Population pharmacokinetics of amikacin in suspected cases of neonatal sepsis.

AIMS: This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. METHODS: Newborns aged ≥3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. RESULTS: Data from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. CONCLUSION: Our main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Infection profile in neonatal patients during extracorporeal membrane oxygenation.

OBJECTIVES: To describe risk factors for acquired infection during neonatal extracorporeal membrane oxygenation and to examine the predictive value of inflammatory markers in the diagnosis of infection. METHODS: A retrospective study was conducted with data for patients under 30 days supported with extracorporeal membrane oxygenation from 2003 to April 2016, in a neonatal intensive care unit. RESULTS: Our study included 160 neonatal patients, the average age of connection was 8.5 days and the duration of extracorporeal membrane oxygenation support was 9.7 days. The incidence of confirmed infection was 23%. Patients with confirmed infection present more frequently: vaginal delivery, lower birth weight, female sex, diagnosis of congenital diaphragmatic hernia, and longer duration of extracorporeal membrane oxygenation. When comparing the group of patients with confirmed infection and suspicion of infection, there were no significant differences in the inflammatory markers. When calculating the slope for each one, the difference in white blood cell count slope 72 h before the infection is significant; in patients with confirmed infection, the count of white blood cell increases (slope: 0.25), versus the group of patients with suspected infection in whom the count decreases (slope: -0.39). No differences were found in other variables. CONCLUSION: Our study describes that the factors that increase the risk of infection are lower birth weight, vaginal birth, duration of extracorporeal membrane oxygenation, and a positive trend of white blood cell 72 h prior to infection/suspicion. Further studies are necessary to include or definitively rule out the use of these factors and the biomarkers as predictors of infection in neonatal patients supported with extracorporeal membrane oxygenation.

[Strategies to reduce infections and antibiotic use and its effects in a neonatal care unit]. / Estrategias para reducir infecciones, uso de antimicrobianos y sus efectos en una unidad de neonatología.

INTRODUCTION: Late onset sepsis (LOS) remains an important cause of morbidity and mortality in neonatal intensive care units (NICU). The empirical use of vancomycin and other broad spectrum antibiotics is very frequent and is associated with the emergence of resistant agents, infection by gram-negative bacilli (GNB), fungal infections and increased morbidity and mortality. OBJECTIVE: To evaluate the impact of 5 intervention protocols designed to reduce infections and promote the rational use of antibiotics (AB) in a single NICU. PATIENTS AND METHOD: Retrospective analysis included all hospitalized patients before (year 2012) and after interventions (August 2013 through July 2014). All episodes of positive cultures (blood, urine, tracheal and spinal fluid) were considered as late onset infections. RESULTS: After intervention, a significant decrease of late onset infections was observed from 14.3 to 8.5 per 1,000 live births (p < 0.01); with a decrease in LOS from 5.7 to 2.9 per 1,000 live births, although no significant. There was a decrease in vancomycin and 3rd generation cephalosporin use without Candida spp infections in the intervention period. Mortality rates and length of hospital stay were similar in both study periods. CONCLUSION: After interventions, there was an important reduction in overall late onset infections and AB related costs.

Estrategias para reducir infecciones, uso de antimicrobianos y sus efectos en una unidad de neonatología / Strategies to reduce infections and antibiotic use and its effects in a neonatal care unit

Introduction: Late onset sepsis (LOS) remains an important cause of morbidity and mortality in neonatal intensive care units (NICU). The empirical use of vancomycin and other broad spectrum antibiotics is very frequent and is associated with the emergence of resistant agents, infection by gram-negative bacilli (GNB), fungal infections and increased morbidity and mortality. Objective: To evaluate the impact of 5 intervention protocols designed to reduce infections and promote the rational use of antibiotics (AB) in a single NICU. Patients and Method: Retrospective analysis included all hospitalized patients before (year 2012) and after interventions (August 2013 through July 2014). All episodes of positive cultures (blood, urine, tracheal and spinal fluid) were considered as late onset infections. Results: After intervention, a significant decrease of late onset infections was observed from 14.3 to 8.5 per 1,000 live births (p < 0.01); with a decrease in LOS from 5.7 to 2.9 per 1,000 live births, although no significant. There was a decrease in vancomycin and 3rd generation cephalosporin use without Candida spp infections in the intervention period. Mortality rates and length of hospital stay were similar in both study periods. Conclusion: After interventions, there was an important reduction in overall late onset infections and AB related costs.

