Synergistic activity of colistin and ceftazidime against multiantibiotic-resistant Pseudomonas aeruginosa in an in vitro pharmacodynamic model.

Abstract:

: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, > or =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-log(10) 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 < or =18 mg/liter.

authors

Gunderson BW,Ibrahim KH,Hovde LB,Fromm TL,Reed MD,Rotschafer JC

doi

10.1128/aac.47.3.905-909.2003

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

905-9

issue

3

eissn

0066-4804

issn

1098-6596

journal_volume

47

pub_type

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