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Antimicrobial Agents and Chemotherapy, March 2001, p. 781-785, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.781-785.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Pharmacodynamic Properties of Colistin and Colistin Methanesulfonate against Pseudomonas aeruginosa Isolates from Patients with Cystic Fibrosis

Jian Li,1 John Turnidge,2,* Robert Milne,1 Roger L. Nation,1 and Kingsley Coulthard1,3

Centre for Pharmaceutical Research, University of South Australia, Adelaide,1 and Department of Infectious Diseases2 and Pharmacy Department,3 Women's and Children's Hospital, North Adelaide, South Australia, Australia

Received 18 April 2000/Returned for modification 20 August 2000/Accepted 13 December 2000

The in vitro pharmacodynamic properties of colistin and colistin methanesulfonate were investigated by studying the MICs, time-kill kinetics, and postantibiotic effect (PAE) against mucoid and nonmucoid strains of Pseudomonas aeruginosa isolated from patients with cystic fibrosis. Twenty-three clinical strains, including multiresistant strains, and one type strain were selected 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 were significantly higher and ranged from 4 to 16 mg/liter. The time-kill kinetics were investigated with three strains at drug concentrations ranging from 0.5 to 64 times the MIC. Colistin showed extremely rapid killing, resulting in complete elimination at the highest concentrations within 5 min, while colistin methanesulfonate killed more slowly, requiring a concentration of 16 times the MIC to achieve complete killing within 24 h. Colistin exhibited a significant PAE of 2 to 3 h at 16 times the MIC against the three strains after 15 min of exposure. For colistin methanesulfonate, PAEs were shorter at the concentrations tested. Colistin methanesulfonate had lower overall bactericidal and postantibiotic activities than colistin, even when adjusted for differences in MICs. Our data suggest that doses of colistin methanesulfonate higher than the recommended 2 to 3 mg/kg of body weight every 12 h may be required for the effective treatment of P. aeruginosa infections in cystic fibrosis patients.

* Corresponding author. Mailing address: Department of Microbiology and Infectious Diseases, Women's and Children's Hospital, 72 King William Rd., North Adelaide, South Australia 5006, Australia. Phone: 61 8 8204 6873. Fax: 61 8 8204 6051. E-mail: turnidgej{at}wch.sa.gov.au.

Antimicrobial Agents and Chemotherapy, March 2001, p. 781-785, Vol. 45, No. 3
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.3.781-785.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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