A patient receiving ceftriaxone for community-acquired meningitis develops hypoprothrombinemia and bleeding. This adverse effect is attributed to:

• A Direct inhibition of hepatic vitamin K epoxide reductase by ceftriaxone
• B Ceftriaxone displacing warfarin from plasma protein binding sites
• C The N-methylthiotetrazole (NMTT) side chain inhibiting vitamin K-dependent clotting factor synthesis ✓
• D Ceftriaxone suppressing intestinal bacteria that produce menaquinone (vitamin K2)

Explanation

Cephalosporins with an N-methylthiotetrazole (NMTT) side chain at position 3 (such as cefamandole, cefoperazone, moxalactam) inhibit gamma-carboxylation of vitamin K-dependent clotting factors (II, VII, IX, X) by interfering with vitamin K recycling, leading to hypoprothrombinemia and a disulfiram-like reaction with alcohol. Ceftriaxone does not have the NMTT group; however, cefoperazone is the classic example. This question tests knowledge that bleeding tendency with certain cephalosporins is a class-specific structural effect.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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