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, which sometimes causes 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 resolve without treatment, and complication risks are extremely low for most people in high-income countries. However, sometimes antibiotics are needed. Penicillin, an inexpensive antibiotic, has been used to treat GABHS for many years. GABHS resistance to penicillin is rare.

Search date

We searched the literature to 3 September 2020.

Study characteristics

We included 19 trials (18 publications) that involved 5839 people. The included 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 10 trials included people aged 12 years or older. Most studies were published over 15 years ago, and all but one reported on outcome measures relevant for patients.

Study funding sources

Twelve trials reported funding from drug companies. Authors of six trials (in five publications) were employed by drug companies. Seven trials (in six publications) did not report funding sources.

Key results

Antibiotic effects were similar, and all antibiotics 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, therefore it was unclear if any class of antibiotics was better in preventing serious but rare complications.

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

Certainty of the evidence

We judged the certainty of the evidence as low or very low for all outcomes when macrolides or cephalosporins were compared with penicillin. We have concerns about the rigour of the study methods, the fact that estimates were not very precise and about the differences between studies.

Authors' conclusions: 

We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.

Read the full abstract...
Background: 

Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020.

Objectives: 

To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); 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 the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020.

Selection criteria: 

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

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 the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.

Main results: 

We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals.

Cephalosporins versus penicillin

We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events.

Macrolides versus penicillin

We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence). 

Azithromycin versus amoxicillin

Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence).

Carbacephem versus penicillin

There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants).

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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