Pseudomonas aeruginosa is not just in the intensive care unit any more: implications for empirical therapy

To improve empirical therapy for Pseudomonas aeruginosa using susceptibility surveillance by unit type (intensive care unit vs. nonintensive care unit) and to optimize antibacterial dosing using pharmacodynamic profiling.

Prospective multicentered surveillance study.

Thirteen U.S. hospitals.

Seven hundred thirty-six nonduplicate, nonurine P. aeruginosa isolates collected from first quarter, 2009, to second quarter, 2010.

None.

Isolate minimum inhibitory concentrations (MICs) to ten antimicrobials (three carbapenems-doripenem, imipenem and meropenem-plus three other β-lactams, two fluoroquinolones, and two aminoglycosides) were determined by broth microdilution. Wilcoxon rank sums compared MIC distributions by unit type; chi-square tests compared agents and antibiotic classes. Cumulative fraction of response predicted likelihood of pharmacodynamic target attainment for antimicrobial dosing regimens vs. observed MIC distributions. Nonintensive care units contributed 65% of isolates with identifiable locations (n = 614). Carbapenem class nonsusceptibility nonsusceptible to 1 or more agent) differed by location (35% intensive care unit, 27% nonintensive care unit, p = .03); no other classes differed. Multidrug resistance (nonsusceptible to one or more drug in each of all four classes) was 12% intensive care unit and 5% in nonintensive care units (p < .01). Carbapenem MIC profile in intensive care units was (agent, MIC50, MIC90, percent susceptibility): Doripenem, 1, 8, 69%; imipenem, 2, 16, 67%; and meropenem, 1, 32, 70%; and by nonintensive care units: Doripenem, 0.5%, 8%, 78%; imipenem, 1, 16, 75%; and meropenem, 1, 16, 82%. MIC distributions differed by unit type only for imipenem (p < .01). The remaining nine agents were not different. Standard carbapenem regimens resulted in cumulative fraction of response (regimen, intensive care unit, nonintensive care unit): Doripenem at 500 mg every 8 hrs 1-hr infusion, 73%, 79%; imipenem at 500 mg every 6 hrs 0.5-hr infusion, 62%, 69%; meropenem at 500 mg every 6 hrs 0.5-hr infusion, 67%, 76%. More aggressive doses and prolonged infusion improved cumulative fraction of response: Doripenem at 1000 mg every 8 hrs 4-hr infusion, 92%, 97%; imipenem at 1000 mg every 8 h 3-h infusion, 77%, 83%; meropenem at 2000 mg every 8 hrs 3-hr infusion, 87%, 94%.

Although multidrug-resistant and nonsusceptible carbapenem phenotypes were more common in intensive care units, the prevalence of P. aeruginosa among initial cultures of systemic isolates taken elsewhere was high (65%). Unit-specific antibiograms could benefit empirical therapy decisions; consideration of carbapenem, dose, and infusion time may enhance outcomes for P. aeruginosa infection.