Predictive Value of Vancomycin AUC24/MIC Ratio for 30-day Mortality in Patients with Severe or Complicated Methicillin-Resistant Staphylococcus aureus Infections: A Multicenter Retrospective Study

Abstract

Background: Although vancomycin is typically employed against methicillin-resistant Staphylococcus aureus (MRSA) infections, the optimal ratio of 24-h area under the concentration-time curve to minimum inhibitory concentration (AUC₂₄/MIC) for severe or complicated infections lacks clear guideline recommendations. This study aimed to determine the target AUC₂₄/MIC ratio associated with treatment outcomes of infections treated with vancomycin.

Methods: This retrospective multicenter cohort study included adult patients receiving ≥ 5 days of vancomycin for severe/complicated MRSA infections (e.g., osteoarticular, pulmonary, endocarditis, etc.) between January 2018 and December 2023. The primary outcome was 30-day mortality, with secondary outcomes including clinical success, microbiological eradication, and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC₂₄/MIC cutoff for 30-day mortality. Multivariate regression analysis was used to determine association between AUC₂₄/MIC and outcomes.

Results: This study included 82 patients. ROC identified a target AUC₂₄/MIC of ≥ 505 for 30-day mortality. The overall 30-day mortality rate (22.0%) was significantly higher for below average AUC₂₄/MIC cutoff (34.1%) than for above AUC₂₄/MIC cutoff group (9.8%). Multivariate analysis confirmed AUC₂₄/MIC of < 505 as an independent predictor (adjusted odds ratio, 5.001; 95% confidence interval, 1.335-18.75). The clinical success rate differed significantly between below- and above-cutoff groups, whereas microbiological eradication tended to favor the above-cutoff group. The nephrotoxicity rates were comparable between groups.

Conclusions: In treating severe/complicated MRSA infections, vancomycin AUC₂₄/MIC ratio ≥ 505 was independently associated with favorable 30-day mortality. Given the retrospective nature of this study, further prospective studies are essential to confirm the reliability of the target AUC₂₄/MIC ratios.

Keywords: AUC24/MIC; complicated infection; methicillin-resistant staphylococcus aureus; therapeutic drug monitoring; vancomycin.