Increased risk of group B streptococcal sepsis and meningitis in HIV-exposed uninfected infants in a high-income country.

The purpose of this study is to compare group B Streptococcus (GBS) infection incidence in HIV-exposed uninfected (HEU) and HIV-unexposed (HU) infants in a Spanish cohort. We conducted a retrospective study in 5 hospitals in Madrid (Spain). Infants ≤ 90 days of life with a GBS infection were included from January 2008 to December 2017. Incidence of GBS infection in HEU and HU children was compared. HEU infants presented a sevenfold greater risk of GBS infection and a 29-fold greater risk of GBS meningitis compared to HU, with statistical significance. Early-onset infection was tenfold more frequent in HEU children, with statistical significance, and late-onset infection was almost fivefold more frequent in the HUE infants' group, without statistical significance. CONCLUSION: HEU infants presented an increased risk of GBS sepsis and meningitis. One in each 500 HEU infants of our cohort had a central nervous system infection and 1 in each 200, a GBS infection. Although etiological causes are not well understood, this should be taken into account by physicians when attending this population. WHAT IS KNOWN: • HIV-exposed uninfected infants are at higher risk of severe infections. • An increased susceptibility of these infants to group B Streptococcus infections has been described in low- and high-income countries, including a higher risk of meningitis in a South African cohort. WHAT IS NEW: • Group B Streptococcal meningitis is more frequent in HIV-exposed uninfected infants also in high-income countries. • Physicians should be aware of this increased risk when attending these infants.

Short communication: Effect of refrigerated storage on the pH and bacterial content of pasteurized human donor milk.

Once pasteurized donor milk is thawed for its administration to a preterm or sick neonate, and until it is administered, it is kept refrigerated at 4 to 6°C for 24 h. After this time, unconsumed milk is discarded. This time has not been extended, primarily because of the concern of bacterial contamination. The aim of this study was to determine the changes in pH and bacterial count when pasteurized donor milk was kept under refrigeration for a prolonged period (14 d). In this prospective study, 30 samples of pasteurized donor milk from 18 donors were analyzed. Milk was handled following the regular operating protocols established in the neonatal unit and was kept refrigerated after thawing. pH measurements and bacteriology (on blood agar and MacConkey agar plates) were performed on each sample at time 0 (immediately after thawing) and then every day for 14 d. Changes in pH of samples over time were evaluated with linear mixed-effects regression models. A slow but gradual increase in milk pH was observed starting from the first day [mean (±SD) pH of 7.30 (±0.18) at time 0 and 7.69 (±0.2) on d 14]. No bacterial growth was observed in any of the samples throughout the complete trial except in one sample, in which Bacillus flexus was isolated. In conclusion, pasteurized human donor milk maintains its microbiological quality when properly handled and refrigerated (4-6°C). The slight and continuous increase in milk pH after the first day could be due to changes in the solubility of calcium and phosphate during refrigerated storage.

Respuesta de los autores: Interleuquina-6 y diagnóstico de sepsis neonatal: algunas matizaciones / Response by the authors: Interleukin-6 and diagnosis of neonatal sepsis: some clarifications

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Utilidad de un test rápido de interleuquina-6 sérico combinado con proteína C reactiva para predecir la sepsis en recién nacidos con sospecha de infección / Usefulness of a rapid serum interleukin-6 test combined with C-reactive protein to predict sepsis in newborns with suspicion of infection

