Effects of benzylpenicillin on Streptococcus pyogenes during the postantibiotic phase in vitro

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Abstract
A postantibiotic effect (PAE) for Streptococcus pyogenes Ml2, PI800 was induced by 10 × MIC of benzylpenicillin for 2 h in vitro. The PAE was found to be 2·4 h (range 1·75–3.0 h). No incorporation of 3H-thymidine by the streptococci occurred during the first hours of the postantibiotic phase (PA-phase), indicating that bacterial cell division was inhibited during this period. However, these bacteria showed the same killing rate as previously unexposed control cultures when 10 × MIC of benzylpenicillin was added during the PA-phase. When bacteria in PA-phase were re-exposed to penicillin at a concentration of 0·2 × MIC multiplication of the bacteria was inhibited for 6–7 h, while at a concentration of 0·3 × MIC slow killing was induced. In contrast, previously untreated controls exposed to 0·2 × MIC and 0·3 × MIC showed a growth rate corresponding to that of bacteria grown in the absence of penicillin. The effects of subinhibitory concentrations on streptococci previously exposed to penicillin may therefore be a more important factor in determining dosage intervals than the PAE.