Optimization of an empiric vancomycin dosing algorithm for improved target concentration attainment in patients with...

Vancomycin empirical dosing studies in thermally injured patients have netted low successful target attainment and most excluded renal dysfunction, limiting applicability. In a previous study, the authors performed a retrospective analysis of 124 patients' measured pharmacokinetic parameters to calculate optimal dose and interval for intermittent infusion regimens and find predictors of clearance and total daily dose. The objective of this study was to improve the accuracy of attaining goal therapeutic targets with initial vancomycin regimens in patients with thermal injury through retrospective modeling.

In this phase 2 study, variables collected and calculated regimens in phase 1 were utilized to try and create an improved empiric vancomycin dosing algorithm in patients with thermal injury. Logistic regression was utilized to determine best predictors of dosing vancomycin every 6 and 8h. The strongest models were built as individual algorithms and tested for accuracy of target attainment. Each algorithm produced a regimen for each patient that was then tested utilizing each patient's actual measured pharmacokinetic parameters.

Univariable logistic regression of 41 variables identified 27 and 23 to be predictive of dosing every 8 or 6h, respectively. The most predictive multivariable model for dosing every 8h consisted of creatinine clearance (CrCl)≥80ml/min, Acute Kidney Injury Network classification <1, and total body surface area burned≥10 percent. For dosing every 6h, CrCl≥80ml/min, age≤40years old, days since injury≤6, and serum creatinine (SCr)≤0.8 were most predictive. Based on the top 5 multivariable models for each dosing interval, 7 algorithms were built to produce recommended regimens. The highest performing algorithm resulted in trough concentrations of <10mg/L (23%), 10-20mg/L (65%), 15-20mg/L (26%), and >20mg/L (11%); area under the concentration curve (AUC)>400mghr/L (83%); and AUC >400mghr/L without having a trough >20mg/L (72%).

The algorithm that resulted in the highest target attainment without overdosing recommended 15mg/kg dosed every 24h for CrCl≥30, every 12h for CrCl 31-79, every 8h for patients with CrCl≥80ml/min, and every 6h only if the patient with a CrCl≥80ml/min is also≤40 years old and has a SCr≤0.8. Caution is warranted for groups underrepresented in this study, such as those with very low CrCl, a low BMI, or receiving renal replacement therapy. This algorithm should be validated in other centers for patients with thermal injuries.