Different antibiotics for group A streptococcal pharyngitis

Which antibiotic is better for pharyngitis (or sore throat)?

Key messages
The effect on the resolution of symptoms of sore throat/pharyngitis caused by group A beta-haemolytic streptococci (GABHS) was similar between different antibiotics. All antibiotics may cause adverse effects.

What is pharyngitis?
Pharyngitis (or sore throat) is an inflammation of the throat that is caused by viruses or bacteria (e.g. group A beta-haemolytic streptococci). It usually resolves without treatment. The risk of complications is extremely low for most people in high-income countries. However, GABHS infection can have serious complications in some populations.

How is pharyngitis treated?
Sometimes antibiotics are prescribed. Penicillin has been used to treat GABHS for many years. GABHS resistance to penicillin is rare. However, antibiotics provide only modest benefits, even if GABHS is present.

What did we want to find out?
We wanted to find out which antibiotic was more effective in treating sore throats caused by GABHS.

What did we do?
We searched for randomised, double-blinded, controlled trials that compared different antibiotics for people with sore throat who tested positive for GABHS, and were aged from one month to 80 years.

What did we find?
We included 19 trials (18 publications) that involved 5839 people. 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 to patients.

Main results
We found that the effects of the different antibiotics (such as penicillin, cephalosporins, macrolides, azithromycin, and carbacephem) on symptom improvement were similar. All antibiotics caused adverse effects (such as nausea and vomiting, diarrhoea, rash). Studies did not report on long-term complications. Therefore, it was unclear if any class of antibiotics was better at preventing serious but rare complications. The incidence of penicillin allergy was poorly reported in the included trials. Our findings suggest that in the context of preserving antibiotics, penicillin remains a useful antibiotic if treatment of GABHS pharyngitis with antibiotics is needed.

What are the limitations of the evidence?
We have little or very little confidence in the evidence because the study methods were poorly reported, and we have concerns about the fact that the effect estimates were not precise and there were many differences between the pooled studies.

All studies were performed in high-income countries where the risk of streptococcal complications is low, so there is a need for trials in low-income settings and disadvantaged populations, where the risk of complications remains high.

How up-to-date is this evidence?
The evidence is current to 19 March 2023.

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. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. 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 disadvantaged populations, where the risk of complications remains high.

Read the full abstract...

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 2021.


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 Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.

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 recommended by Cochrane. We assessed the risk of bias in the 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 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). Based on an analysis of evaluable participants, 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). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant.

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 at preventing serious but rare complications.