Nature of gram-negative rod antibiotic resistance during antibiotic rotation

Heather L. Evans, Meghan L. Milburn, Michael G. Hughes, Robert L. Smith, T. W. Chong, Daniel P. Raymond, Shawn J. Pelletier, Timothy L. Pruett, Robert G. Sawyer

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Purpose: The aim of this study was to characterize the evolution of gram-negative antibiotic resistance during a study of empiric antibiotic rotation. Methods: We showed previously that quarterly rotation of a single antibiotic class is inferior to cycling two antibiotics per quarter for empiric treatment of gram-negative rod (GNR) infections, as evidenced by increased incidence of antibiotic-resistant GNR (rGNR) infections. Resistance patterns were examined by quantifying GNRs resistant to one or more of the following drug classes: Aminoglycosides, cephalosporins, carbapenems, fluoroquinolones, or piperacillin-tazobactam. For all rGNR isolates, the mean number of antibiotic classes to which an organism was resistant was calculated per quarter, as was the number of rGNR species. Results: Single-antibiotic rotation (SAR) was associated with significant increases in the incidence of piperacillin-tazobactam (p < 0.0005) and cephalosporin (p = 0.003) resistance, reaching nearly 25% and 30% of rGNR isolates respectively, most notably during the quarter of designated cephalosporin use (VI). Multi-drug resistance emerged over time; resistant classes/resistant GNR isolates ranged from 1.2 in the dual-antibiotic rotation (DAR) to 1.9 in the SAR period (p = 0.02). Resistance was evident in an increasing number of unique GNR species. On average, 1.3 species were isolated per month in the DAR period and 3.0/month in the SAR period (p = 0.004), but proportionally, no single GNR species became significantly more resistant across time. Compared to only 5.8% in the DAR period, 29% noncompliance was observed in the SAR, with a six-fold increase in the use of nonscheduled empiric antibiotics due to the presence of an organism resistant to the scheduled rotation drug. Conclusions: A single-antibiotic rotation is associated with increased incidence and heterogeneity of resistant GNR isolates, as well as increased multiple-drug-class resistance. The attenuation of resistance observed in the single-antibiotic rotation may reflect the effect of unintended antibiotic heterogeneity driven by increasing resistance to the antibiotic class recommended for use each quarter. This suggests that reliance on a single antibiotic class for empiric treatment of GNR infection exerts sufficient pressure within the environment to encourage the development of diversified resistance, as well as cross-resistance over antibiotic classes, thus narrowing the availability of effective antibiotic treatment.

Original languageEnglish (US)
Pages (from-to)223-231
Number of pages9
JournalSurgical Infections
Issue number2
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Surgery
  • Microbiology (medical)
  • Infectious Diseases


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