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Comparison of antimicrobial cycling and mixing strategies in two medical intensive care units*

Martínez, José-Antonio MD, PhD; Nicolás, Josep-María MD, PhD; Marco, Francesc MD, PhD; Horcajada, Juan-Pablo MD, PhD; Garcia-Segarra, Gloria MD; Trilla, Antoni MD, PhD; Codina, Carles PhD; Torres, Antoni MD, PhD; Mensa, Josep MD

doi: 10.1097/01.CCM.0000195010.63855.45
Clinical Investigations

Objective: To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting.

Design: Prospective, open, comparative study of two strategies of antibiotic use.

Setting: Two medical intensive care units of a university hospital.

Patients: A total of 346 patients admitted for ≥48 hrs to two separate medical intensive care units during an 8-month period.

Interventions: Patients, who according to the attending physician’s judgment required an anti-Pseudomonas regimen, were assigned to receive cefepime/ceftazidime, ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. “Cycling” was accomplished by prescribing one of these antibiotics during 1 month each. “Mixing” was accomplished by using the same order of antibiotic administration on consecutive patients. Interventions were carried out during two successive 4-month periods, starting with mixing in one unit and cycling in the other.

Measurements and Main Results: Swabbing of nares, pharynx, and rectum and culture of respiratory secretions were obtained thrice weekly. The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention. The scheduled cycling of antibiotics was only partially successful. Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period, it never accounted for >45% of all anti-Pseudomonas antimicrobials administered. During mixing, a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was a trend toward a more frequent acquisition of resistance to ceftazidime (p = .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed.

Conclusions: In critically ill medical patients, a strategy of monthly rotation of anti-Pseudomonas β-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected β-lactams.

From the Departments of Infectious Diseases (JAM, JPH, JM), Medical Intensive Care Unit (JMN, GGS), Microbiology Laboratory (FM), Unit for Evaluation, Supporting and Prevention (AT), Pharmacy (CC), and Respiratory Intensive Care Unit-ICPTC (AT). Hospital Clínic, IDIBAPS -University of Barcelona. Spain.

Supported, in part, by grant N-019/02/2000 from the Agencia d’Avaluació i Recerca Médiques de la Generalitat de Catalunya, Barcelona, Spain, and, in part, by funds of the Red Gira (N-2000) and Red Respira (N-2000) of the Instituto de Salud Carlos III, Madrid, Spain.

Dr. J.A. Martínez has received honoraria from Bayer, Pfizer, and Merck. Dr. A. Torres has received honoraria from Bayer. Dr. J. Mensa has received honoraria from Bayer, Aventis, Pfizer, and Merck. The remaining authors have no financial interest to disclose.

Address requests for reprints to: José-Antonio Martínez, MD, PhD, Department of Infectious Diseases, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain. E-mail:

© 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins