sitafloxacin and temafloxacin

The currently available fluoroquinolones have modest activity against anaerobes. Newer fluoroquinolones with increased in vitro activity against anaerobes are under development and include levofloxacin, clinafloxacin, sparfloxacin, trovafloxacin, grepafloxacin, and DU-6859a. Side effects of the quinolones have varied according to the specific compounds and include central nervous system stimulation, gastrointestinal disturbances, vasculitis, and photosensitization. Monitoring for toxicity is incompletely reliable in identifying all potential serious side effects such as the "temafloxacin syndrome." Other fluoroquinolones may produce this syndrome rarely or not at all. In this paper, I review limited published studies on the use of these agents for skin and skin-structure infections and gynecologic infections. Studies in progress are noted, and when available, in vitro data on the efficacy of these agents against bacterial isolates from specific sources are reviewed and evaluated in terms of potential clinical utility.

Topics: Anti-Infective Agents; Bacteria, Anaerobic; Bacterial Infections; Fluoroquinolones; Humans; Levofloxacin; Naphthyridines; Ofloxacin; Piperazines; Quinolones; Safety; Syndrome

A panel of 266 clinically isolated Gram-positive cocci and Gram-negative bacilli with varying levels of resistance to ciprofloxacin were analysed for susceptibility to Du-6859a, ciprofloxacin, ofloxacin, temafloxacin and nalidixic acid. Staphylococci were divided into ciprofloxacin-susceptible, moderately resistant and highly resistant subgroups. Du-6859a was the most potent quinolone against all taxa. As ciprofloxacin resistance increased to high levels, MICs of all quinolones increased but Du-6859a MICs increased least, and ciprofloxacin MICs increased most. Less susceptible single-step mutants were selected from 80% of 15 representative clinical isolates exposed to ciprofloxacin, 71% of isolates exposed to temafloxacin, 67% of isolates exposed to Du-6859a and 53% of isolates exposed to ofloxacin. Du-6859a inhibited more mutants (67%) at a concentration of 1 mg/L than did the other quinolones (26-43%) at their susceptible breakpoints. Du-6859a was the most rapidly bactericidal quinolone in time-kill studies with Enterococcus faecalis and Enterococcus faecium. This study indicated that Du-6859a is more potent than the comparator quinolones, is less affected by the mechanisms responsible for high-level quinolone resistance and may be less likely to select resistant mutants if it has a susceptible breakpoint of 1 mg/L.

Topics: Anti-Infective Agents; Ciprofloxacin; Drug Resistance, Microbial; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Microbial Sensitivity Tests; Mutation; Nalidixic Acid; Ofloxacin; Quinolones

A new method of assessing the bactericidal activity of quinolones and other antibacterial agents, known as the bactericidal index or BI, is introduced and discussed. The BI represents total bacterial kill over a drug concentration range limited to levels achievable in vivo. This method allows the bactericidal activity of drugs to be readily compared. Calculation of BI produces a single value per bacterial strain/antibacterial agent combination that represents overall bactericidal activity at clinically relevant concentrations. As an example, the bactericidal activities of quinolones against Enterococcus faecalis are compared.

Topics: Anti-Infective Agents; Ciprofloxacin; Enterococcus faecalis; Fluoroquinolones; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Quinolones