title: In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp. by levofloxacin and ciprofloxacin alone and in combination with beta-lactams and amikacin.
abstract: OBJECTIVE
  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 >or=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 beta-lactams and amikacin reduces the risk for in vitro selection of resistant P. aeruginosa and Acinetobacter spp.
authors.affiliation: Laboratory of Clinical Microbiology, Department of Clinical Sciences, L. Sacco Teaching Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy. lorenzo.drago@unimi.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Drago
authors.forename: Elena
authors.initials: E
authors.lastname: De Vecchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Nicola
authors.forename: Loredana
authors.initials: L
authors.lastname: Tocalli
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Gismondo
mesh_terms: D000150:Acinetobacter / Q000187:drug effects* / Q000235:genetics; D000583:Amikacin / Q000008:administration & dosage / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000494:pharmacology; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009154:Mutation; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D047090:beta-Lactams / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002939:Ciprofloxacin; D064704:Levofloxacin; D000583:Amikacin; D015242:Ofloxacin