Metronidazole: in vitro activity, pharmacology and efficacy in anaerobic bacterial infections

Metronidazole is a 5-nitroimidazole that has selective activity against anaerobic microorganisms, including bacteria and protozoa. Intravenous metronidazole has recently been approved by the U.S. Food and Drug Administration for the treatment of serious anaerobic bacterial infections. It is usually bactericidal at low concentrations, and its spectrum of activity encompasses almost all anaerobic bacteria and some capnophilic organisms. Anaerobic bacteria known to be resistant to metronidazole include occasional anaerobic cocci, some nonsporulating gram-positive bacilli and propionibacterium. Metronidazole is the most active antimicrobial agent 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 of B. fragilis and Clostridium perfringens within one hour. The only well documented metronidazole-resistant strain is a B. fragilis isolated from the normal flora of a patient on long-term metronidazole therapy for Crohn's Disease. Metronidazole resistance in Trichomonas vaginalis has recently been described in a few strains that are able to survive at increased oxygen tensions. Metronidazole has been shown to be efficacious in certain protozoal infections including trichomonal vaginitis, extraintestinal amebiasis, and giardiasis. Clinical studies have shown metronidazole to be efficacious in the therapy of a variety of anaerobic infections, including non-traumatic brain abscesses, intraabdominal sepsis, pelvic suppuration and necrotizing soft tissue infections. There have been disappointing results in the therapy of anaerobic pleuropulmonary infections with a number of superinfections caused by aerobic bacteria. Since metronidazole lacks any activity against aerobic bacteria, it must be combined with other agents, usually aminoglycosides, in the treatment of mixed infections involving anaerobic and aerobic bacteria.