title: Comparison of the bactericidal activity of ciprofloxacin alone and in combination with selected antipseudomonal beta-lactam agents against clinical isolates of Pseudomonas aeruginosa.
abstract: The bactericidal activity of ciprofloxacin against 60 clinical isolates of Pseudomonas aeruginosa was evaluated by exposing replicating microorganisms to concentrations ranging from 0.12 to 2 micrograms/ml for 48 hr. In addition, ciprofloxacin was combined with selected antipseudomonal beta-lactams using subinhibitory concentrations (1/4 x MIC, 1/2 x MIC) of each. We found that a concentration of 2 micrograms/ml of ciprofloxacin resulted in bactericidal activity (greater than or equal to 99.9% killing of the final inoculum) at 8 and 12 hr for the highest percentage of isolates (95 and 96.7%, respectively). At the breakpoint concentration (1 micrograms/ml), there was bactericidal activity against 81.7% of these isolates at 8 hr and 78.7% at 12 hr. By 24 and 48 hr, regrowth was frequently seen for concentrations of 1 and 2 micrograms/m (76.7 and 41.7%, respectively). This regrowth represented limited progression of resistance (4- to 16-fold increase in MICs) to ciprofloxacin without cross-resistance to other classes of antibiotics. The combinations containing ciprofloxacin and beta-lactam agent were synergistic for isolates that were susceptible to both agents. Moreover, the combinations prevented the emergence of resistance to either drug.
authors.affiliation: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: C W
authors.initials: CW
authors.lastname: Stratton
authors.forename: J J
authors.initials: JJ
authors.lastname: Franke
authors.forename: L S
authors.initials: LS
authors.lastname: Weeks
authors.forename: F A
authors.initials: FA
authors.lastname: Manion
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004355:Drug Stability; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000494:pharmacology; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002939:Ciprofloxacin