Why metronidazole is active against both bacteria and parasites.

Metronidazole is one of the rare examples of a drug developed against a parasite which has since gained broad use as an antibacterial agent (24). Briefly, at Rhone-Poulenc labs in France, extracts of Streptomyces spp. were screened for activity against Trichomonas vaginalis, a cause of vaginal itching. Azomycin, a nitroimidazole, was identified, and metronidazole, a synthetic derivative, was used to treat chronic trichomonad infections, beginning in 1959 (66). Metronidazole was shown to be efficacious against Entamoeba histolytica, the cause of amebic dysentery and liver abscess, in 1966 (67). Giardia lamblia (also known as G. duodenalis) was treated with metronidazole after this luminal parasite was recognized as a cause of malabsorption and epigastric pain in the 1970s (102). The antibacterial activity of metronidazole was discovered by accident in 1962 when metronidazole cured a patient of both trichomonad vaginitis and bacterial gingivitis (78). However, it was not until the 1970s that metronidazole was popularized for treatment of infections caused by gram-negative anaerobes such as bacteroides or gram-positive anaerobes such as clostridia (24, 48). Presently, metronidazole, which is inexpensive, has good tissue penetration, and produces relatively mild side effects, is on the formulary at most hospitals for prophylaxis against anaerobic infection after bowel surgery, for treatment of wound abscess, and for treatment of antibioticassociated colitis caused by Clostridium difficile (85, 94). Metronidazole is an important part of combination therapy against Helicobacter pylori, a major cause of gastritis and a risk factor for stomach cancer (21, 57).