Introducción: La sepsis tardía sigue siendo una causa importante de morbilidad y mortalidad en las unidades de cuidados intensivos neonatales. El uso de vancomicina y otros antimicrobianos de amplio espectro es frecuente y se asocia a la aparición de agentes resistentes, infecciones por bacilos gramnegativos, infecciones por hongos y una mayor morbimortalidad. Objetivo: Evaluar el impacto de cinco protocolos de intervención para reducir la incidencia de infecciones y promover el uso racional de antimicrobianos. Pacientes y Método: Análisis retrospectivo pre (control) y post intervenciones. Se revisaron todos los episodios de infecciones con cultivos positivos (sangre, orina, tráquea y líquido cefalorraquídeo) en pacientes hospitalizados entre enero de 2012 y junio de 2014. Resultados: Después de la intervención, hubo una disminución significativa en las infecciones tardías de 14,3 a 8,5 por 1.000 RNV (p < 0,01); con disminución de la sepsis tardía de 5,7 a 2,8 por 1.000 RNV, sin alcanzar significancia estadística. Hubo una disminución significativa del uso de vancomicina y de cefalosporinas de tercera generación, así como la desaparición de infecciones por Candida spp. La mortalidad y la estadía hospitalaria fueron similares en ambos períodos. Conclusión: Al incorporar estas intervenciones, se logró una disminución significativa de las infecciones tardías y de los costos asociados al uso de antimicrobianos.

Survival of newborn infants with severe respiratory failure before and after establishing an extracorporeal membrane oxygenation program.

BACKGROUND: Severe hypoxic respiratory failure is a leading cause of neonatal mortality in Chile. Extracorporeal membrane oxygenation improves survival in neonates with hypoxic respiratory failure. OBJECTIVE: To determine the impact of the establishment of a Neonatal Extracorporeal Membrane Oxygenation Program on the outcome of newborns with severe hypoxic respiratory failure in a developing country. DESIGN/PATIENTS: Data of newborns (birthweight > 2,000 g and gestational age ≥ 35 wk) with hypoxic respiratory failure and oxygenation index greater than 25 were compared before and after extracorporeal membrane oxygenation was available. Extracorporeal membrane oxygenation was initiated in infants with refractory hypoxic respiratory failure who failed to respond to inhaled nitric oxide/high-frequency oscillatory ventilation. MAIN RESULTS: Data from 259 infants were analyzed; 100 born in the pre-extracorporeal membrane oxygenation period and 159 born after the extracorporeal membrane oxygenation program was established. Patients were similar in terms of risk factors for death for both periods except for a higher oxygenation index and a greater proportion of outborn infants during the extracorporeal membrane oxygenation period. Survival significantly increased from 72% before extracorporeal membrane oxygenation to 89% during the extracorporeal membrane oxygenation period (p < 0.01). During the extracorporeal membrane oxygenation period, 98 of 159 patients (62%) with hypoxic respiratory failure were rescued using inhaled nitric oxide/high-frequency oscillatory ventilation, whereas 61 (38%) did not improve; 52 of these 61 neonates were placed on extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation survival rate to discharge was 85%. After adjusting for potential confounders, the severity of the pretreatment oxygenation index, a late arrival to the referral center, the presence of a pneumothorax, and the diagnosis of a diaphragmatic hernia were significantly associated with the need for extracorporeal membrane oxygenation or death. CONCLUSIONS: The establishment of an extracorporeal membrane oxygenation program was associated with a significant increase in the survival of newborns more than or equal to 35 weeks old with severe hypoxic respiratory failure.

Randomized trial of early bubble continuous positive airway pressure for very low birth weight infants.

