title: Activity of gatifloxacin and ciprofloxacin in combination with other antimicrobial agents.
abstract: The influence of non-quinolone antimicrobial agents on the antibacterial activities of gatifloxacin and ciprofloxacin was determined using chequerboard, fractional inhibitory concentration, (FIC) and time-kill analysis methods. In the chequerboard method, the quinolones were tested in combination with ten antimicrobial agents (macrolides, aminoglycosides, beta-lactams, vancomycin, rifampicin and chloramphenicol) against five bacterial strains (one strain each of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and Streptococcus pneumoniae). In no incidence was antagonism (FIC > or = 4) or synergy (FIC < or = 0.5) observed; all dual drug combinations involving gatifloxacin or ciprofloxacin showed additivity/indifference (FIC > 0.5, < 4). By time-kill analysis, the strains were tested at a quinolone concentration equal to 8 x MIC in combination with a second antibiotic at 0.5xits MIC. These combinations killed non-enterococcal strains at rates similar to those with quinolones alone. However, rifampicin and chloramphenicol were often antagonistic (100-fold lesser killing) to the lethal action of gatifloxacin and ciprofloxacin against E. faecalis. These findings indicate that, with the exception of E. faecalis, the antibacterial activities of quinolones are generally additive/indifferent to those of other antimicrobial agents.
authors.affiliation: Department of Microbiology, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06457, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gradelski
authors.forename: B
authors.initials: B
authors.lastname: Kolek
authors.forename: D P
authors.initials: DP
authors.lastname: Bonner
authors.forename: L
authors.initials: L
authors.lastname: Valera
authors.forename: B
authors.initials: B
authors.lastname: Minassian
authors.forename: J
authors.initials: J
authors.lastname: Fung-Tomc
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004336:Drug Antagonism; D004338:Drug Combinations; D004347:Drug Interactions; D004357:Drug Synergism; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D000077734:Gatifloxacin