A Cochrane review assessed the effects of penicillin compared to placebo and the effects of different penicillin regimens and formulations for preventing streptococcal infection and rheumatic fever recurrence. Nine studies were included (n=3 008). Three trials (n=1 301) compared penicillin with control. Only one of three studies showed that penicillin reduced rheumatic fever recurrence (RR 0.45, 95% CI 0.22 to 0.92) and streptococcal throat infection (RR 0.84, 95% CI 0.72 to 0.97). Four trials (n=1 098) compared intramuscular with oral penicillin and all showed that intramuscular penicillin reduced rheumatic fever recurrence and streptococcal throat infections compared to oral penicillin. One trial (n=360) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every two weeks was better at reducing rheumatic fever recurrence (RR 0.52, 95% CI 0.33 to 0.83) and streptococcal throat infections (RR 0.60, 95% CI 0.42 to 0.85). One trial (n=249) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI 0.48 to 0.92) compared to 4-weekly intramuscular penicillin.
Comment: The quality of evidence is downgraded by poor study quality and by inconsistency (variability in results across studies).