The traditional approach to treating vancomycin-resistant enterococcus (VRE) urinary tract infections (UTIs) may be due for a significant shift, as mounting evidence supports the efficacy of aminopenicillin antibiotics even in cases of apparent resistance. Recent clinical studies demonstrate that drugs like ampicillin and amoxicillin achieve remarkably high concentrations in urine, effectively treating infections despite laboratory reports of resistance.
Clinical Efficacy Despite Resistance
Research shows that aminopenicillin therapy achieved an impressive 83.9% clinical cure rate in patients with VRE UTIs, compared to 73.3% in those treated with non-beta-lactam antibiotics. Notably, success rates remained high even when treating officially "resistant" strains, with 86% of patients with ampicillin-resistant isolates achieving clinical cure.
Understanding Drug Concentrations
The key to this apparent paradox lies in the pharmacokinetics of aminopenicillins. Studies have documented that a single 500mg dose of oral amoxicillin can achieve average urine concentrations of 1100 μg/mL over six hours. These concentrations far exceed the minimal inhibitory concentrations (MICs) typically seen in resistant strains, which range from 128 to 512 μg/mL.
Implications for Laboratory Testing
Current laboratory standards consider Enterococcus species resistant to ampicillin at MICs ≥ 16 μg/mL, regardless of infection site. However, this one-size-fits-all approach may be misleading for UTIs. Some hospitals have already adapted by discontinuing routine susceptibility testing for enterococcal urinary isolates, instead reporting them as universally susceptible to aminopenicillins.
Treatment Selection and Stewardship
When treating VRE UTIs, clinicians have typically turned to broad-spectrum alternatives such as linezolid, daptomycin, and fosfomycin. However, the demonstrated effectiveness of aminopenicillins suggests these more expensive, broader-spectrum options may often be unnecessary.
Impact on Antibiotic Stewardship
This understanding has significant implications for antibiotic stewardship programs. By preferentially using aminopenicillins for VRE UTIs, healthcare facilities can:
- Reduce unnecessary use of broad-spectrum antibiotics
- Lower treatment costs
- Preserve last-resort antibiotics for more serious infections
- Potentially improve patient outcomes
Future Directions
The development of urine-specific breakpoints for susceptibility testing could provide more reliable guidance for clinicians. In the meantime, healthcare institutions are encouraged to develop protocols that promote appropriate prescribing practices based on current evidence.
