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

Several methods have been proposed for the better estimation of creatinine clearance (CLCR) in spinal cord injury (SCI); however, there is no standard method to date. In 2011, Lee-Dang derived an equation to predict CLCR 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.

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.

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 CLCR and produced markedly lower frequency (<50%) of achieving the goal for both antimicrobials (p < 0.05).

The prospective data shows that the Lee-Dang method for predicting CLCR 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.