Pharmacokinetic/Pharmacodynamic Determinants of Vancomycin Efficacy in Enterococcal Bacteremia

Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01602-17. doi: 10.1128/AAC.01602-17. Print 2018 Mar.


While pharmacokinetic-pharmacodynamic targets for vancomycin therapy are recognized for invasive methicillin-resistant Staphylococcus aureus infections, scant data are available to guide therapy for other Gram-positive infections. A retrospective single-center cohort of patients with Enterococcus bacteremia hospitalized between 1 January 2009 and 31 May 2015 were studied. The average vancomycin AUC0-24 was computed using a Bayesian approach. The MIC was determined by gradient diffusion (Etest; bioMérieux), and the average AUC0-24/MIC value over the initial 72 h of therapy was calculated. We assessed 30-day all-cause mortality as the primary outcome. Classification and regression tree analysis (CART) was used to identify the vancomycin AUC0-24/MIC value associated with 30-day mortality. Fifty-seven patients with enterococcal bacteremia (32 E. faecium, 21 E. faecalis, and 4 other Enterococcus spp.) were studied. The median vancomycin MIC was 0.75 mg/liter (range, 0.38 to 3 mg/liter). All-cause 30-day mortality occurred in 10 of 57 patients (17.5%). A CART-derived vancomycin AUC/MICEtest value of ≥389 was associated with reduced mortality (P = 0.017); failure to achieve this independently predicted 30-day mortality (odds ratio, 6.83 [95% confidence interval = 1.51 to 30.84]; P = 0.01). We found that a vancomycin AUC/MICEtest value of ≥389 achieved within 72 h was associated with reduced mortality. Larger, prospective studies are warranted to verify the vancomycin pharmacodynamic targets associated with maximal clinical outcomes and acceptable safety.

Keywords: AUC/MIC; Enterococcus; bacteremia; pharmacodynamics; pharmacokinetics; vancomycin.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology*
  • Bayes Theorem
  • Enterococcus / drug effects*
  • Enterococcus / pathogenicity*
  • Female
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Retrospective Studies
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use*


  • Vancomycin