Objetivo: Evaluar el valor diagnóstico de la interleuquina-6 (IL-6) para predecir el riesgo de sepsis neonatal, a fin de diseñar un algoritmo para decidir el inicio de tratamiento antibiótico. Métodos: Se determinaron la IL-6 y la proteína C reactiva (PCR) en 42 recién nacidos (RN) con sospecha clínica de infección. Los RN se clasificaron como infección confirmada, infección probable o ausencia de infección, sobre la base de los resultados de los cultivos, las radiografías de tórax y la afectación de 4 o más áreas clínicas en una escala de 8. Las muestras para IL-6 se recogieron en la evaluación inicial y se congelaron hasta su determinación al final del estudio. El análisis de IL-6 se realizó de forma ciega mediante un test rápido. Se determinaron las curvas de características operador receptor para PCR e IL-6 frente a infección (confirmada o probable). Resultados: Once (26,2%) entre 42 casos incluidos en el estudio se clasificaron como infección confirmada o infección probable. El área bajo la curva para IL-6 fue de 0,9, con un valor de corte de 53pg/ml, sensibilidad del 90,91%, especificidad del 80%, valor predictivo positivo del 62,5% y valor predictivo negativo del 96%. El nivel de IL-6>96pg/ml o la combinación de IL-6>53+ PCR>13,3mg/l fueron los marcadores que mejor predijeron la infección (especificidad y VPP del 100%). Conclusiones: La determinación de IL-6 podría permitir demorar o suspender precozmente el tratamiento antibiótico en los recién nacidos con IL-6<54pg/ml. En los casos con IL-6>96pg/ml o IL-6>53+PCR>13,3 mg/l, el tratamiento antibiótico debería iniciarse de inmediato, dada la alta probabilidad de infección. La aplicación de un algoritmo basado en la determinación de IL-6 y PCR, en la evaluación inicial de los RN con sospecha clínica de infección, podría reducir el consumo innecesario de antibióticos (AU)

Aim: To evaluate the diagnostic value of interleukin-6 (IL-6) to predict the likelihood of neonatal sepsis in order to design an algorithm to decide antibiotic therapy.MethodsIL-6 and C-reactive protein (CRP) were determined in 42 newborns with clinical suspicion of infection. Newborns were classified as a confirmed, probable or no infection, based on the results of cultures, chest X-rays and the involvement of four or more clinical areas on a scale of eight. Samples for IL-6 were collected in the initial assessment and frozen until its determination at the end of the study. Blinded IL-6 measurements were performed using a rapid test. Receiver operator characteristics curves (ROC) for CRP and IL-6 versus infection (confirmed or probable) were determined. Results: Among the 42 cases included in the study 11 (26.2%) were classified as confirmed or probable infection. The area under curve (AUC) for IL-6 was 0.9, with a cut-off value of 53pg/ml: sensitivity 90.91%, specificity 80%, positive predictive value (PPV) 62.5% and negative (NPV) 96% The level of IL-6>96pg/ml and/or the combination of IL-6>53+CRP>13.3mg/l, were the markers that best predicted infection: specificity 100% and PPV: 100%. Conclusions: Assessment of IL-6 could allow withholding or early discontinuation of antibiotics in newborns with IL-6<54pg/ml. In cases with IL-6>96pg/ml and/or IL-6>53+ CRP>13.3, antibiotics should be started promptly, given the high likelihood of infection. Implementation of an algorithm based on the determination of IL-6 and CRP, in the initial assessment of the newborn with clinical suspicion of infection, could reduce unnecessary antibiotic therapy (AU)

[Usefulness of a rapid serum interleukin-6 test combined with C-reactive protein to predict sepsis in newborns with suspicion of infection]. / Utilidad de un test rápido de interleuquina-6 sérico combinado con proteína C reactiva para predecir la sepsis en recién nacidos con sospecha de infección.

AIM: To evaluate the diagnostic value of interleukin-6 (IL-6) to predict the likelihood of neonatal sepsis in order to design an algorithm to decide antibiotic therapy. METHODS: IL-6 and C-reactive protein (CRP) were determined in 42 newborns with clinical suspicion of infection. Newborns were classified as a confirmed, probable or no infection, based on the results of cultures, chest X-rays and the involvement of four or more clinical areas on a scale of eight. Samples for IL-6 were collected in the initial assessment and frozen until its determination at the end of the study. Blinded IL-6 measurements were performed using a rapid test. Receiver operator characteristics curves (ROC) for CRP and IL-6 versus infection (confirmed or probable) were determined. RESULTS: Among the 42 cases included in the study 11 (26.2%) were classified as confirmed or probable infection. The area under curve (AUC) for IL-6 was 0.9, with a cut-off value of 53 pg/ml: sensitivity 90.91%, specificity 80%, positive predictive value (PPV) 62.5% and negative (NPV) 96% The level of IL-6>96 pg/ml and/or the combination of IL-6>53+CRP>13.3 mg/l, were the markers that best predicted infection: specificity 100% and PPV: 100%. CONCLUSIONS: Assessment of IL-6 could allow withholding or early discontinuation of antibiotics in newborns with IL-6<54 pg/ml. In cases with IL-6>96 pg/ml and/or IL-6>53+ CRP>13.3, antibiotics should be started promptly, given the high likelihood of infection. Implementation of an algorithm based on the determination of IL-6 and CRP, in the initial assessment of the newborn with clinical suspicion of infection, could reduce unnecessary antibiotic therapy.

