Synergistic Activity of Colistin/Fosfomycin Combination against Carbapenemase-Producing Klebsiella pneumoniae in an In Vitro Pharmacokinetic/Pharmacodynamic Model

BioMed Research International
Jin WangYun Cai

Abstract

Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the greatest threats to public health, and combination therapy may be the chemotherapeutic option. In the present study, we aimed to evaluate the antibacterial effects of colistin/fosfomycin combination against carbapenemase-producing K. pneumoniae. The antibacterial effects were determined in a one-compartment in vitro pharmacokinetic model over a period of 24 h. The initial inoculum was 108 CFU/mL. Low, medium, and high Cmax values of colistin at 0.5, 2, and 5 mg/L as well as Cmax of fosfomycin at 100 mg/L were simulated in the model. Doses of both colistin and fosfomycin were given every 8 h until 24 h. For the colistin- and fosfomycin-susceptible isolate KP47, three combination regimens showed greater killing effect compared with colistin monotherapy. The greatest killing effect was observed in combination regimen containing 5 mg/L colistin. For colistin-heteroresistant and fosfomycin-susceptible isolate KP79, combination regimen containing low dose colistin (0.5 mg/L) showed no synergistic or additive effects. However, combination regimens containing 2 and 5 mg/L colistin maintained the bactericidal effect until 24 h compared with colistin monot...Continue Reading

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Methods Mentioned

BETA
PCR
genotyping

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