Different antibiotics for group A streptococcal pharyngitis

Review question

We wanted to know which antibiotic was more effective in treating sore throats caused by bacteria (group A beta-haemolytic streptococci (GABHS)).

Background

Most sore throats are caused by viruses, but many people carry throat bacteria, sometimes causing bacterial throat infection.

GABHS infection can have serious complications including rheumatic fever and kidney disease. Antibiotics are often prescribed to prevent complications, but provide modest benefit for sore throat, even if GABHS are present. Most throat infections are self-limiting and complication risks is extremely low for most people in high-income countries. However, sometimes antibiotics are needed. Penicillin, a cheap antibiotic, has been used to treat GABHS for many years. GABHS resistance to penicillin is rare.

Search date

We searched the literature to March 2016.

Study characteristics

We included 19 trials (18 publications) that involved 5835 people. Trials studied different antibiotics for people with sore throat who tested positive for GABHS, and were aged from one month to 80 years. Nine trials included only children; and nine included people aged 12 years or older. Most studies were published over 15 years ago; all but one reported on clinical outcomes.

Study funding sources

Thirteen trials were supported by drug study funding - some received grants - others included people employed by drug companies. Five studies did not report funding.

Key results

Antibiotic effects were similar, and all caused side effects (such as nausea and vomiting, rash), but there was no strong evidence to show meaningful differences between antibiotics. 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.

All studies were in high-income countries with low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities where risk remains high. Our review supports the use of penicillin as a first choice antibiotic in patients with throat infections caused by GABHS.

Quality of the evidence

Evidence quality was low or very low for all outcomes when macrolides or cephalosporins were compared with penicillin. Evidence quality was downgraded because of concerns about randomisation and blinding, wide confidence intervals (estimates were not very precise) and statistical differences among studies that may impact on the validity of the estimate. Most study authors did not report enough information about methods to be sure there was no bias.

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.

Read the full 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 strategy: 

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.

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