Hepatotoxicidad en el lactante sano expuesto a nevirapina durante el embarazo / Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy

INTRODUCCIÓN: En nuestro medio, el uso de nevirapina en la embarazada infectada por el VIH se desaconseja por su potencial hepatotoxicidad. Existen pocos datos sobre dicha toxicidad en el neonato no infectado por el VIH y expuesto a este fármaco durante la gestación. Se pretende determinar el grado de hepatotoxicidad en el recién nacido expuesto a nevirapina y VIH durante la gestación. MÉTODOS: Estudio transversal observacional multicéntrico en una cohorte de recién nacidos hijos de madre VIH positivas no infectados en los que se revisó la primera determinación de alanina aminotransferasa antes de las 6 semanas de vida. Se establecieron 2 grupos según hubieran estado expuestos o no a nevirapina durante la gestación. La hepatotoxicidad se clasificó según el AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTADOS: Se incluyeron 160 recién nacidos de 159 gestaciones (88 expuestos a tratamientos combinados con nevirapina y 71 a inhibidores de proteasa). No se observó ningún caso de hepatotoxicidad según laGrading Table del DAIDS, pero se registraron 2 casos de ALT superior a los valores de normalidad (2,8%, IC 95%: 0,3-9,8) en los no expuestos a nevirapina y uno (1,1%, IC 95%: 0,0-6,1) en el grupo expuesto (p = 0,585). CONCLUSIONES: La ausencia de diferencias entre ambos grupos sugiere que los regímenes de tratamiento antirretroviral de gran actividad que incluyen nevirapina durante la gestación no asocian un riesgo aumentado de hepatopatía en el lactante con respecto a otros regímenes

BACKGROUND: The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. METHODS: A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6 weeks of age, was collected. Patients were allocated to 2 groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTS: This study included 160 newborns from 159 pregnancies (88 exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95% CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95% CI: 0.0-6.1%) in the group exposed to nevirapine (P = .585). CONCLUSION: The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations

[Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy]. / Hepatotoxicidad en el lactante sano expuesto a nevirapina durante el embarazo.

BACKGROUND: The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. METHODS: A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6weeks of age, was collected. Patients were allocated to 2groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTS: This study included 160newborns from 159pregnancies (88exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95%CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95%CI: 0.0-6.1%) in the group exposed to nevirapine (P=.585). CONCLUSION: The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations.

Staphylococcus aureus Bacteremia in Children: Changes During Eighteen Years.

BACKGROUND: Staphylococcus aureus is a major cause of bacteremia in children and is associated with high morbidity. Complete data are lacking on the incidence, related risk factors and mortality associated with this infection. METHODS: Descriptive study including patients younger than 16 years admitted to a tertiary reference hospital, with blood cultures exclusively positive for S. aureus. Four study periods were established: period 1, 1995-1999; period 2, 2000-2002; period 3, 2006-2008 and period 4, 2010-2012. RESULTS: In total, 269 episodes of S. aureus bacteremia (SAB) occurred in 242 patients. Over the total time studied, the incidence increased from 1.3 to 3.3 cases per 1000 patients hospitalized (relative risk: 2.71; 95% confidence interval: 1.85-3.95) and mortality decreased from 18% to 6% (P = 0.008). There were no differences in the resistance patterns of S. aureus strains. The prevalence of methicillin-resistant S. aureus (MRSA) increased from 3% to 13% between periods 1 and 2 and decreased from 14% to 3% between periods 3 and 4 (P = 0.011). The 30-day cumulative mortality was 3.3%, and the SAB-related mortality was 1.5%. Nosocomial acquisition and age 12-16 years were factors independently related with death on multivariate analysis. CONCLUSIONS: The incidence of SAB tripled during the years studied but remained stable in the last period. Antimicrobial resistances did not increase. Although a decrease in mortality was documented, approximately half the 30-day cumulative mortality was caused by SAB.

¿Podemos descartar infección congénita por citomegalovirus cuando la reacción en cadena de la polimerasa viral es negativa en la prueba del talón? / Can we rule out a congenital cytomegalovirus infection when the result of polymerase chain reaction in dried blood spots is negative?

