Noelia Speranza

Vancomycin pharmacokinetic-pharmacodynamic parameters to optimize dosage administration in critically ill children.

Objective: Critically ill children may present changes in pharmacokinetic parameters and may not reach effective concentrations of vancomycin with current dosages. The objective of this study is to calculate vancomycin pharmacokinetic parameters in critically ill children and to estimate area under the curve at 24 hrs/minimal inhibitory concentration reached for Staphylococcus aureus. Design, Setting, and Patients: Children treated with vancomycin, hospitalized in the Intensive Care Unit of the Pediatric Hospital–Centro Hospitalario Pereira Rossell, were included. Samples to determine vancomycin serum concentration were obtained on first and third days of treatment, 1 hr after the end of the third daily dose administration (maximum drug concentration) and 15 mins before the fourth (minimum drug concentration). Half-life elimination, volume of distribution, clearance, and area under the curve at 24 hrs were estimated. Vancomycin concentration values of 20–40 &mgr;g/mL (maximum drug concentration) and 5–10 &mgr;g/mL (minimum drug concentration) were considered therapeutic. Measurements and Main Results: Twenty-two children were included. On day 1, seven of 18 children for maximum drug concentration and 16 of 22 for minimum drug concentration reached concentrations in therapeutic range; on day 3, seven of 16 children for maximum drug concentration and 11 of 17 for minimum drug concentration did. Mean values of maximum drug concentration and minimum drug concentration were higher in children with negative water balance. Mean value of half-life elimination increased from day 1 to day 3. Considering a value of minimal inhibitory concentration for S. aureus of 1 &mgr;g/mL, nine of 18 children reached a relationship area under the curve at 24 hrs/minimal inhibitory concentration >400 on day 1 and seven of 15 on day 3. Considering a minimal inhibitory concentration of 2 &mgr;g/mL, one child reached it on day 1 and one on day 3. Conclusions: Critically ill children show changes in pharmacokinetic parameters. Serum concentration monitorization is necessary for dosage individualization. Most children do not reach an area under the curve at 24 hrs/minimal inhibitory concentration >400 with current dosage.

Risk factors for the acquisition of extended-spectrum beta-lactamase-producing Enterobacteriaceae in hospitalized children

1 Departamento de Bacteriología y Virología, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 2 Departamento de Pediatría, Centro Hospitalario Pereira Rossell, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 3 Departamento de Farmacología y Terapéutica. Hospital de Clínicas “Dr. Manuel Quintela”, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay 4 Laboratorio Central del Hospital Pereira Rossell, Ministerio de Salud Pública, Montevideo, Uruguay

Building capacity for active surveillance of vaccine adverse events in the Americas: A hospital-based multi-country network

New vaccines designed to prevent diseases endemic in low and middle-income countries are being introduced without prior utilization in countries with robust vaccine pharmacovigilance systems. Our aim was to build capacity for active surveillance of vaccine adverse events in the Americas. We describe the implementation of a proof-of-concept study for the feasibility of an international collaborative hospital-based active surveillance system for vaccine safety. The study was developed and implemented in 15 sentinel sites located in seven countries of the region of the Americas, under the umbrella of the World Health Organization (WHO) Global Vaccine Safety Initiative. The study evaluated the associations between measles-mumps-rubella vaccines and two well-recognized adverse events: Immune thrombocytopenic purpura (ITP) and aseptic meningitis. The regional network contributed 63 confirmed ITP and 16 confirmed aseptic meningitis eligible cases to the global study, representing, respectively, 33% and 19% of the total cases. To ensure long-term sustainability and usefulness to investigate adverse events following new vaccine introductions in low and middle-income countries, the network needs to be strengthened with additional sites and integrated into national health systems.

Parámetros farmacocinéticos de gentamicina en recién nacidos de término: ¿Es necesario monitorizar en forma sistemática sus concentraciones plasmáticas?

BACKGROUND Gentamicin is indicated as empiric treatment for neonatal sepsis. Plasmatic levels dosification of gentamicin is a common practice. The relationship between peak plasma concentration (Cmáx) with minimum inhibitory concentration (MIC) (Cmáx/MIC) is the parameter that best predicts treatment efficacy. AIM To determine pharmacokinetics of gentamicin in term newborn infants. METHODS Term newborn infants receiving gentamicin, without critical illness in which plasmatic levels of gentamicin was performed were included. Elimination clearance (Cl) elimination half-life (t½) and volume of distribution (Vd) were calculated. In each case the value of Cmax/MIC parameter was calculated, considering a MIC value of 1 μg/mL for Escherichia coli. RESULTS Thirteen newborns were included. The mean PK values were Cl: 0.26 mL/hour, Vd: 0.54 L/kg and t½: 6.8 h. Cmax/MIC was > 8 in 6 newborns. CONCLUSIONS Pharmacokinetic parameters of gentamicin are predictable in term newborn infants. With gentamicin doses normally used Cmax/MIC values reached 8 in 6 newborns. It is necessary to review the usefulness of plasma drug monitoring and gentamicin dosage in this group of newborns.Introduccion: Gentamicina es utilizada como tratamiento empirico en la sepsis neonatal. El monitoreo de su concentracion plasmatica es una practica frecuente. La relacion entre la concentracion plasmatica maxima (Cmax) y la concentracion inhibitoria minima (Cmax/ CIM) es el parametro que mejor predice la eficacia. Objetivo: Determinar los parametros farmacocineticos (FC) de gentamicina en recien nacidos (RN) de termino. Material y Metodos: Se incluyeron RN de termino, sin enfermedad critica, en tratamiento con gentamicina (4 mg/kg/24 h) en los que se realizo monitoreo de su concentracion plasmatica. Se determinaron: clearence de eliminacion (Cl), vida media de eliminacion (t½) y volumen de distribucion (Vd). Se estimo la Cmax/CIM, considerando una CIM de 1 μg/mL para Escherichia coli. Resultados: Participaron 13 RN. La media de Cmax fue 8,19 μg/mL y de Cmin 0,73 μg/mL. La media de los parametros farmacocineticos fue: Cl 0,26 mL/h, Vd 0,54 L/kg, t½ 6,8 h. La razon Cmax/CIM fue ≥ 8 en 6 de los 13 RN. Conclusiones: Los parametros FC de gentamicina en RN de termino, sin enfermedad critica, son predecibles. La posologia habitual no permitio obtener valores de Cmax/CIM > 8 en todos los casos. Es necesario revisar la necesidad de monitorizar su concentracion plasmatica en forma sistematica y la posologia de gentamicina en este grupo de pacientes.