Metronidazole is active against anaerobes and protozoa but not aerobes. The reason for this selective activity is:

• A Aerobes lack the nitroreductase enzyme necessary to activate the prodrug
• B Aerobes have high levels of superoxide dismutase that inactivate the reduced metabolite
• C Metronidazole specifically inhibits anaerobic glycolysis, which aerobes do not rely upon
• D Metronidazole is selectively taken up by obligate anaerobes and protozoa; the drug is reduced by ferredoxin or pyruvate:ferredoxin oxidoreductase (PFOR) in low-redox environments to form cytotoxic nitroso radicals that damage DNA ✓

Explanation

Metronidazole is a prodrug that is reductively activated by low intracellular redox potential found only in strict anaerobes and certain protozoa (e.g., Trichomonas, Giardia, Entamoeba). Ferredoxin or pyruvate:ferredoxin oxidoreductase (PFOR) transfer electrons to the nitro group, forming reactive nitroimidazole radicals that cause strand breaks in DNA. Aerobes maintain a high intracellular redox potential (high [O2]), preventing this reduction step — the drug passes through them unchanged. This mechanism also underlies resistance via nitroreductase mutation or PFOR loss.

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

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