Metronidazole is active against anaerobic bacteria and protozoa but not against aerobic organisms. The mechanism that limits its activity to anaerobes is:

• A Metronidazole is only absorbed by the specific porins present on anaerobic bacterial outer membranes
• B Metronidazole requires reductive activation by low redox-potential electron carriers (ferredoxin) present only in anaerobic/microaerophilic organisms to form cytotoxic nitroso free radicals ✓
• C Oxygen in aerobic cells inhibits metronidazole transport by upregulating efflux pumps
• D Metronidazole is degraded by aerobic bacteria via flavin-dependent oxidoreductases before it can act

Explanation

Metronidazole is a prodrug that must be reduced to its active nitro radical anion form. This activation requires acceptance of electrons from low-potential electron donors (ferredoxin and PFOR — pyruvate:ferredoxin oxidoreductase), which are present in anaerobic organisms and microaerophiles but absent in aerobic bacteria. In aerobic organisms, oxygen rapidly re-oxidises the nitro group before cytotoxic radicals can accumulate. This strict redox-dependent selectivity confines its spectrum to anaerobes and protozoa (Trichomonas, Giardia, Entamoeba).

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

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