PK/PD study of vancomycin in enterococcal infections: efficacy and safety assessment under the guidance of TDM.

内容摘要

Vancomycin is widely utilized in the treatment of Enterococcus infections; however, the optimal pharmacokinetic/pharmacodynamic (PK/PD) targets, specifically the 24 h area under the concentration-time curve at steady state (AUC24h), and trough concentration (Cmin), remain undefined. This study aims to examine the relationship between vancomycin exposure and clinical outcomes in Enterococcus infections while establishing PK/PD target values. A retrospective observational analysis was performed on 154 hospitalized patients diagnosed with Enterococcus infections treated with vancomycin. Clinical efficacy, acute kidney injury (AKI), 30-day all-cause mortality, and 14-day bacterial clearance were evaluated. Multivariate logistic regression, Cox regression, and receiver operating characteristic curve analysis were employed to identify independent predictors and determine optimal exposure thresholds. The clinical efficacy rate was 72.1%, with an AKI incidence of 20.8%, a 30-day all-cause mortality rate of 14.3%, and a 14-day bacterial clearance rate of 77.9%. Multivariate analysis identified C-reactive protein >100 mg/L, the presence of bloodstream infections, and an AUC24h > 380.00 mg·h/L as independent predictors of clinical efficacy. AUC24h > 540.00 mg·h/L and the Sequential Organ Failure Assessment (SOFA) score were independently associated with the occurrence of AKI. Independent risk factors for 30-day mortality included the SOFA score, surgery, age >60 years, and AUC24h > 580.00 mg·h/L. Intra-abdominal infections and Cmin > 11.00 mg/L were identified as independent predictors of 14-day bacterial clearance. For Enterococcus spp., the recommended therapeutic target ranges are AUC24h 370-540 mg·h/L and Cmin 10-14 mg/L. For Enterococcus faecium, the optimal therapeutic window is AUC24h 425-560 mg·h/L and Cmin 10-18 mg/L. Optimized vancomycin exposure targets vary by Enterococcus species. A stratified PK/PD-guided approach-utilizing a broader initial target when the species is unknown and a refined target range for confirmed E. faecium-may enhance therapeutic efficacy while minimizing nephrotoxicity. These findings provide evidence supporting individualized vancomycin dosing in the treatment of enterococcal infections.IMPORTANCEEnterococcus infections pose a significant treatment challenge, as optimal vancomycin dosing remains poorly defined. This study establishes evidence-based, species-specific exposure targets. For Enterococcus spp., the recommended targets are AUC24h 370-540 mg·h/L and Cmin 10-14 mg/L; for Enterococcus faecium, a refined window of AUC24h 425-560 mg·h/L and Cmin 10-18 mg/L is proposed. These findings have important implications for individualized dosing and patient outcomes in Enterococcus infections.