RESUMO
Meropenem pharmacokinetics in neonates exhibits large interindividual variability due to developmental changes occurring during the first month of life. The objective was to characterize meropenem pharmacokinetics through a population approach to determine effective dosing recommendations in neonates with severe nosocomial infections. Three blood samples from forty neonates were obtained once steady-state blood levels were achieved and plasma concentrations were determined with a validated chromatographic method. Data were used to develop and validate the one-compartment with first-order elimination population pharmacokinetic model obtained by non-linear mixed effect modeling. The final model was Clearance (L/h) = 2.23â¯×â¯Creatinine Clearance (L/h) and Volume of distribution(L) = 6.06â¯×â¯Body Surface Area(m2)â¯×â¯(1 + 0.60 if Fluticasone comedication). Doses should be adjusted based on said covariates to increase the likelihood of achieving therapeutic targets. This model explains 12.9% of the interindividual variability for meropenem clearance and 19.1% for volume of distribution. Stochastic simulations to establish initial dosing regimens to maximize the time above the MIC showed that the mean probabilities to achieve the PK/PD target (PTA) for microorganisms with a MIC of 2 and 8 µg/mL were 0.8 and 0.7 following i.v. bolus of 250 and 500 mg/m2/dose q8h, respectively. Meropenem extended 4h infusion would improve PTA in neonates with augmented creatinine clearance.
Assuntos
Infecção Hospitalar , Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Humanos , Recém-Nascido , Meropeném , Testes de Sensibilidade Microbiana , Método de Monte CarloRESUMO
OBJECTIVES: To determine the incidence of congenital cytomegalovirus (CMV) infection and the frequency of postnatal infection in a neonatal intensive care unit (NICU). METHODS: Urine samples of 135 infants who were admitted to the NICU during a 6 month period were evaluated to detect CMV using a nested PCR assay. A breast milk sample was obtained to determine viral excretion. Clinical characteristics of infected and non-infected infants were compared. RESULTS: Congenital CMV infection was confirmed in two (1.48%) infants. Post-natal infection was documented in four of 36 (11.1%) infants that were evaluated. CMV excretion was detected in 43 of 116 mothers. Gestational age of infants born to mothers who excreted CMV was shorter than that of infants of mothers with negative results (33.1 versus 34.2 weeks; p = 0.07). CONCLUSIONS: CMV excretion in breast milk is frequent and is associated to congenital and postnatal infection. Further studies are necessary to assess the impact of CMV infection during pregnancy and neonatal outcomes.