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Nitroimidazoles: in vitro activity and efficacy in anaerobic infections.

Nitroimidazoles, including metronidazole, tinidazole and ornidazole, are low molecular weight antimicrobial compounds with excellent activity against anaerobic microorganisms. These compounds are usually bactericidal at low concentrations and their spectrum of activity encompasses almost all the anaerobic bacteria and some capnophylic organisms. The few anaerobic bacteria known to be resistant to the nitroimidazoles include occasional anaerobic cocci, some nonsporing gram positive bacilli and Propionibacterium. Nitroimidazoles are the most active antimicrobial agents known against Bacteroides fragilis, the most resistant of anaerobic bacteria. Kill-curve studies demonstrate that there is a 2 to 5 log decrease in the number of colony forming units with Bacteroides fragilis and clostridium perfringens within one hour. The killing is unaffected by inoculum, growth rate or components of the medium. However, a metronidazole resistant isolate of B. fragilis has been shown to have decreased ability to take up 14C-metronidazole as well as lessened ability to reduce metronidazole. This is associated with a decrease in the nitroreductase activity. The in vitro observations have also been demonstrated in vivo. Clinical studies have shown nitroimidazoles to be efficacious in the therapy of a variety of anaerobic infections including non-traumatic brain abscess, intraabdominal abscesses, pelvic suppuration and necrotizing soft tissue infections. However, there have been disappointing results in the therapy of anaerobic pleuropulmonary infections, with a number of superinfections caused by aerobic bacteria.