Population Pharmacokinetics of Vancomycin and Meropenem in Pediatric Extracorporeal Membrane Oxygenation Support.

Objective: Describe primary pharmacokinetic/pharmacodynamic (PK/PD) parameters of vancomycin and meropenem in pediatric patients undergoing ECMO and analyze utilized dosing to reach PK/PD target. Design: Prospective, multicentric, population PK analysis. Setting: Two hospitals with pediatric intensive care unit. Patients: Pediatric patients (1 month - 15 years old) receiving vancomycin and meropenem for empiric or definitive infection treatment while ECMO support. Measurements and Main Results: Four serum concentration were obtained for patients receiving vancomycin (n = 9) and three for meropenem (n = 9). The PK/PD target for vancomycin was a ratio of the area under the curve to the minimal inhibitory concentration (AUC/MIC) of >400, and for meropenem was 4 times above MIC for 50% of the dosing interval (fT50% > 4xMIC). Pharmacokinetic modeling was performed using PMetrics 1.5.0. We included nine patients, with 11 PK profiles for each antimicrobial. The median age of patients was 4 years old (2 months - 13 years) and 45% were male. Creatinine clearance (CL) was 183 (30-550) ml/min/1.73 m2. The median dose was 13.6 (range 10-15) mg/kg every 6-12 h and 40 mg/kg every 8-12 h for vancomycin and meropenem, respectively. Two compartment models were fitted. Weight was included as a covariate on volume of the central compartment (Vc) for meropenem. Weight was included as a covariate on both Vc and clearance (CL) and serum creatinine was also included as a covariate on CL for vancomycin. The pharmacokinetic parameters CL and Vc were 0.139 ± 0.102 L/h/kg and 0.289 ± 0.295 L/kg for meropenem and 0.060 ± 0.055 L/h/kg and 0.419 ± 0.280 L/kg for vancomycin, respectively. Across each dosing interval 91% of patients achieved the PK/PD targets for adequate exposure for meropenem and 63.6% for vancomycin. Conclusion: Pharmacokinetic/pharmacodynamic objectives for vancomycin were achieved partially with conventional doses and higher dosing with extended infusion were needed in the case of meropenem.

Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With Extracorporeal Membrane Oxygenation Support.

OBJECTIVES: Determine pharmacokinetic (PK) parameters and optimal dosage of vancomycin for children on extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective PK study of vancomycin in pediatric patients on ECMO who received IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according to the presence of acute kidney injury (AKI) and requirement of renal replacement therapy (RRT). RESULTS: Data from 40 children, with a median age of 2.7 years of age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients. The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough levels were within therapeutic range in 53% of patients. After dose change, 93% of patients achieved therapeutic levels. The adjusted dose was 40 (34-60) mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1-1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7-0.9) L/kg; and half-life (t½) 6.2 (4.9-8.06) hours. In the AKI subgroup, 11 patients, the initial median dose was 40 (30-45) mg/kg/day every 8 (6-12) hours. Trough concentrations of vancomycin were within therapeutic range in 27% of patients. After dose modifications, 63% of patients achieved target trough concentration. The final adjusted dose was 20 mg/kg/day (15-30) every 12 (12-24) hours. Estimated PK parameters were Vd 1.16 (0.68-1.6) L/kg; CL 0.83 (0.38-1) mL/kg/min; and a t½ of 23.6 (16.2-31) hours. CONCLUSIONS: In patients without AKI or RRT, Vd of vancomycin was similar and CL was lower compared to pediatric critically ill patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours. In patients with AKI, the use of lower doses should be used.

[Viral respiratory co-infections in pediatric patients admitted for acute respiratory infection and their impact on clinical severity]. / Co-infección viral respiratoria en niños hospitalizados por infección respiratoria aguda y su impacto en la gravedad clínica.

INTRODUCTION: Respiratory viruses are the leading cause of acute respiratory tract infection (ARI) in children. It has been reported that viral respiratory co-infection could be associated with severe clinical course. OBJECTIVES: To describe the frequency of viral co-infection in children admitted for AlRI and evaluate whether this co-infection was associated with more severe clinical course. PATIENTS AND METHODS: Prospective, descriptive study in pediatric patients who were hospitalized for ARI, with molecular detection of at least 1 respiratory virus in nasopharyngeal sample studied by PCR-Microarray for 17 respiratory viruses. RESULTS: 110 out of 147 patients with detection of > 1 respiratory virus were included. Viral co-infection was detected in 41/110 (37%). 22/110 children (20%) were classified as moderate to severe clinical course and 88/110 (80%) were classified as mild clinical course. In the group of moderate to severe clinical course, viral respiratory co-infection was detected in 6/22 (27.3%), compared to 35/88 (39.8 %) in the mild clinical course group. No statistically significant difference was found regarding the presence of co-infection between groups (p = 0.33). CONCLUSIONS: We detected high rates of viral co-infection in children with ARI. It was not possible to demonstrate that viral co-infections were related with severe clinical course in hospitalized children.

