Improving vancomycin prescription in critical illness through a drug use evaluation process: a weight-based dosing intervention study

Janice Li, Andrew A. Udy, Carl M.J. Kirkpatrick, Jeffrey Lipman, Jason A. Roberts

Vancomycin is currently recommended as first-line therapy for many meticillin-resistant Staphylococcus aureus (MRSA) infections. Recent guidelines have advocated loading doses (25-30 mg/kg) in critically ill patients in order to achieve therapeutic concentrations rapidly. However, weight-based loading doses are still not widely practised. A drug use evaluation was performed to improve the appropriateness of vancomycin initial doses in a population of critically ill adults. An educational intervention incorporating a vancomycin dosing protocol was carried out. Data were collected pre and post intervention. Vancomycin exposure [area under the concentration-time curve (AUC)] in the first 24h was determined using serum concentrations and the Bayesian software TCIWorks. Initial vancomycin doses and exposures were compared between the pre- and post-intervention groups using χ(2) and Mann-Whitney tests. A total of 111 vancomycin courses were analysed in the pre-intervention (n=80) and post-intervention (n=31) groups. Patients in the post-intervention group had significantly higher median weight-based initial doses (20.0mg/kg vs. 12.5mg/kg; P<0.001) compared with the pre-intervention group. This corresponded to significantly higher median vancomycin exposures (366.0 mg h/L vs. 262.5 mg h/L; P<0.01) in the post-intervention group. Despite higher weight-based initial doses, only 32.3% of patients in the post-intervention group had achieved optimal vancomycin exposures (AUC/minimum inhibitory concentration ratio ≥400) in the first 24h of therapy. A vancomycin dosing protocol improved the initial dosing of vancomycin and the proportion of patients who rapidly achieved optimal vancomycin exposures. However, subtherapeutic exposures were still prevalent and may warrant more vigilant promotion of the dosing protocol to ensure that recommended vancomycin doses are used in this population.