Pharmacokinetic-pharmacodynamic modeling of meropenem against VIM producing Klebsiella pneumoniae isolates: Clinical implications.

Pharmacokinetic-pharmacodynamic modeling of meropenem against VIM producing Klebsiella pneumoniae isolates: Clinical implications. J Med Microbiol. 2015 Dec 23; Authors: Tsala M, Vourli S, Kotsakis S, Daikos G, Tzouvelekis L, Zerva L, Miriagou V, Meletiadis J Abstract VIM producing Klebsiella pneumoniae isolates are usually associated with high MICs to carbapenems. Preclinical studies investigating the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of carbapenems against these isolates are lacking. The in vitro antibacterial activity of meropenem against one wild-type and three VIM producing K. pneumoniae clinical isolates (median MICs 0.031, 8, 16 and 128 mg/L) was studied in a dialysis-diffusion PK-PD model and verified in a thigh infection neutropenic animal model by testing selected strains and exposures. The in vitro PK-PD target associated with bactericidal activity was estimated and the target attainment for different dosing regimens was calculated with Monte Carlo analysis. The in vitro model was correlated with the in vivo data with CFU reduction of <1log10 for the VIM-producing (MIC=16 mg/L) and >2log10 the wild-type isolate (MIC=0.031 mg/L) isolate with fT>MIC 25% and 100%, respectively. The in vitro bactericidal activity for all isolates was associated with a 40% fT>MIC and attained in >90% of cases with the standard 1g q8 0.5h infusion dosing regimen only for isolates with MICs up to 1 mg/L. For i...
Source: Journal of Medical Microbiology - Category: Microbiology Authors: Tags: J Med Microbiol Source Type: research