[Why are HIV-infected infants still being born in Spain?]. / Por qué se infectan aún niños con el virus de la inmunodeficiencia humana en España?

INTRODUCTION: Despite the success of preventive measures against mother-to-child transmission (MTCT) of human immunodeficiency virus-1 and -2 (HIV-1 and -2) in developed countries, HIV-infected infants continue to be born. The aim of this study was to evaluate failures in the prevention of MTCT and the clinical characteristics of infected infants. METHODS: The Foundation for the Investigation and Prevention of AIDS in Spain (FIPSE) Cohort in Madrid prospectively follows up children at risk of MTCT HIV born in eight public hospitals in Madrid. From May 2000 to December 2005, 632 children born to HIV-infected mothers were evaluated. Data from pregnancy follow-up, antiretroviral therapy (ART), and symptoms at diagnosis in infected infants were analyzed. RESULTS: Nine infants were infected. The rate of vertical transmission was 1.42 (95% CI 0.7-2.68). Of the nine mothers, seven had not received ART during pregnancy (and five had not received ART at delivery). Of the mothers who received ART, one had only done so for the last month of pregnancy. Two infants were given three drugs as prevention of MTCT, one received bitherapy and six received monotherapy. The median age at diagnosis was 2.4 months (range 7 days-2 years). The mean plasma viral load at diagnosis was 276,000 copies/ml (range: 11,900-1,000,000). Five of the infants were symptomatic at diagnosis (P. jirovaci pneumonia in two, sepsis in one, recurrent bacterial infections in one, hepatosplenomegaly in one). Four of the nine infants had been admitted to hospital prior to HIV diagnosis. DISCUSSION: Missed opportunities for the prevention of MTCT were identified in eight of the nine HIV-infected infants (89%). Administration of AZT during labor in HIV-infected mothers and triple therapy for the prevention of MTCT in high risk infants is not universal. Hospital admission in young infants at risk might lead to suspicion of infection in infants born to HIV-infected mothers. Improved implementation of all the preventive measures for MTCT should be encouraged.

¿Por qué se infectan aún niños con el virus de la inmunodeficiencia humana en España? / Why are HIV-infected infants still being born in Spain?

Introducción A pesar del éxito en la prevención de la transmisión vertical (TV) del virus de la inmunodeficiencia humana tipos 1 y 2 (VIH-1 y 2) en los países desarrollados, todavía siguen naciendo niños infectados. El propósito de este análisis es evaluar los fallos en la prevención de la TV y las características de los niños infectados Métodos La Cohorte FIPSE de Madrid sigue prospectivamente a los niños hijos de gestantes VIH que nacen en 8 hospitales públicos de Madrid. Desde mayo de 2000 hasta diciembre de 2005, se siguieron 632 niños. Se han analizado los datos de la gestación, seguimiento, tratamiento antirretroviral (TAR), y clínica al diagnóstico de los casos de TV. Resultados Se infectaron 9 niños. La tasa de TV fue del 1,42 % (intervalo de confianza [IC] 95 %: 0,7-2,68). 7/9 madres no recibieron TAR durante la gestación (y de ellas, cinco tampoco lo recibieron en el parto). De las madres que recibieron TAR, una sólo cumplió un mes de tratamiento. Dos niños recibieron triple terapia como prevención de la TV, un niño recibió biterapia y, el resto, monoterapia. La mediana de edad al diagnóstico fue de 2,4 meses (rango: 7 días-2 años). La carga viral media en el momento del diagnóstico fue de 276.000 copias/ml (rango: 11.900-1.000.000). Un total de 5/9 de los casos eran sintomáticos al diagnóstico (2 neumonías por Pneumocystis jiroveci, una sepsis, una infección bacteriana de repetición, una hepatoesplenomegalia). Un total de 4/9 requirieron ingreso hospitalario antes del diagnóstico de VIH. Discusión Se identificaron "oportunidades perdidas" de prevención de la TV en 8 de los 9 niños infectados (89 %). El uso de zidovudina durante el parto y la triple terapia al recién nacido de riesgo no están universalmente extendidos. El ingreso hospitalario de lactantes en riesgo de TV debería hacer sospechar una posible infección. Se debería reforzar el acceso y la implementación de todas las medidas de prevención de la TV en el sistema sanitario

