Abstract: TH-PO064
Using Kinetic eGFR for Vancomycin Dosing When Renal Clearance Is Acutely Changing: A Simulation Study
Session Information
- AKI: Liver Disease, Nephrotoxicity, Novel Therapeutics
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Bairy, Manohar, Tan Tock Seng Hospital, Singapore, Singapore
- Khoo, Benjamin Zhi En, Tan Tock Seng Hospital, Singapore, Singapore
- Tan, Sock Hoon, Tan Tock Seng Hospital, Singapore, Singapore
- Peh, Leticia Xyn Yen, Tan Tock Seng Hospital, Singapore, Singapore
- Lim, Siow Yu, Tan Tock Seng Hospital, Singapore, Singapore
- Shen Hui, Chuang, Tan Tock Seng Hospital, Singapore, Singapore
Background
Achieving target vancomycin trough (VT) levels in acutely ill patients is a challenge. Using Cockcroft Gault estimated creatinine clearance (CGeCrCl) for drug dosing lacks validation when the creatinine level is unsteady. In this cohort of hospitalised patients treated with CGeCrCl based vancomycin dosing, we used Kinetic estimated GFR (KeGFR) and MDRD eGFR to predict VT levels and to simulate vancomycin dosing frequencies and explored the likelihood of achieving target VT levels.
Methods
Among 111 methicillin-resistant Staphylococcus aureus bacteremic patients treated with intravenous vancomycin who had creatinine levels varying by > 5% during treatment, a study subgroup (SSG) consisted of 38 patients who had VT levels checked after the first (loading) dose and before the second dose.Predicted VT using CGeCrCl, KeGFR and MDRD eGFR calculated using population pharmacokinetic equations and compared to the true (observed) VT using Bland Altman (BA) plots for agreement in the SSG. The dosing frequency was simulated using KeGFR and MDRD eGFRs based on the hospital vancomycin dosing protocol and the likelihood of achieving the target VT (10-20mg/L) was estimated for each method.
Results
VT levels of 41 patients (37%) were <10mg/L. In the SSG, CGeCrCl was 23.3ml/min (IQR 14.3,30.3), 34% had acute kidney injury (AKI) or were recovering from AKI and 79% had at least 5% variation in 2 consecutive creatinine levels including the level used to determine the vancomycin dosing frequency. 17 (45%) patients had subtherapeutic VT levels in the SSG. KeGFR-predicted VT showed the best agreement with true VT with a mean difference of -0.128 using the BA method. The mean difference was +3.81 for CGeCrCl predicted VT and +0.78 for MDRD predicted VT. In the dose frequency simulation model, 11 of the 17 patients with VT <10mg/L were likely to achieve the target VT when KeGFR is used, compared to 10 patients when MDRD eGFR is used and 2 patients with target VT levels were likely to attain subtherapeutic levels when MDRDeGFR is used .
Conclusion
KeGFR based vancomycin dosing is more likely to achieve target VT levels in comparison to CGeCrCl and MDRD eGFR based dosing in patients with fluctuating creatinine levels. KeGFR based vancomycin dosing will need to be further validated prospectively in a randomised clinical trial.