A patient with a serious Enterococcus faecalis endocarditis fails vancomycin monotherapy. Adding ampicillin is considered. The basis of synergy between ampicillin and vancomycin against enterococci is:

• A Vancomycin inhibits efflux pumps, increasing intracellular ampicillin concentration
• B Both drugs together overcome the intrinsic low-level aminoglycoside resistance of enterococci
• C Synergy is pharmacokinetic; the combination achieves higher serum levels than either drug alone
• D Ampicillin binds PBP4/5 rendering peptidoglycan accessible for vancomycin's lipid II target ✓

Explanation

Enterococci have intrinsic tolerance to cell wall-active agents individually. Ampicillin binds PBP4/5 and partially disrupts the cell wall, facilitating vancomycin's access to its lipid II (undecaprenyl-pyrophosphate-MurNAc-pentapeptide) target in the inner leaflet. This pharmacodynamic synergy improves bactericidal activity and is the mechanistic basis for combining beta-lactams with glycopeptides in serious enterococcal infections when aminoglycoside synergy cannot be used.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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