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

• Published in: Journal of antimicrobial chemotherapy Vol. 56; no. 2; pp. 353 - 359
• Main Authors: Drago, Lorenzo, De Vecchi, Elena, Nicola, Lucia, Tocalli, Loredana, Gismondo, Maria Rita
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2005; Oxford Publishing Limited (England)
• Subjects: Acinetobacter - drug effects; Acinetobacter - genetics; Amikacin - administration & dosage; Amikacin - pharmacology; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; beta-Lactams - administration & dosage; beta-Lactams - pharmacology; Biological and medical sciences; Ciprofloxacin - administration & dosage; Ciprofloxacin - pharmacology; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Drug Therapy, Combination - administration & dosage; Drug Therapy, Combination - pharmacology; fluoroquinolones; Levofloxacin; Medical sciences; Microbial Sensitivity Tests; Mutation; mutation frequencies; Ofloxacin - administration & dosage; Ofloxacin - pharmacology; Pharmacology. Drug treatments; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - genetics; β-lactams; Pseudomonadales; Levofloxacin; Amikacin; Selection; Neisseriaceae; mutation frequencies; Fluoroquinolone derivatives; Bacteria; Micrococcales; Pseudomonadaceae; Acinetobacter; Genetics; Pseudomonas aeruginosa; Quinolone derivatives; Drug combination; β-Lactams; In vitro; Resistance; Antibiotic; Aminoglycoside; Frequency; Mutation; fluoroquinolones; Antibacterial agent; Ciprofloxacin
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dki204

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.