Optimización con criterios PK/PD de la terapia con meropenem en el paciente crítico. Análisis farmacoeconómico de resultados

Abstract

Meropenem is a broad-spectrum antibiotic. It is a drug usually reserved for the treatment of infections caused by multi-drug resistant microorganisms or in the empirical treatment of patients with risk factors for multi-drug resistant microorganisms. Therefore, its use is frequent in intensive care units (ICU). Critical patients features including physiopathological and pharmacokinetic changes and infected by microorganisms with high minimum inhibitory concentration (MIC) make difficult calculating the optimal meropenem dose. The objective of our study was to analyze the use of clinical pharmacokinetics to optimize the therapy with meropenem in critically ill patients and assess a possible pharmacoeconomic benefit. This retrospective, observational, naturalistic, cohort single-centre study was conducted in critically ill patients treated with meropenem admitted in the ICU at a universitary hospital. Subjects were divided into two cohorts; cohort A if they had pharmacokinetic intervention or cohort B if not. For the pharmacokinetic analysis, two serum samples were drawn from each patient (a peak sampled at the end of the infusion and a sample in the elimination phase) for quantification of the total and (for some patients) free meropenem concentrations. Meropenem was administered in infusions of 3 hours theoretically. Individual pharmacokinetic parameters were estimated by the method of Sawchuk and Zaske. The percentage of time in which the free drug concentration exceeded 4 times the MIC of the isolated microorganism was estimated, and dose adjustment was made when necessary. All the variables required for the study were obtained from the electronic medical record and the pharmacokinetic history. The objectives of this study were to analyze and compare clinical and microbiological effectiveness and the safety of meropenem treatment in critically ill patients in both cohorts. We evaluated the type of pharmacokinetic interventions (IFs) recommended in monitored patients according to the real MICs of the isolated germs. A cost-effectiveness analysis was carried out to analyze if pharmacokinetic monitoring of meropenem, in addition to having a clinical benefit, is associated with an economic saving. In addition, a non-parametric model of meropenem was developed for critically ill patients based on values derived from our actual clinical practice. Monte Carlo simulations were used to evaluate what meropenem dosage regimens achieved the PK/PD index associated with therapeutic efficacy in this subgroup of patients. This study shows a great clinical and bacteriological benefit associated with the use of pharmacokinetic monitoring of meropenem in the infectious pathology in critically ill patients. Procalcitonin has proven to be a very useful biomarker for the use of antibiotics. In this review, it was necessary to optimize meropenem therapy in 66.23 % of the patients who were pharmacokinetic monitored (CA) and 90.19 % of these patients required a decrease in the daily dose of meropenem, which led to an important economic saving in the cohort A. There are no statistically significant differences in aspects related to safety between both cohorts. These results show that empirical dose of meropenem in critical patients usually proposed in the literature is not always adequate for real-world populations and tends to overdose this population, especially when MIC of the isolated germ is very low.