A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections

Vancomycin is an antibiotic commonly used for the treatment of enterococcal infections. However, there is no clear correlation regarding of vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) ratio and clinical outcomes for the treatment of enterococcal infections. The aims of this study were to evaluate the relationship of vancomycin AUC/MIC ratio in patients with clinical outcomes and nephrotoxicity for patients with documented enterococcal infections. A Bayesian technique was used to calculate the average vancomycin AUC(0-24). The MIC was determined using the VITEK 2 automated microbiology system, and the average AUC(0-24)/MIC value was calculated for the first 72 h of therapy. All medical records of patients prescribed vancomycin with therapeutic drug monitoring were collected during January 2010-October 2020 at Chiang Mai University Hospital (CMUH). A retrospective single-center cohort of 312 participants were met the inclusion criteria. The results of this study showed that, a vancomycin AUC/MIC of >= 400 mg center dot h/L was associated with significant differences in clinical response compared to a vancomycin AUC/MIC of <400 mg center dot h/L (aHR: 0.50, 95% CI: 0.26-0.97; p = 0.042). Likewise, a vancomycin AUC/MIC of >= 400 mg center dot h/L was associated with significant differences in the microbiological response (aHR: 0.37, 95% CI: 0.14-0.94; p = 0.036), compared to a vancomycin AUC/MIC of <400 mg center dot h/L. However, nephrotoxicity in patients with a vancomycin AUC/MIC of >= 400 mg center dot h/L was higher than those with a vancomycin AUC/MIC of <400 mg center dot h/L (aHR: 3.96, 95% CI: 1.09-14.47; p = 0.037). Declining renal function may be a result of high vancomycin concentrations. In addition, declining renal function (e.g., failure to resolve the focus of infection, co-administration of other antibiotics) might result in higher AUC/MIC. We found a target vancomycin AUC/MIC of >= 400 mg center dot h/L and this AUC/MIC target value could be optimal for the use for monitoring treatment of enterococcal infections. Thus, vancomycin dosage must be adjusted to achieve the AUC/MIC target and closely monitored for renal function. These findings are not transferable to critically ill patients.

Automated summary

This study found that a vancomycin AUC/MIC of >=400 mg·h/L was associated with significant differences in clinical and microbiological responses, but also increased the risk of nephrotoxicity. Adjusting vancomycin dosage to achieve the optimal AUC/MIC target ≥400 mg·h/L is crucial for the treatment of enterococcal infections.