Journal Article

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

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

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 2, pages 353-359
Published in print August 2005 | ISSN: 0305-7453
Published online June 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki204
In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with β-lactams and amikacin

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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 selection of resistant P. aeruginosa and Acinetobacter spp.

Keywords: mutation frequencies; β-lactams; fluoroquinolones

Journal Article.  3899 words. 

Subjects: Medical Oncology ; Critical Care

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