A 68-year-old man is admitted to the hospital with a 3-week history of low-grade fevers, chills, and generalized fatigue. He recently underwent a cystoscopy for benign prostatic hyperplasia. On physical examination, his temperature is 38.2°C (100.8°F), and a new holosystolic murmur is heard at the cardiac apex. Blood cultures grow gram-positive cocci in pairs and short chains that are catalase-negative and grow in 6.5% NaCl broth. Transesophageal echocardiography reveals a 1.2-cm vegetation on the mitral valve.
The patient is started on continuous-infusion ampicillin and once-daily gentamicin to achieve synergistic bactericidal activity. Two days later, antimicrobial susceptibility testing results are reported as follows:
| Antimicrobial Agent | MIC (mcg/mL) | Interpretation |
|---|---|---|
| Ampicillin | 2 | Susceptible |
| Vancomycin | 1 | Susceptible |
| Gentamicin | >500 | High-level resistance |
| Streptomycin | 64 | Susceptible to synergy |
Given these results, gentamicin is discontinued, and ceftriaxone is added to the ampicillin regimen. Which of the following best describes the precise molecular mechanism responsible for the lack of ampicillin-gentamicin synergy in this patient's isolate?
- Enzymatic transfer of functional groups to the hydroxyl or amino moieties of the drugCevap
- BAmino acid substitution in a ribosomal protein altering the 30S subunit binding site
- CEnzymatic reprogramming of peptidoglycan precursors terminating in D-lactate
- DChromosomal mutation resulting in the overproduction of low-affinity transpeptidases
- EDownregulation of outer membrane porin channels preventing intracellular accumulation