title: In-vitro synergy and mechanism of interaction between vancomycin and ciprofloxacin against enterococcal isolates.
abstract: In-vitro synergy between vancomycin and ciprofloxacin against 44 enterococcal isolates was studied. Synergy occurred in chequerboard MIC determinations with six Enterococcus faecium strains resistant to both vancomycin and ciprofloxacin. The combination was additive for strains susceptible to one or both antibiotics. Time-kill studies involving selected strains with different susceptibility patterns confirmed the chequerboard results. The effect of ciprofloxacin on the induction of vancomycin resistance was compared in two vancomycin-resistant strains of E. faecium. Sub-inhibitory concentrations of ciprofloxacin prevented induction of vancomycin resistance in a ciprofloxacin-resistant strain, but not in a ciprofloxacin-susceptible strain. Membranes isolated from vancomycin-resistant ciprofloxacin-resistant cultures grown with vancomycin and ciprofloxacin at < or = 8 mg/L (0.125 x MIC) expressed a 39.5-kDa membrane protein involved in the expression of vancomycin resistance, but the protein was not detected in membranes from cultures grown in ciprofloxacin 16 mg/L. These findings indicated that a vancomycin-ciprofloxacin combination can be synergic against enterococci resistant to both vancomycin and ciprofloxacin, but would be unlikely to offer any advantage in the treatment of enterococcal infections because of the high concentrations required.
authors.affiliation: Lilly Research Laboratories, Eli Lilly & Company, Indianapolis, IN 46285-0428.
authors.forename: S
authors.initials: S
authors.lastname: Unal
authors.forename: J
authors.initials: J
authors.lastname: Flokowitsch
authors.forename: D L
authors.initials: DL
authors.lastname: Mullen
authors.forename: D A
authors.initials: DA
authors.lastname: Preston
authors.forename: T I
authors.initials: TI
authors.lastname: Nicas
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D002462:Cell Membrane / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D016984:Enterococcus faecium / Q000187:drug effects* / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002939:Ciprofloxacin; D014640:Vancomycin