Postantibiotic and sub-MIC effects of benzylpenicillin against Streptococcus pneumoniae with different susceptibilities for penicillin

BACKGROUND: The purpose of the study was to examine whether penicillin-susceptible and nonsusceptible strains of Streptococcus pneumoniae exhibited different pharmacodynamic responses to benzylpenicillin. METHODS: The postantibiotic effects (PAEs) and the postantibiotic sub-MIC effects (PA SMEs) were investigated by optical density against strains of S. pneumoniae with different susceptibilities to benzylpenicillin. To validate the data, the PAE and PA SME of one susceptible and one resistant strain were also tested with the viable count method. The post-MIC effects (PMEs) were studied in an in vitro kinetic model, simulating human pharmacokinetics with a half-life of 1 h and a time above MIC of approximately 20% of 24 h. RESULTS: There were no differences with respect to the PAEs, PA SMEs and PMEs of benzylpenicillin for the various strains of S. pneumoniae, irrespective of their susceptibility to penicillin. For both some of the susceptible and resistant strains investigated, longer PA SMEs at 0.2 and 0.3 x MIC were noted, indicating that these parameters might be more dependent on the type of strain rather than on the susceptibility status. CONCLUSION: No differences in the pharmacodynamic response after similar drug exposure were seen for S. pneumoniae strains with different penicillin susceptibility.