Outbreak of resistant Pseudomonas aeruginosa infections during a quarterly cycling antibiotic regimen.

BACKGROUND: Antibiotic cycling or rotation of antimicrobial agent classes has been proposed to combat antimicrobial resistance. METHODS: A prospective cohort study was conducted in a medical intensive care unit (ICU) of a university hospital between December 1, 2000, and September 30, 2002, as part of a three-center trial under the aegis of the U.S. Centers for Disease Control and Prevention. Patients admitted to the medical ICU for > 48 h were enrolled, and demographic and microbiological data were collected until discharge or death. Baseline data were collected for four months (12/1/00 to 3/31/01) and compared with data collected after institution of a quarterly cycling regimen (cycle order: Cefepime, ciprofloxacin, piperacillin-tazobactam, imipenem-cilastatin) for the empiric treatment of gram-negative infections (4/01/01 to 9/30/02). RESULTS: Of 1,074 consecutive admissions, 301 were enrolled, 59 during baseline and 242 during the cycling periods. An outbreak of multi-drug resistant Pseudomonas aeruginosa followed cycle 2 (cefepime), coinciding with cycles 3 and 4 (ciprofloxacin and piperacillin-tazobactam) (80.0 and 73.7 vs. 37.3 isolates/100 patients enrolled for cycles 3/4 and baseline, respectively; p = 0.04). Acinetobacter spp. were isolated less frequently during the cycling periods (15.3 vs. 1.2 isolates/100 patients for baseline and cycling periods, respectively; p > or = 0.01). The crude hospital mortality rate was similar (24/59 [41%] baseline vs. 73/242 [30%] cycling; p = 0.16) between periods. However, the percentage of patients admitted to the medical ICU who subsequently acquired an infection followed by in-hospital death was higher at baseline than during cycling: 15/59 (25.4%) vs. 33/242 (13.6%)(p = 0.04). CONCLUSIONS: In this study, the cycling strategy was not definitively associated with beneficial changes in unit epidemiology and in fact may have contributed to an outbreak of multi-drug resistant P. aeruginosa.

Can we define the ideal duration of antibiotic therapy?

BACKGROUND: Because of the increasing development of antimicrobial resistance, there is a greater responsibility within the medical community to limit the exposure of patients to antibiotics. We tested the hypothesis that shorter courses of antibiotics are associated with similar or better results than longer durations. We also sought to investigate the difference between a fixed duration of therapy and one based on physiologic measures such as fever and leukocytosis. METHODS: All infectious episodes on the general surgery units of the University of Virginia Health System from December 15, 1996, to July 31, 2003, were analyzed retrospectively for the relation between the duration of antibiotic therapy and infectious complications (recurrent infection with the same organism or at the same site). All infections associated with either fever or leukocytosis were categorized into quartiles on the basis of the absolute length of antibiotic administration or the duration of treatment following resolution of fever or leukocytosis. Multivariate logistic regression models were developed to estimate the independent risk of recurrence associated with a longer duration of antibiotic use. RESULTS: Of the 5,561 treated infections, 4,470 were associated with fever (temperature > or =38 degrees C) or leukocytosis (white blood cell count > or =11,000/mm(3)). For all infections, whether analyzed by absolute duration or time from resolution of leukocytosis or fever, the first or second quartiles (0-12 days, 0-9 days, 0-9 days, respectively) were associated with the lowest recurrence rates (14-18%, 17-23%, 18-19%, respectively). Individual analysis of intra-abdominal infections and pneumonia yielded similar results. The fixed-duration groups received fewer days of antibiotics on average, with outcomes similar to those in the physiologic parameters group. CONCLUSIONS: Shorter courses of antibiotics were associated with similar or fewer complications than prolonged therapy. In general, adopting a strategy of a fixed duration of therapy, rather than basing duration on resolution of fever or leukocytosis, appeared to yield similar outcomes with less antibiotic use.