title: Dose ranging and fractionation of intravenous ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of infection.
abstract: The effect of dose or dose interval on the pharmacodynamics of simulated high-dose intravenous ciprofloxacin therapy on infection due to Pseudomonas aeruginosa and Staphylococcus aureus was studied in an in vitro hollow-fiber model of infection. Simulated doses of 1,200 mg of ciprofloxacin per day as either 400 mg every 8 h or 600 mg every 12 h against P. aeruginosa resulted in selection of ciprofloxacin-resistant bacteria. The results with one test strain that was isolated from a patient prior to administration of intravenous ciprofloxacin demonstrated selection of a gyrA mutant in the model, as had occurred in vivo. A single 1,200-mg dose every 24 h did not select for bacterial resistance; however, breakthrough regrowth of ciprofloxacin-susceptible bacteria occurred. Dosages of 400 or 600 mg of ciprofloxacin every 12 h effectively reduced bacterial counts of one strain each of methicillin-susceptible or -resistant S. aureus, with no bacterial resistance detected at the end of experiment; in contrast, 200 mg every 12 h resulted in bacterial regrowth due to the selection of drug-resistant bacteria. These data show the need for high-dose intravenous ciprofloxacin, particularly with regimens producing high peak levels, for treatment of infections where selection for bacterial resistance is a clinical problem.
authors.affiliation: Antiinfective Pharmacology Research Unit, University of Rhode Island College of Pharmacy, Providence.
authors.forename: C R
authors.initials: CR
authors.lastname: Marchbanks
authors.forename: J R
authors.initials: JR
authors.lastname: McKiel
authors.forename: D H
authors.initials: DH
authors.lastname: Gilbert
authors.forename: N J
authors.initials: NJ
authors.lastname: Robillard
authors.forename: B
authors.initials: B
authors.lastname: Painter
authors.forename: S H
authors.initials: SH
authors.lastname: Zinner
authors.forename: M N
authors.initials: MN
authors.lastname: Dudley
mesh_terms: D002939:Ciprofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003470:Culture Media; D015342:DNA Probes; D004352:Drug Resistance, Microbial; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy*; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D003470:Culture Media; D015342:DNA Probes; D002939:Ciprofloxacin