Co-infección viral respiratoria en niños hospitalizados por infección respiratoria aguda y su impacto en la gravedad clínica / Viral respiratory co-infections in pediatric patients admitted for acute respiratory infection and their impact on clinical severity

Introduction: Respiratory viruses are the leading cause of acute respiratory tract infection (ARI) in children. It has been reported that viral respiratory co-infection could be associated with severe clinical course. Objectives: To describe the frequency of viral co-infection in children admitted for AlRI and evaluate whether this co-infection was associated with more severe clinical course. Patients and Methods: Prospective, descriptive study in pediatric patients who were hospitalized for ARI, with molecular detection of at least 1 respiratory virus in nasopharyngeal sample studied by PCR-Microarray for 17 respiratory viruses. Results: 110 out of 147 patients with detection of > 1 respiratory virus were included. Viral co-infection was detected in 41/110 (37%). 22/110 children (20%) were classified as moderate to severe clinical course and 88/110 (80%) were classified as mild clinical course. In the group of moderate to severe clinical course, viral respiratory co-infection was detected in 6/22 (27.3%), compared to 35/88 (39.8 %) in the mild clinical course group. No statistically significant difference was found regarding the presence of co-infection between groups (p = 0.33). Conclusions: We detected high rates of viral co-infection in children with ARI. It was not possible to demonstrate that viral co-infections were related with severe clinical course in hospitalized children.

Introducción: Los virus respiratorios son la principal causa de infección aguda del tracto respiratorio (IRA) en pediatría. Se ha descrito que la co-infección viral podría relacionarse con infecciones virales respiratorias de curso más grave. Objetivo: Describir la frecuencia de co-infección viral en niños hospitalizados por IRA y determinar si esta co-infección se relacionó con una evolución clínica más grave. Pacientes y Métodos: Estudio descriptivo, prospectivo, en pacientes pediátricos hospitalizados por IRA entre junio y agosto 2010, que tuvieron detección molecular de al menos un virus respiratorio en muestra nasofaríngea estudiada por RPC-microarreglo para 17 virus respiratorios. Resultados: Se incluyeron 110 de 147 pacientes con detección de > 1 virus respiratorio. Se detectó co-infección viral en 41/110 (37%). En cuanto a evolución clínica, 22/110 niños (20%) se clasificaron como evolución moderada a grave (MG) y 88/110 (80%) se clasificaron como evolución leve (L). En el grupo MG se detectó co-infección viral respiratoria en 6/22 (27,3%), mientras que en el grupo L se detectó co-infección en 35/88 (39,8%). No se encontró diferencia significativa en relación a la presencia de co-infección entre ambos grupos (p = 0,33). Conclusión: Se demostró la presencia de co-infección viral en un alto porcentaje de niños con IRA. No fue posible demostrar que la presencia de coinfección viral tenga relación con una evolución clínica más grave en estos niños hospitalizados.

Activated charcoal laryngitis in an intubated patient.

UNLABELLED: Activated charcoal is useful in the management of poisonings, but it is not harmless. We report the case of a patient who developed obstructive laryngitis secondary to aspiration of activated charcoal with a protected airway. CASE: A 2-year-old girl presented acute mental alteration secondary to presumed poisoning. Mechanical ventilation was initiated, and a single dose of activated charcoal was administered. She had an episode of vomiting during the respiratory weaning. Black-tinted tracheal secretions were suctioned through the tube immediately. Pulmonary auscultation and radiologic examination were normal. When she was extubed, she developed obstructive laryngitis. Fiberbronchoscopy was performed and showed edema and a significant amount of charcoal particles on the epiglottis, arytenoids, and arytenoepiglottic folds. Charcoal particles were removed by bronchoscopy successfully. Later evolution was normal, and no symptoms were present when she was discharged at home. COMMENTS: Obstructive laryngitis is a new major complication of activated charcoals use in upper airway. It is remarkable that this complication occurred in a protected airway. Charcoal is not an innocuous agent. This case shows that nasogastric administration of activated charcoals presents a significant degree of risk.

Salud reproductiva en el área occidente: características básicas de nacidos en maternidades urbanas / Reproductive health in the west area: basic characteristics of newborns in urban maternities

Se presenta y discute los hallazgos principales de una línea de investigación sobre salud reproductiva y características de los recién nacidos del Area Occidente (sector urbano) de Santiago, comparándolos con la información disponible para todo el país. La edad materna, en las primíparas, tiende a concentrarse en edades de riesgo menor, al igual que en todo el país. Los partos eutócidos oscilan entre 62% para las primíparas y 70,1% para las multíparas, siendo el dato obtenido por un estudio colaborativo nacional 66%. La cesárea resuelve el parto en el 23 y 26% del total (el valor a nivel nacional es de 27%). El uso de anticonceptivos en el momento de concebir es de 3,5% en primíparas y 22,5% en multíparas (valor nacional de 22,2% para ambos grupos en conjunto). El espaciamiento intergenésico muestra que cifras elevadas de no primogénitos (40,1% en Occidente y 37,7% en Chile) nacen después de un espaciamiento de 5 o más años. El peso promedio al nacer es satisfactorio pero se observa un aumento del peso inferior a 2.500 g a partir del año 1984; llegando ahora a 7,3% (7,5% en el país). Un 35,6% de las madres son solteras (32,8% en 1987, en Chile). Se analiza la reproducción de estos datos sobre el nivel de salud del país y sus eventuales proyecciones futuras