Published ahead of print on October 29, 2004, doi:10.1164/rccm.200401-070OC Am. J. Respir. Crit. Care Med., Volume 171, Number 5, March 2005, 480-487 A more recent version of this article appeared on March 1, 2005
Submitted on January 28, 2004 Antibiotic Rotation and Development of Gram-Negative Antibiotic ResistanceHarald J van Loon1*,1 Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands, 2 Eijkman-Winkler Institute for Microbiology, Infectious Disease and Inflammation, University Medical Center Utrecht, Utrecht, The Netherlands, 3 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Hospital Hygiene and Infection Prevention, University Medical Center Utrecht, Utrecht, The Netherlands, 4 Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands, 5 Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands; Eijkman-Winkler Institute for Microbiology, Infectious Disease and Inflammation, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Hospital Hygiene and Infection Prevention, University Medical Center Utrecht, Utrecht, The Netherlands, 6 Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, The Netherlands * To whom correspondence should be addressed. E-mail: hjvloon{at}yahoo.com.
To attain a better understanding of antibiotic cycling and its effects on the epidemiology of antibiotic resistance in Gram-negative microorganisms, two different antibiotic classes (quinolone and beta-lactam) were cycled during four 4-month periods in a surgical ICU. Respiratory aspirates and rectal swabs were obtained and DNA-fingerprinting was performed. Primary endpoint of the study was the acquisition rate with Gram-negative bacteria resistant to the antibiotic of choice during each cycle. Secondary endpoints were changes in endemic prevalence of resistant bacteria and the relative importance of cross-transmission. In all, 388 patients were included and 2520 cultures analyzed. Adherence to antibiotic protocol was 96%. Overall antibiotic use increased with 24%. Acquisition rates with resistant bacteria were highest during levofloxacin exposure (RR 3.2; 95%CI:1.4-7.1) and piperacillin/tazobactam exposure (RR 2.4; 95% CI 1.2-4.8). The relative importance of cross-transmission decreased during the study. For individual patients treatment with levofloxacin was the only independent risk factor for acquisition of levofloxacin-resistant bacteria (HR 12.6; 95% CI 3.8-41.6). Potential for selection of antibiotic-resistant Gram-negative bacteria during periods of homogeneous exposure increased from cefpirome to piperacillin/tazobactam to levofloxacin. Cycling of homogeneous antibiotic exposure is unlikely to control the emergence of Gram-negative antimicrobial resistance in ICUs. Key words: Antibiotic resistance, antibiotic rotation, cycling antibiotics, gram-negative microorganisms, antibiotic therapy
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