Intramuscular penicillin is more effective than oral penicillin in secondary prevention of rheumatic fever--a systematic review

S Afr Med J. 2003 Mar;93(3):212-8.


Background: People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin.

Objectives: To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence.

Search strategy: We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field.

Selection criteria: Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF.

Data collection and analysis: Two reviewers independently assessed trial quality and extracted data.

Main results: Six studies were included (1,707 patients). Data were not pooled because of clinical and methodological heterogeneity of the trials. Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin. One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85). One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin.

Conclusions: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor-quality trials and the use of outdated formulations of oral penicillin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Humans
  • Injections, Intramuscular
  • Penicillins / administration & dosage*
  • Penicillins / therapeutic use*
  • Rheumatic Fever / etiology
  • Rheumatic Fever / prevention & control*
  • Streptococcal Infections / complications
  • Streptococcal Infections / drug therapy*


  • Penicillins