A 60-year-old man on hemodialysis is diagnosed with enterococcal endocarditis. Culture shows Enterococcus faecalis susceptible to ampicillin but resistant to all aminoglycosides (high-level aminoglycoside resistance, HLAR). What synergistic combination is appropriate?

• A Ampicillin + vancomycin
• B Vancomycin + daptomycin
• C Ampicillin + ceftriaxone (double beta-lactam regimen) ✓
• D Linezolid + rifampicin

Explanation

In Enterococcus faecalis endocarditis, synergistic bactericidal killing is essential because enterococci are intrinsically tolerant to cell-wall active agents alone. The classical synergy was ampicillin + aminoglycoside; however, high-level aminoglycoside resistance (HLAR) eliminates this synergy. In HLAR strains, the dual beta-lactam combination of ampicillin + ceftriaxone achieves synergy through saturation of different penicillin-binding proteins (PBP4 by ampicillin; PBP5 and PBP2b by ceftriaxone), leading to bactericidal activity. This is now recommended by IDSA/AHA guidelines for HLAR E. faecalis endocarditis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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