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Antimicrobial Agents and Chemotherapy, March 2003, p. 905-909, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.905-909.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Synergistic Activity of Colistin and Ceftazidime against Multiantibiotic-Resistant Pseudomonas aeruginosa in an In Vitro Pharmacodynamic Model

Brent W. Gunderson,1 Khalid H. Ibrahim,1 Laurie B. Hovde,1 Timothy L. Fromm,1 Michael D. Reed,2 and John C. Rotschafer1*

The University of Minnesota College of Pharmacy, Department of Experimental and Clinical Pharmacology, Minneapolis, Minnesota,1 Rainbow Babies and Children's Hospital, Cleveland, Ohio2

Received 20 May 2002/ Returned for modification 29 September 2002/ Accepted 25 November 2002

Despite the marketing of a series of new antibiotics for antibiotic-resistant gram-positive bacteria, no new agents for multiple-antibiotic-resistant gram-negative infections will be available for quite some time. Clinicians will need to find more effective ways to utilize available agents. Colistin is an older but novel antibiotic that fell into disfavor with clinicians some time ago yet still retains a very favorable antibacterial spectrum, especially for Pseudomonas and Acinetobacter spp. Time-kill curves for two strains of multiantibiotic-resistant Pseudomonas aeruginosa were generated after exposure to colistin alone or in combination with ceftazidime or ciprofloxacin in an in vitro pharmacodynamic model. MICs of colistin, ceftazidime, ciprofloxacin, piperacillin-tazobactam, imipenem, and tobramycin were 0.125, >=32, >4, >128/4, 16, and >16 mg/liter, respectively. Colistin showed rapid, apparently concentration-dependent bactericidal activity at concentrations between 3 and 200 mg/liter. We were unable to detect increased colistin activity at concentrations above 18 mg/liter due to extremely rapid killing. The combination of colistin and ceftazidime was synergistic (defined as at least a 2-log10 drop in CFU per milliliter from the count obtained with the more active agent) at 24 h. Adding ciprofloxacin to colistin did not enhance antibiotic activity. These data suggest that the antibacterial effect of colistin combined with ceftazidime can be maximized at a peak concentration of <=18 mg/liter.

* Corresponding author. Mailing address: University of Minnesota College of Pharmacy, Department of Experimental and Clinical Pharmacology, 7-170 Weaver-Densford Hall, 308 Harvard St. SE, Minneapolis, MN 55455. Phone: (612) 624-2183. Fax: (612) 625-9931. E-mail: rotsc001{at}umn.edu.

Antimicrobial Agents and Chemotherapy, March 2003, p. 905-909, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.905-909.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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