Introduction Despite the success of preventive measures against mother-to-child transmission (MTCT) of human immunodeficiency virus-1 and -2 (HIV-1 and -2) in developed countries, HIV-infected infants continue to be born. The aim of this study was to evaluate failures in the prevention of MTCT and the clinical characteristics of infected infants. Methods The Foundation for the Investigation and Prevention of AIDS in Spain (FIPSE) Cohort in Madrid prospectively follows up children at risk of MTCT HIV born in eight public hospitals in Madrid. From May 2000 to December 2005, 632 children born to HIV-infected mothers were evaluated. Data from pregnancy follow-up, antiretroviral therapy (ART), and symptoms at diagnosis in infected infants were analyzed. Results Nine infants were infected. The rate of vertical transmission was 1.42 (95 % CI 0.7-2.68). Of the nine mothers, seven had not received ART during pregnancy (and five had not received ART at delivery). Of the mothers who received ART, one had only done so for the last month of pregnancy. Two infants were given three drugs as prevention of MTCT, one received bitherapy and six received monotherapy. The median age at diagnosis was 2.4 months (range 7 days-2 years). The mean plasma viral load at diagnosis was 276,000 copies/ml (range: 11,900-1,000,000). Five of the infants were symptomatic at diagnosis (P. jirovaci pneumonia in two, sepsis in one, recurrent bacterial infections in one, hepatosplenomegaly in one). Four of the nine infants had been admitted to hospital prior to HIV diagnosis. Discussion Missed opportunities for the prevention of MTCT were identified in eight of the nine HIV-infected infants (89 %). Administration of AZT during labor in HIV-infected mothers and triple therapy for the prevention of MTCT in high risk infants is not universal. Hospital admission in young infants at risk might lead to suspicion of infection in infants born to HIV-infected mothers. Improved implementation of all the preventive measures for MTCT should be encouraged

Distrofia miotónica congénita y encefalopatía hipóxico-isquémica / Congenital myotonic dystrophy and hypoxic-ischemic encephalopathy

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Poliartritis y fiebre botonosa mediterránea / Polyarthritis and Mediterranean spotted fever

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[Dopamine in hypotensive neonates. Study of 31 cases]. / Dopamina en recién nacidos hipotensos. Estudio de 31 casos.

We have studied retrospectively the effects of dopamine in 31 hypotensive newborn infants four hours to twenty days of age, which did not improve with conventional therapy. Hypotension aetiology was in 23 septic, cardiogenic and hypovolemic shock, in 6 hemodynamic instability in patients with hyalin membrane disease (HMD), and in two patients after tolazoline treatment in neonatal persistent pulmonary hypertension. Arterial blood pressure significantly increased when doses 5 to 10 mg/kg/min dopamine were used. Diuresis significantly increased comparing 8 hours before and after dopamine infusion. Dopamine was considered to be clinically effective in similar rates in septic (47.6%) and cardiogenic shock (40%), in all cases of hypovolemic shock (after volume infusion) and in hypotension produced by tolazoline; in hypotensive newborn infants with HMD was effective in 83.3%. Tachycardia was present in five infants with high dose (17.4 +/- 8.4 mcg/kg/min.), it returned to normal value when dopamine was decreased or discontinued. Dopamine efficacy and its lack of severe secondary effects justifies its use in neonatal hypotension.