EVALUATION OF ACTIVITY OF TEMAFLOXACIN AGAINST BACTEROIDES-FRAGILIS BY AN IN-VITRO PHARMACODYNAMIC SYSTEM

An in vitro pharmacodynamic system has been successfully adapted to si mulate in vivo antimicrobial pharmacokinetics under anaerobic conditio ns. This system was used to perform time-kill kinetic studies which we re designed to compare the activity of temafloxacin to ciprofloxacin a nd cefotetan against two strains of Bacteroides fragilis (ATCC 25285 a nd ATCC 23745). All experiments were performed as single-dose, 24-h, d uplicate runs. Starting bacterial inocula of 10(7) CFU/ml were exposed to starting antimicrobial concentrations of 5 mug of temafloxacin per ml, 5 mug of ciprofloxacin per ml, and 100 mug of cefotetan per ml. T erminal half-lives of 8, 4, and 4 h were simulated for each antimicrob ial agent. Temafloxacin was rapidly bactericidal against B. fragilis. Ciprofloxacin was not bactericidal (<3 log10 unit decline in bacterial numbers) to either strain of B. fragilis. Cefotetan was bactericidal (greater-than-or-equal-to 3 log10 unit decline in bacterial numbers) t o each strain but killed at a slower rate than temafloxacin. Times to 3 log10 unit declines of strain ATCC 25285 were 2, 4, and >24 h, where as those of strain ATCC 23745 were 4, 4, and >24 h for temafloxacin, c efotetan, and ciprofloxacin, respectively. Total logarithmic declines of strain ATCC 25285 were >4.5, >4.5, and 2.9 log10 CFU/ml, whereas th ose of strain ATCC 23745 were 4. 1, >4.5, and 1.2 log10 CFU/ml for eac h drug, respectively. These and other studies demonstrated that temafl oxacin showed potential as an agent that could have been further devel oped for use in the treatment of anaerobic infections. However, the dr ug was removed from the market by its manufacturer because of toxicity issues. Although the release of newer fluoroquinolones that possess s ignificant activity against anaerobic bacteria does not appear imminen t, the time-kill studies performed in this study demonstrate that furt her research is warranted in the development of fluoroquinolones which possess significant antianaerobic activity.