Antibiotic rotation and development of gram-negative antibiotic resistance

Am J Respir Crit Care Med. 2005 Mar 1;171(5):480-7. doi: 10.1164/rccm.200401-070OC. Epub 2004 Oct 29.


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Colony Count, Microbial
  • Drug Administration Schedule
  • Drug Resistance, Bacterial*
  • Female
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Infection Control / methods
  • Male
  • Middle Aged
  • Prospective Studies
  • Quinolones / administration & dosage
  • Risk Factors
  • beta-Lactam Resistance


  • Anti-Bacterial Agents
  • Quinolones