Optimizing vancomycin therapy: the critical role of dosing frequency, AUC monitoring and gender: a retrospective cohort study
TL;DR
Traditional PK/PD targets (Ctrough and AUC/MIC) did not correlate with clinical efficacy in this real-world setting, and AUC was a better predictor of nephrotoxicity than Ctrough, and female gender was an independent risk factor for vancomycin-associated anemia.
Abstract
Background Optimizing vancomycin therapy requires balancing efficacy and toxicity. Although therapeutic drug monitoring (TDM) guided by area-under-the-curve (AUC) measurements is now recommended, the effect of dosing frequency and patient-specific factors remain underexplored. This study examined the relationships of dosing frequency, pharmacokinetic/pharmacodynamic (PK/PD) parameters, clinical efficacy, and toxicities in patients receiving different vancomycin regimens. Methods This retrospective cohort study analyzed 193 vancomycin dosing regimens in 148 adult patients who were treated at a tertiary teaching hospital in China between January 2013 and March 2021, 175 of which were guided by TDM. The full TDM-guided cohort (n = 175) was used for analysis of safety and PK; clinical efficacy was assessed in 59 culture-confirmed cases; and the association of PK/PD parameters with efficacy was examined in the 26 patients who received a 1 g q12 h regimen for staphylococcal infections. Results In the subset of 26 patients with staphylococcal infections who received the 1 g q12 h regimen, clinical success was not significantly associated with Ctrough, AUC, or AUC/minimum inhibitory concentration (AUC/MIC). For the entire TDM-guided cohort, dosing frequency was a significant and independent determinant of Ctrough (P = 0.031), in that more frequent dosing led to higher Ctrough values without altering total daily AUC. Receiver operating characteristic (ROC) analysis indicated that AUC was a better predictor of nephrotoxicity (AUROC = 0.754) than Ctrough (AUROC = 0.659). Multivariate analysis confirmed that pre-treatment creatinine clearance was the primary predictor of post-treatment renal function. Female gender was an independent risk factor for post-treatment anemia (P = 0.002). Conclusion Among the 26 patients with staphylococcal infections receiving the 1 g q12 h regimen, traditional PK/PD targets (Ctrough and AUC/MIC) did not correlate with clinical efficacy in this real-world setting. AUC was a better predictor of nephrotoxicity than Ctrough, and female gender was an independent risk factor for vancomycin-associated anemia.