 1 Cephalosporin versus penicillin, Outcome 9 Resolution of symptoms ITT (subgroup sponsored versus no sponsor reported).
2.1
2.1. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 1 Resolution of symptoms post‐treatment (ITT analysis).
2.2
2.2. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 2 Resolution of symptoms post‐treatment (evaluable participants only).
2.3
2.3. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 3 Sore throat post‐treatment (ITT analysis).
2.4
2.4. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 4 Fever post‐treatment (ITT analysis).
2.5
2.5. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 5 Incidence of relapse (evaluable participants).
2.6
2.6. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 6 Adverse events (ITT analysis).
2.7
2.7. Analysis
Comparison 2 Macrolide versus penicillin, Outcome 7 Resolution of symptoms ITT (subgroup sponsored versus no sponsor reported).
3.1
3.1. Analysis
Comparison 3 Azithromycin versus amoxicillin, Outcome 1 Clinical cure at 24‐28 days (ITT).
3.2
3.2. Analysis
Comparison 3 Azithromycin versus amoxicillin, Outcome 2 Clinical cure at 24‐28 days (bacteriological per protocol population).
3.3
3.3. Analysis
Comparison 3 Azithromycin versus amoxicillin, Outcome 3 Relapse on day 38‐45 (ITT).
3.4
3.4. Analysis
Comparison 3 Azithromycin versus amoxicillin, Outcome 4 Relapse on day 38‐45 (bacteriological per protocol).
3.5
3.5. Analysis
Comparison 3 Azithromycin versus amoxicillin, Outcome 5 Adverse events (all patients).
4.1
4.1. Analysis
Comparison 4 Carbacephem versus penicillin, Outcome 1 Resolution of symptoms post‐treatment (ITT analysis).
4.2
4.2. Analysis
Comparison 4 Carbacephem versus penicillin, Outcome 2 Resolution of symptoms post‐treatment (evaluable participants).
4.3
4.3. Analysis
Comparison 4 Carbacephem versus penicillin, Outcome 3 Incidence of relapse (evaluable participants).
4.4
4.4. Analysis
Comparison 4 Carbacephem versus penicillin, Outcome 4 Adverse events (ITT analysis).
5.1
5.1. Analysis
Comparison 5 Clindamycin versus ampicillin, Outcome 1 Adverse events (ITT analysis).
6.1
6.1. Analysis
Comparison 6 Sulfonamide versus penicillin, Outcome 1 Adverse events (ITT analysis).
See this image and copyright information in PMC

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References to other published versions of this review

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