An in vitro pharmacodynamic system has been successfully adapted to simulate in vivo antimicrobial pharmacokinetics under anaerobic conditions. This system was used to perform time-kill kinetic studies which were designed to compare the activity of
temafloxacin to
ciprofloxacin and
cefotetan against two strains of Bacteroides fragilis (ATCC 25285 and ATCC 23745). All experiments were performed as single-dose, 24-h, duplicate runs. Starting bacterial inocula of 10(7) CFU/ml were exposed to starting antimicrobial concentrations of 5 micrograms of
temafloxacin per ml, 5 micrograms of
ciprofloxacin per ml, and 100 micrograms of
cefotetan per ml. Terminal half-lives of 8, 4, and 4 h were simulated for each
antimicrobial 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 (> or = 3 log10 unit decline in bacterial numbers) to 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, whereas those of strain ATCC 23745 were 4, 4, and > 24 h for
temafloxacin,
cefotetan, and
ciprofloxacin, respectively. Total logarithmic declines of strain ATCC 25285 were > 4.5, > 4.5, and 2.9 log10 CFU/ml, whereas those of strain ATCC 23745 were 4.1, > 4.5, and 1.2 log10 CFU/ml for each
drug, respectively. These and other studies demonstrated that
temafloxacin showed potential as an agent that could have been further developed for use in the treatment of anaerobic
infections. However, the
drug was removed from the market by its manufacturer because of toxicity issues. Although the release of newer
fluoroquinolones that possess significant activity against anaerobic bacteria does not appear imminent, the time-kill studies performed in this study demonstrate that further research is warranted in the development of
fluoroquinolones which possess significant antianaerobic activity.