Systematic review of factors contributing to penicillin treatment failure in Streptococcus pyogenes pharyngitis

Review the evidence for various explanations for microbiologic treatment failure following use of penicillin in group A streptococcal (GAS) tonsillopharyngitis.

Systematic review of the literature based on Medline and EMBASE searches, and review of reference lists of included studies.

The explanations for penicillin treatment failure in GAS tonsillopharyngitis include 1) carrier state, 2) lack of compliance, 3) recurrent exposure, 4) in vivo copathogenicity of beta-lactamase-producing normal pharyngeal flora, 5) in vivo bacterial coaggregation, 6) poor antibiotic penetration to tonsillopharyngeal tissue, 7) in vivo eradication of normal protective flora, 8) early initiation of antibiotic therapy resulting in suppression of an adequate host immune response, 9) intracellular localization of GAS, 10) GAS tolerance to penicillin, 11) contaminated toothbrushes or orthodontic appliances, and 12) transmission from the family pet. There is very little type I or II evidence to support any of the above-cited explanations for treatment failure in GAS tonsillopharyngitis; available studies are mostly observational (in patients) or laboratory-based without clinical confirmation.

Multiple explanations have been offered by investigators to explain penicillin treatment failures in GAS tonsillopharyngitis, but the evidence base to support the proposed explanations is generally weak by current standards. Further research is needed to better understand the mechanism(s) of penicillin treatment failure in GAS tonsillopharyngitis.