INTRODUCCIÓN: La determinación de la presencia de ADN de citomegalovirus (CMV) mediante técnicas de reacción en cadena de la polimerasa a tiempo real (rt-PCR) en la gota de sangre seca en el papel absorbente usado para la realización de la prueba de detección precoz neonatal ha sido validada para el diagnóstico retrospectivo de infección congénita por CMV (CMVc) en estudios realizados en otros países, pero no en el nuestro. El objetivo de este estudio es analizar el valor diagnóstico de esta técnica en nuestro centro. MÉTODOS: Estudio retrospectivo transversal observacional de todos los pacientes con diagnóstico confirmado de CMVc entre enero de 2007 y septiembre de 2012. Se ha determinado la presencia de ADN viral de CMV en las muestras de sangre seca de la prueba del talón de estos pacientes mediante rt-PCR. RESULTADOS: Se incluyeron 14 pacientes; 4/14 sintomáticos y 4/14 con secuelas. La detección de CMV por rt-PCR fue positiva únicamente en 7 de ellos. Se demostró una relación estadísticamente significativa entre la negatividad de la rt-PCR y cargas virales más bajas al nacimiento. CONCLUSIÓN: A pesar del pequeño tamaño muestral, nuestros datos ponen en evidencia la presencia de un número importante de falsos negativos en la detección de CMV por rt-PCR en este tipo de muestras en el diagnóstico de CMVc, especialmente en pacientes con cargas virales bajas al nacimiento

INTRODUCTION: The detection of cytomegalovirus (CMV) DNA by real time polymerase chain reaction (rt-PCR) in dried blood spots collected routinely for metabolic screening has been assessed for the retrospective diagnosis of congenital CMV (cCMV) infection in many studies, but not in Spain. The aim of this study is to analyze the diagnostic accuracy of this technique in our hospital. METHODS: A cross-sectional retrospective observational study was conducted including all patients born between January, 2007 and September, 2012 with confirmed cCMV infection. The assessment of CMV DNA was made by using rt-PCR in dried blood spots of these patients. RESULTS: Fourteen patients were included: 4/14 were symptomatic and 4/14 had sequelae. The detection of CMV DNA by rt-PCR was positive in only 7 patients. A statistically significant relationship between low viral load at birth and negative rt-PCR in dried blood spots was demonstrated. CONCLUSIONS: Despite the low number of patients included, our data highlight an important amount of false negative results in the DNA CMV detection by rt-PCR in these samples for the retrospective diagnosis of cCMV infection, especially in cases with low viral load at birth

[Can we rule out a congenital cytomegalovirus infection when the result of polymerase chain reaction in dried blood spots is negative?]. / ¿Podemos descartar infección congénita por citomegalovirus cuando la reacción en cadena de la polimerasa viral es negativa en la prueba del talón?

INTRODUCTION: The detection of cytomegalovirus (CMV) DNA by real time polymerase chain reaction (rt-PCR) in dried blood spots collected routinely for metabolic screening has been assessed for the retrospective diagnosis of congenital CMV (cCMV) infection in many studies, but not in Spain. The aim of this study is to analyze the diagnostic accuracy of this technique in our hospital. METHODS: A cross-sectional retrospective observational study was conducted including all patients born between January, 2007 and September, 2012 with confirmed cCMV infection. The assessment of CMV DNA was made by using rt-PCR in dried blood spots of these patients. RESULTS: Fourteen patients were included: 4/14 were symptomatic and 4/14 had sequelae. The detection of CMV DNA by rt-PCR was positive in only 7 patients. A statistically significant relationship between low viral load at birth and negative rt-PCR in dried blood spots was demonstrated. CONCLUSIONS: Despite the low number of patients included, our data highlight an important amount of false negative results in the DNA CMV detection by rt-PCR in these samples for the retrospective diagnosis of cCMV infection, especially in cases with low viral load at birth.

[Common variable immunodeficiency. Prognostic factors for lung damage]. / Inmunodeficiencia común variable: factores pronósticos de lesión pulmonar.

BACKGROUND AND OBJECTIVE: Lung damage is considered to be key to Common Variable Immunodeficiency (CVID) prognosis. We describe lung damage in pediatric CVID patients and assess its relationship with memory B cells (MB) phenotype, immunoglobulin G (IgG) levels at the time of diagnosis, and diagnostic delay. We also assessed the prevalence of allergy and autoimmune phenomena. PATIENTS AND METHOD: Cross-sectional study of 17 CVID patients treated at Vall d'Hebron University Hospital. Prevalence ratio and prevalence odds ratio were used to assess the effect of MB cells phenotype, IgG levels and diagnostic delay on lung damage. RESULTS: Five of seventeen patients presented bronchiectasis. Diagnostic delay >5 years was significantly associated with more severe lung damage. MBO phenotype and low IgG levels at the time of diagnosis showed a trend to more severe lung damage without reaching statistical signification. A higher prevalence of allergic or autoimmune phenomena was not observed. CONCLUSIONS: Latter diagnosis is associated with greater lung damage in CVID patients. The study of MB cells should be included in the study of these patients.