Impact of Inoculum Size and Heterogeneous Vancomycin-Intermediate Staphylococcus aureus (hVISA) on Vancomycin Activity and Emergence of VISA in an In Vitro Pharmacodynamic Model

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Abstract
The activity of vancomycin against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and non-hVISA isolates, using an in vitro pharmacodynamic model, was reduced in the presence of a high inoculum amount (10 8 CFU/ml). A high bacterial load of >10 5 CFU/ml persisted for all strains with doses up to 5 g every 12 h against high inoculum amounts. No change in the vancomycin MIC was detected in any isolate at a moderate inoculum amount (10 6 CFU/ml), and bactericidal activity occurred only against the non-hVISA isolate (time to 99% kill, 7.5 h; P = 0.001).