title: Antibiotic rotation and development of gram-negative antibiotic resistance.
abstract: 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 intensive care unit. 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 2,520 cultures analyzed. Adherence to antibiotic protocol was 96%. Overall antibiotic use increased with 24%. Acquisition rates with resistant bacteria were highest during levofloxacin exposure (relative risk [RR] 3.2; 95% confidence interval [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 (hazard ratio 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 intensive care units.
authors.affiliation: Department of Surgery, Eijkman-Winkler Institute for Microbiology, Infectious Disease and Inflammation, University Medical Center Utrecht, Heidelberglaan 100, PO Box 3508 GA, Utrecht, The Netherlands. hjvloon@yahoo.com
authors.forename: Harald J
authors.initials: HJ
authors.lastname: van Loon
authors.forename: Menno R
authors.initials: MR
authors.lastname: Vriens
authors.forename: Ad C
authors.initials: AC
authors.lastname: Fluit
authors.forename: Annet
authors.initials: A
authors.lastname: Troelstra
authors.forename: Christiaan
authors.initials: C
authors.lastname: van der Werken
authors.forename: Jan
authors.initials: J
authors.lastname: Verhoef
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D017053:Infection Control / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015363:Quinolones / Q000008:administration & dosage; D012307:Risk Factors; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015363:Quinolones