Luciana Nanni

Ampicillin and penicillin concentration in serum and pleural fluid of hospitalized children with community-acquired pneumonia.

Background: Optimal therapeutic efficacy of β-lactam antibiotics for treatment of pneumococcal pneumonia is thought to be associated with the serum concentration greater than the minimum inhibitory concentration for 40–50% of the interdose interval at site of infection. Objective: Establish whether intravenous administration of ampicillin 400 mg/kg/day or penicillin 200,000 IU/kg/day in 6 divided doses reaches serum and or pleural concentrations above 4 μg/ml for at least 40% of the interdose interval. Materials and Methods: Hospitalized healthy children 1 month–14 years old with community-acquired bacterial pneumonia and empyema were eligible. Blood samples were obtained 30 min (C1) and 3 h (C2) after an antibiotic dose. Pleural fluid samples were obtained 1 and 4 h after the same dose in which blood samples were obtained. The concentrations were measured by high performance liquid chromatography. Results: The study included 17 patients treated with ampicillin and 13 treated with penicillin. For ampicillin, mean serum concentrations were C1 37.3 ± 19 μg/ml and C2 11 ± 10.2 μg/ml and mean pleural fluid concentrations were C1 25.8 ± 9.9 μg/ml and C2 16.2 ± 7.9 μg/ml. For penicillin, mean serum concentrations were C1 21.8 ± 16.4 μg/ml and C2 23.9 ± 3.4 μg/ml. Mean pleural fluid concentrations were C1 10.9 ± 2.2 μg/ml and C2 7.7 ± 3.4 μg/ml. In 8 of 30 patients, serum C2 was <4 μg/ml; in all of them serum concentrations were >4 μg/ml for >40% of the interdose interval. Conclusions: This study of the pharmacokinetics of β-lactam antibiotics in children with bacterial pneumonia may help in the development of therapeutic guidelines for the treatment of pneumococcal pneumonia.

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.

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.