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

Abstract

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.