Prospective Analysis of Various Dosing Methods for Aminoglycosides and Vancomycin Therapy in Chronic Spinal Cord Injury Patients

Abstract

Background/Aim: Several methods have been proposed for the better estimation of creatinine clearance (CL_CR) in spinal cord injury (SCI); however, there is no standard method to date. In 2011, Lee-Dang derived an equation to predict CL_CR more accurately, although it was limited by problems inherent in any retrospective study of previously collected data. Thus, a prospective investigation was conducted to evaluate the feasibility of clinical implementation and accuracy of the Lee-Dang method against 5 other methods while controlling sources of bias and confounding. Methods: A prospective investigation included 100 patients who met the inclusion criteria, given as follows: a diagnosis of SCI and administration of intravenous aminoglycosides (AG) or vancomycin with their dosing regimen determined by the Lee-Dang equation. The percentage of patients achieving therapeutic goal was determined, and the measured AG and vancomycin drug clearance (mCL_DRUG) values were compared with the results that were estimated from 6 equations. Results: The Lee-Dang equation was found to be more accurate, with a smaller magnitude of variance from mCL_DRUG and smaller residuals and bias compared with the alternatives. The Lee-Dang method resulted in >90% of patients achieving the steady state serum concentrations within the pre-defined goal for AG and vancomycin. All other predictive methods grossly overestimated CL_CR and produced markedly lower frequency (<50%) of achieving the goal for both antimicrobials (p < 0.05). Conclusion: The prospective data shows that the Lee-Dang method for predicting CL_CR is more accurate relative to the alternative methods in the study population with SCI, thus recommend using the Lee-Dang method for pharmacokinetic dosing of AG and vancomycin in SCI.