In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with β-lactams and amikacin

Lorenzo Drago, Elena De Vecchi, Lucia Nicola, Loredana Tocalli, Maria Rita Gismondo

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The aim of this study was to evaluate the ability of levofloxacin and ciprofloxacin alone and in combination with either ceftazidime, cefepime, imipenem, piperacillin-tazobactam or amikacin to select for antibiotic-resistant mutants of Pseudomonas aeruginosa and Acinetobacter spp. Methods: Clinical strains of P. aeruginosa (n=5) and Acinetobacter spp. (n=5) susceptible to all the drugs used in the study were assayed. Development of resistance was determined by multi-step and single-step methodologies. For multi-step studies, MICs were determined after five serial passages on antibiotic-gradient plates containing each antibiotic alone or in combination with levofloxacin or ciprofloxacin. Acquisition of resistance was defined as an increase of ≥4-fold from the starting MIC. In single-step studies, the frequency of spontaneous mutations was calculated after a passage on plates containing antibiotics alone and in combinations at concentrations equal to the highest NCCLS breakpoints. Results: Serial passages on medium containing single antibiotics resulted in increased MICs for each antibiotic; MIC increases were limited by antibiotics in combination. A decrease in the number of strains with MICs above the NCCLS breakpoints occurred when fluoroquinolones were combined with a second antibiotic for both P. aeruginosa and Acinetobacter spp. isolates. Frequencies of mutation were higher for antibiotics alone than for combinations. Conclusions: Use of combinations of fluoroquinolones with β-lactams and amikacin reduces the risk for in vitro election of resistant P. aeruginosa and Acinetobacter spp.

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume56
Issue number2
DOIs
Publication statusPublished - Aug 2005

Keywords

  • β-lactams
  • Fluoroquinolones
  • Mutation frequencies

ASJC Scopus subject areas

  • Microbiology
  • Pharmacology

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