Association Between Follow-Up Therapeutic Drug Monitoring and Vancomycin-Induced Nephrotoxicity: A Claims Database...

In vancomycin treatment, follow-up therapeutic drug monitoring (TDM) within 1 week after the initial TDM is recommended in patients with dose change after the initial TDM or high risk of vancomycin-induced nephrotoxicity (VIN); however, the effectiveness of follow-up TDM implementation remains unclear. This study aimed to delineate outcomes of follow-up TDM after the initial assessment under real-world conditions in Japan and clarify its association with VIN.

Retrospective data analysis was conducted using a Japanese health insurance claims database. Approval was granted by the Ethics Committee of Osaka Medical and Pharmaceutical University (protocol number: 2022-105). Adult patients who received intravenous vancomycin, excluding those without a dose change after the initial TDM and without risk of VIN between January 2020 and December 2021, were included. Follow-up TDM was defined as conducting TDM within 1 week after the initial assessment. The association between performing follow-up TDM and the occurrence of VIN was assessed in patients with dose change after the initial TDM or high risk of VIN.

Among 492 patients who underwent the initial TDM, 403 (81.9%) had follow-up TDM performed. Cox proportional hazards model analysis revealed that follow-up TDM was associated with a lower occurrence of VIN after adjustment for estimated glomerular filtration rate <30 mL/min/1.73 m², concomitant nephrotoxic drugs, vasopressors, loop diuretics, initial vancomycin trough concentration >15 mg/L (hazard ratio 0.47; 95% confidence interval (CI) 0.25-0.86, p = 0.015). In a sensitivity analysis using inverse probability of treatment weighting, which additionally adjusted for institutional characteristics and baseline clinical risk factors, the association was attenuated and did not reach statistical significance (hazard ratio 0.62; 95% CI 0.31-1.23; p = 0.167), with residual imbalance remaining for some covariates after weighting. An exploratory receiver operating characteristic (ROC) analysis suggested a TDM frequency of 1.009 per week with a modest area under the ROC curve of 0.673 (95% CI 0.597-0.749), sensitivity of 0.618, and specificity of 0.661 (p < 0.001).

This study found that follow-up TDM was associated with a lower occurrence of VIN, supporting guidelines recommending follow-up TDM in vancomycin therapy. Health providers should consider conducting follow-up TDM to potentially lower the occurrence of VIN, although further prospective studies are warranted to clarify its independent effect.