Characterization of fluoroquinolone and carbapenem susceptibilities in clinical isolates of levofloxacin-resistant Pseudomonas aeruginosa

Chemotherapy. 2005 May;51(2-3):70-5. doi: 10.1159/000085612. Epub 2005 May 4.

Abstract

Background: Pseudomonas aeruginosa can rapidly acquire resistance to antibiotics, including fluoroquinolones and carbapenems.

Methods: We characterized fluoroquinolone, carbapenem and other beta-lactam susceptibilities and analyzed fluoroquinolone and carbapenem resistance in 16 clinical isolates of levofloxacin-resistant P. aeruginosa.

Results: All levofloxacin-resistant isolates showed high MICs (> or =32 microg/ml) for fluoroquinolones including norfloxacin, levofloxacin, sparfloxacin, gatifloxacin and pazufloxacin, whereas the MICs for sitafloxacin were between 2 and 16 microg/ml. These isolates had both a Thr83Ile mutation in GyrA and a Ser87Leu mutation in ParC. An additional mutation, Glu469Asp in GyrB, was detected in 3 isolates. Three of 16 isolates found during antibiotic therapy showed resistance to carbapenems (MIC, 16-32 microg/ml) because of a reduced production of OprD. Fluoroquinolones, beta-lactams and sulfamethoxazole-trimethoprim were used for 3 months before the isolation of levofloxacin-resistant P.aeruginosa.

Conclusions: Emergence of resistant isolates to both fluoroquinolones and carbapenems during antibiotic therapy is a serious clinical problem. Our results suggest that susceptibilities to fluoroquinolones as well as carbapenems should be monitored during a prolonged course of antibiotic therapy against P. aeruginosa infection.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenems / pharmacology*
  • Carbapenems / therapeutic use
  • DNA Gyrase / genetics
  • DNA Topoisomerase IV / genetics
  • Drug Resistance, Bacterial / drug effects*
  • Drug Resistance, Bacterial / genetics
  • Fluoroquinolones / pharmacology*
  • Fluoroquinolones / therapeutic use
  • Humans
  • Levofloxacin
  • Microbial Sensitivity Tests
  • Mutation
  • Ofloxacin / pharmacology
  • Ofloxacin / therapeutic use
  • Porins / biosynthesis
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / isolation & purification

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Fluoroquinolones
  • Porins
  • OprD protein, Pseudomonas aeruginosa
  • Levofloxacin
  • Ofloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase