Dose ranging and fractionation of intravenous ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of infection

Antimicrob Agents Chemother. 1993 Sep;37(9):1756-63. doi: 10.1128/aac.37.9.1756.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / therapeutic use*
  • Culture Media
  • DNA Probes
  • Drug Resistance, Microbial
  • Humans
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Pseudomonas Infections / drug therapy*
  • Staphylococcal Infections / drug therapy*
  • Time Factors

Substances

  • Culture Media
  • DNA Probes
  • Ciprofloxacin