Penicillin tolerance and treatment failure in group A streptococcal pharyngotonsillitis

Failure of treatment of group A streptococcal pharyngitis and tonsillitis is well documented. One of the possible explanations for treatment failure is penicillin tolerance in group A streptococci. Reports on the prevalence of penicillin tolerance among group A streptococci (0-100%) and the presumed relationship with therapeutic failure vary considerably. Therefore, it appears worthwhile to review pharyngotonsillitis studies, devoting special attention to the variables of MIC-MBC laboratory determinations such as inoculum preparation, composition and volume of test medium, and the criteria used to define penicillin tolerance. Alternative methods (gradient-replica plate method, beta-lactamase disk test, time-kill assay, and cell-lysis assay) are discussed. It is concluded that technical factors and the definitions used influenced the reported rates of penicillin tolerance. The epidemiological data suggest that tolerance is not limited to a single streptococcal serotype. Furthermore, there is not sufficient data to support a correlation between in vitro penicillin tolerance of group A streptococci and treatment failure, either in clinical cases or in animal studies. On the other hand, evidence to exclude penicillin tolerance as a cause of treatment failure is also not available. Therefore, at present penicillin tolerance cannot be ruled out as a cause of penicillin treatment failures.