In vitro pharmacodynamic properties of colistin and colistin methanesulfonate against Pseudomonas aeruginosa isolates from patients with cystic fibrosis

The in vitro pharmacodynamic properties of colistin and colistin methanesul fonate were investigated by studying the MICs, time-kill kinetics, and post antibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis, Twenty-three clini cal strains, including multiresistant strains, and one type strain were sel ected for MIC determination. Eleven strains were resistant; MICs for these strains were > 128 mg/liter, For the susceptible strains, MICs of colistin ranged from 1 to 4 mg/liter, while the MICs of colistin methanesulfonate we re significantly higher and ranged from 4 to 16 mg/liter, The time-kill kin etics were investigated with three strains at drug concentrations ranging f rom 0.5 to 64 times the MIC. Colistin showed extremely rapid killing, resul ting in complete elimination at the highest concentrations within 5 min, wh ile colistin methanesulfonate killed more slowly, requiring a concentration of 16 times the MIC to achieve complete killing within 24 h, Colistin exhi bited a significant PAE of 2 to 3 h at 16 times the MIC against the three s trains after 15 min of exposure. For colistin methanesulfonate, PAEs were s horter at the concentrations tested. Colistin methanesulfonate had lower ov erall bactericidal and postantibiotic activities than colistin, even when a djusted for differences in MICs, Our data suggest that doses of colistin me thanesulfonate higher than the recommended 2 to 3 mg/kg of body weight ever y 12 h may be required for the effective treatment of P. aeruginosa infecti ons in cystic fibrosis patients.