Date of Original Version
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.
Marchbanks, C. R., McKiel, J. R., Gilbert, D. H., Robillard, N. J., Painter, B., Zinner, S. H., & Dudley, M. N. (1993). Dose Ranging and Fractionation of Intravenous Ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus in an In Vitro Model of Infection. Antimicrob. Agents Chemother., 37(9), 1756-1763. doi: 10.1128/AAC.37.9.1756.
Available at: http://dx.doi.org/10.1128/AAC.37.9.1756