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Cycling empirical antimicrobial agents to prevent emergence of antimicrobial-resistant Gram-negative bacteria among intensive care unit patients

Warren, David K. MD; Hill, Holly A. MD, PhD; Merz, Liana R. MPH; Kollef, Marin H. MD; Hayden, Mary K. MD; Fraser, Victoria J. MD; Fridkin, Scott K. MD

doi: 10.1097/01.CCM.0000147685.79487.28
Clinical Investigations

Objective: To determine the impact of the rotation of antimicrobial agents on the rates of infection, intestinal colonization, and acquisition with antimicrobial-resistant Gram-negative bacteria.

Design: Pre- and postintervention design.

Setting: A 19-bed, medical intensive care unit.

Patients: Individuals admitted to the study unit for >48 hrs.

Interventions: After a 5-month baseline observation period, four classes of antimicrobial agents with Gram-negative activity were cycled at 3- to 4-month intervals for 24 months.

Measurements and Main Results: The primary outcome was the acquisition rate of antimicrobial resistance among Enterobacteriaceae and Pseudomonas aeruginosa obtained from rectal swab cultures performed on admission, weekly during the patients’ stay, and at discharge. Rates and microbiology of nosocomial bloodstream infections and ventilator-associated pneumonia were also compared between baseline and cycling periods. The cycling program resulted in a significant change in prescribing practices; the predominant agent used changed with each cycle. Among study patients who were not already colonized with a resistant organism, the rate of acquisition of enteric colonization with bacteria resistant to any of the target drugs remained stable during the cycling period for P. aeruginosa (relative rate, 0.96; 95% confidence Interval, 0.47–2.16) and Enterobacteriaceae (relative rate, 1.57; 95% confidence interval, 0.80–3.43). Hospital-wide, P. aeruginosa from routine clinical cultures resistant to the target drugs increased during the cycling period. The proportion of Gram-negative bacteria isolated from cases of nosocomial bloodstream infection (29% baseline vs. 26% cycling; p = .11) and ventilator-associated pneumonia (80% vs. 41%; p = .06) did not significantly differ.

Conclusions: In this study, antimicrobial cycling did not result in a significant change in enteric acquisition of resistant Gram-negative bacteria among intensive care unit patients.

From the Department of Medicine (DKW, LRM, MHK, VJF), Washington University School of Medicine, St. Louis, MO; Division of Healthcare Quality Promotion (HAH) and Division of Bacterial and Mycotic Diseases (SKF), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and Department of Medicine (MKH), Rush University Medical Center, Chicago, IL.

Supported, in part, by Cooperative Agreements U50/CCU717925-CDC and UR8/CCU715087-03-CDC from the Centers for Disease Control and Prevention and by Career Development Award K23 AI050585-01A1 from the National Institutes of Health (DKW).

Use of trade names and commercial sources is for identification only and does not imply endorsement by the Public Health Service or the Department of Health and Human Services.

Address requests for reprints to: David K. Warren, MD; Division of Infectious Diseases, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue Ave., St. Louis, MO 63110. E-mail:

© 2004 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins