DOSE-RANGING AND FRACTIONATION OF INTRAVENOUS CIPROFLOXACIN AGAINST PSEUDOMONAS-AERUGINOSA AND STAPHYLOCOCCUS-AUREUS IN AN IN-VITRO MODEL OF INFECTION

The effect of dose or dose interval on the pharmacodynamics of simulat ed high-dose intravenous ciprofloxacin therapy on infection due to Pse udomonas aeruginosa and Staphylococcus aureus was studied in an in vit ro hollow-fiber model of infection. Simulated doses of 1,200 mg of cip rofloxacin per day as either 400 mg every 8 h or 600 mg every 12 h aga inst P. aeruginosa resulted in selection of ciprofloxacin-resistant ba cteria. The results with one test strain that was isolated from a pati ent prior to administration of intravenous ciprofloxacin demonstrated selection of a gyrA mutant in the model, as had occurred in vivo. A si ngle 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 effecti vely reduced bacterial counts of one strain each of methicillin-suscep tible or -resistant S. aureus, with no bacterial resistance detected a t the end of experiment; in contrast, 200 mg every 12 h resulted in ba cterial regrowth due to the selection of drug-resistant bacteria. Thes e data show the need for high-dose intravenous ciprofloxacin, particul arly with regimens producing high peak levels, for treatment of infect ions where selection for bacterial resistance is a clinical problem.