New Drug Evaluations: Metronidazole (Flagyl IV®, Searle)

Metronidazole is a narrow spectrum antibiotic with undoubted efficacy against common anaerobic bacteria; resistance is unusual. Therapeutic concentrations of the drug are attained throughout most body compartments after either oral or intravenous administration. The limited side effects of metronidazole are generally tolerable, transient, or reversible. Clinically, metronidazole is as effective as clindamycin and probably chloramphenicol against anaerobes. It has a definite advantage over clindamycin in CNS infections since clindamycin does not penetrate the CSF well. Metronidazole has no irreversible hematologic toxicities, nor has pseudomembranous colitis been definitely attributed to intravenous use of the drug. Metronidazole may replace chloramphenicol for use in anaerobic infections since it lacks the predictable hematologic toxicity of the latter drug. It should also be useful in patients who fail to respond to clindamycin or who develop pseudomembranous colitis while receiving clindamycin. Problems with metronidazole include a complicated preparation procedure, and the high cost of the drug. The single major drawback to the use of metronidazole is uncertainty about its carcinogenic potential in humans. Metronidazole is carcinogenic in animals and mutagenic in vitro, but has not increased the incidence of cancer in humans followed for relatively short periods. Thus, the risk appears to be small. Still, the question will not be resolved for years because of the long latency periods involved in carcinogenesis. Until that time, metronidazole should be used conservatively.