PHC-004 Bayesian Approach in the Dosing of Vancomycin in the Treatment of Staphylococcal Infections

Abstract

Background Vancomycin is primarily effective against Gram-positive cocci. However, as it can only penetrate the tissue superficially, it is uncertain if it is really able to achieve concentrations of therapeutic benefit at the site of infection. Suboptimal concentrations have been associated with lack of clinical response and increased resistance. There are no clear criteria on pharmacokinetic parameters associated with a good response, although the most conservative proposals consider an AUC/MIC > 400, in pathological conditions such as pneumonia and meningitis. Some authors have described the failure to achieve these values with the usual doses when the MIC > 2. Purpose Our work evaluates the pharmacokinetic data of vancomycin in a group of 30 inpatients, and individual Bayesian estimates of the dose needed to overcome the described value of AUC/MIC > 400. Materials and MethodsWe estimated the kinetic parameters of a population of 30 patients with a staphylococcal infection through a Bayesian model with application v.1.0 Abbotbase Pharmacokinetic Systems. From each patient we obtained the MIC, and the dose required to obtain an AUC/MIC > 400. We calculated the percentage of patients who reached target values for AUC/MIC with a standard dose of 1 g/12 h and those receiving an individualised dose according to the kinetic parameters obtained by Bayesian setting. Maximum doses of 4 grammes/day were considered. ResultsMean clearance (CI 95%) obtained through Bayesian estimation was 3.91 l/h (3.2–4.6). Median MIC value was 1 mcg/ml. According to these data, 57% of patients would reach therapeutic AUC values with conventional dose. However, if the dose is set individually 90% of patients would reach the target value, with a mean calculated dose of 2300 mg (CI95%: 1550–3000). Conclusions Most patients with staphylococcal infections can be treated with vancomycin, which also contributes to cost reduction. A Bayesian approach shows better pharmacodynamic results than conventional dosing, with a 90% of patients successfully treated in a real setting. No conflict of interest.