Pharmacodynamics of colistin resistance in carbapenemase-producing Klebsiella pneumoniae: the double-edged sword of heteroresistance and adaptive resistance (original) (raw)

Journal of Medical Microbiology

Abstract

Introduction. The presence of heteroresistant subpopulations and the development of resistance during drug exposure (adaptive resistance) limits colistin’s efficacy against carbapenemase-producing Klebsiella pneumoniae (CP-Kp) isolates. Hypothesis/Gap statement. The pharmacokinetic/pharmacodynamic (PK/PD) characteristics of both types of colistin resistance against CP-Kp are unknown. Aim. We therefore studied the PK/PD characteristics of colistin resistance in an in vitro PK/PD model simulating clinical colistin exposures. Methods. Two K. pneumoniae clinical isolates, one non-CP-Kp and one CP-Kp, with colistin MICs of 0.5–1 mg l−1 at a final inoculum of 107 c.f.u. ml−1 were used in an in vitro PK/PD dialysis/diffusion closed model simulating 4.5 MU q12h and 3 MU q8h clinical dosing regimens. Heteroresistant (HRS, bacteria with stable high-level resistance present before drug exposure) and adaptive resistant (ARS, bacteria with reversible low-level resistance emerging after drug expo...

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