Pharmacokinetic/pharmacodynamic analysis of vancomycin in patients with Enterococcus faecium bacteraemia: a retrospective cohort study.

Objectives: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus. However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia.

Methods: Between January 2014 and December 2021 we performed a retrospective cohort study of patients with E. faecium bacteraemia treated with vancomycin. Patients who received renal replacement therapy or had chronic kidney disease were excluded. Clinical failure, the primary outcome, was defined as a composite of 30-day all-cause mortality, vancomycin-susceptible infection requiring change of treatment, and/or recurrence. AUC₂₄ was estimated using a Bayesian estimation approach based on an individual vancomycin trough concentration. The MIC for vancomycin was determined using a standardised agar dilution method. Additionally, classification was used to identify the vancomycin AUC₂₄/MIC ratio associated with clinical failure.

Results: Of the 151 patients identified, 69 were enrolled. All MICs of vancomycin for E. faecium were ≤1.0 µg/mL. The AUC₂₄ and AUC₂₄/MIC ratio were not significantly different between the clinical failure group and the clinical success group (432±123 µg/mL/hour vs 488±92 µg/mL/hour; p=0.075). However, 7 of 12 patients (58.3%) in the clinical failure group and 49 of 57 patients (86.0%) in the clinical success group had a vancomycin AUC₂₄/MIC ratio ≥389 (p=0.041). No significant association between trough concentration or AUC₂₄ ≥600 µg/mL×hour and acute kidney injury was observed (p=0.365 and p=0.487, respectively).

Conclusion: The AUC₂₄/MIC ratio is associated with the clinical outcome of vancomycin administration in E. faecium bacteraemia. In Japan, where vancomycin-resistant enterococcal infection is rare, empirical therapy with a target AUC₂₄ ≥389 should be recommended.