A 32-year-old woman with Clostridium difficile colitis is prescribed metronidazole. The drug's bactericidal activity depends on:

• A The drug being oxidized by NADH dehydrogenase in aerobic organisms
• B Inhibition of clostridial cell wall peptidoglycan transpeptidase
• C Binding to ergosterol in the clostridial membrane
• D Reduction of its nitro group by anaerobic ferredoxin, forming toxic radicals that damage DNA ✓

Explanation

Metronidazole enters anaerobic bacteria and protozoa, where its nitro group is reduced by electron transport proteins (ferredoxin-like systems) to form cytotoxic reactive intermediates that cause strand breaks in DNA. Because this reductive activation requires the low redox potential environment of anaerobes/microaerophiles, the drug is selectively toxic to anaerobic organisms and inactive in aerobic conditions. This explains its spectrum limited to anaerobic bacteria and protozoa such as Giardia, Trichomonas, and Entamoeba.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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