title: In vitro synergy and selection of resistance by fluoroquinolones plus amikacin or beta-lactams against extended-spectrum beta-lactamase-producing Escherichia coli.
abstract: This study compared the potential synergy of levofloxacin and ciprofloxacin in combination with cefepime, ceftazidime, imipenem, piperacillin/tazobactam or amikacin, against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli by using checkerboard and time kill studies. Moreover, selection of resistance was determined by frequency of mutations and by calculating the increase in minimum inhibitory concentrations (MICs) after five serial subcultures on antibiotic-containing plates. Synergy occurred more often with levofloxacin combined with imipenem (7/10 strains) and with levofloxacin or ciprofloxacin with amikacin (10/10) than for the other combinations. Time kill studies showed synergy for levofloxacin combined with amikacin, ceftazidime, imipenem or piperacillin/tazobactam, and for ciprofloxacin combined with amikacin, cefepime or imipenem. Antibiotic combinations selected for resistance less frequently than antibiotics alone. Mutation frequency was <10(-12) for all combinations. In conclusion, the combination of a fluoroquinolone with a beta-lactam or amikacin may provide improved antimicrobial activity and help limit the occurrence of resistance in ESBL-producing E. coli strains.
authors.affiliation: Lab Clinical Microbiology, Dept Clinical Science L Sacco, Via GB Grassi 74, 20157 Milano, Italy. lorenzo.drago@unimi.it
authors.forename: L
authors.initials: L
authors.lastname: Drago
authors.forename: E
authors.initials: E
authors.lastname: De Vecchi
authors.forename: L
authors.initials: L
authors.lastname: Nicola
authors.forename: D
authors.initials: D
authors.lastname: Legnani
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: M R
authors.initials: MR
authors.lastname: Gismondo
mesh_terms: D000583:Amikacin / Q000008:administration & dosage; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology*; D024841:Fluoroquinolones / Q000008:administration & dosage; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D001618:beta-Lactamases / Q000096:biosynthesis*; D047090:beta-Lactams / Q000008:administration & dosage
chemical_list: D024841:Fluoroquinolones; D047090:beta-Lactams; D000583:Amikacin; D001618:beta-Lactamases