OBJECTIVE: To determine whether very low birth weight infants (VLBWIs), initially supported with continuous positive airway pressure (CPAP) and then selectively treated with the INSURE (intubation, surfactant, and extubation to CPAP; CPAP/INSURE) protocol, need less mechanical ventilation than those supported with supplemental oxygen, surfactant, and mechanical ventilation if required (Oxygen/mechanical ventilation [MV]). STUDY DESIGN: In a multicenter randomized controlled trial, spontaneously breathing VLBWIs weighing 800-1500 g were allocated to receive either therapy. In the CPAP/INSURE group, if respiratory distress syndrome (RDS) did not occur, CPAP was discontinued after 3-6 hours. If RDS developed and the fraction of inspired oxygen (FiO(2)) was >0.35, the INSURE protocol was indicated. Failure criteria included FiO(2) >0.60, severe apnea or respiratory acidosis, and receipt of more than 2 doses of surfactant. In the Oxygen/MV group, in the presence of RDS, supplemental oxygen without CPAP was given, and if FiO(2) was >0.35, surfactant and mechanical ventilation were provided. RESULTS: A total of 256 patients were randomized to either the CPAP/INSURE group (n = 131) or the Oxygen/MV group (n = 125). The need for mechanical ventilation was lower in the CPAP/INSURE group (29.8% vs 50.4%; P = .001), as was the use of surfactant (27.5% vs 46.4%; P = .002). There were no differences in death, pneumothorax, bronchopulmonary dysplasia, and other complications of prematurity between the 2 groups. CONCLUSION: CPAP and early selective INSURE reduced the need for mechanical ventilation and surfactant in VLBWIs without increasing morbidity and death. These results may be particularly relevant for resource-limited regions.

Improvement of survival in infants with congenital diaphragmatic hernia in recent years: effect of ECMO availability and associated factors.

BACKGROUND/PURPOSE: Survival of patients with congenital diaphragmatic hernia (CDH) depends both on non-modifiable congenital conditions and on modifiable pre and postnatal management. ECMO improves survival up to 80% in neonates with CDH in the best ECMO centers worldwide. The first Neonatal ECMO Program in Chile was started in our University in 2003. Our objective is to determine the impact of a Neonatal ECMO Program in a level III NICU on newborns with CDH. METHODS: Data of all newborns with CDH admitted to our NICU was separated into two groups: pre ECMO (1996-2003) and ECMO (2003-2007). Crude and adjusted odds ratios for 24 months survival were estimated by logistic regression. RESULTS: Data of 46 newborns with CDH was analysed, 20 in the pre ECMO and 26 in the ECMO period. Patient characteristics were similar in both groups; however, 24-month survival increased significantly from 25% (5/20) in the pre ECMO period to 77% (20/26) in the ECMO period (P = 0.001). Adjusted odds ratios for 24-month survival were 26.98 for OI or= 7 and 17.5 for ECMO availability. CONCLUSIONS: The establishment of an ECMO program was associated with a significant increase in long-term survival for infants with CDH.

Parámetros de estética facial y gradiente sociogenético en niños chilenos / Facial esthetics and sociogenetic gradient parameters in chilean children

Objetivo: determinar valores antropométricos de estética facial de niños de 5 y 8 años de edad, concaracterísticas físicas y oclusales normales, pertenecientes a diferentes grupos sociogenéticos deSantiago de Chile, debido a que es un país con marcada mezcla indígena, y compararlos entre sísegún sexo y estrato para cada grupo etáreo y con los valores norteamericanos utilizados internacionalmentepublicados por Farkas. Metodos: se realizó un análisis facial basado en Arnett y Farkas,utilizando fotografía digital apoyada por examen clínico, en cuatro muestras, clasificadas según denticióny estrato. Resultados: no existen diferencias entre sexo ni estrato en Chile, ni tampoco cuando estasson comparadas con las medidas norteamericanas. Conclusiones: las mediciones antropométricasfaciales determinadas para los distintos grupos sociogenéticos en Santiago Chile no difieren entre sini con las publicadas por Farkas, por lo que estas pueden ser utilizadas en la clínica en Santiago conpoblaciones étnicamente mixtas.

Purpose: to compare anthropometric measurements of facial esthetics in 5 and 8 years old children,with normal physical and occlusal characteristics, belonging to different sociogenetic groups fromSantiago de Chile (mixed ethnic population); and with north American Caucasian parameters publishedby Farkas. Methods: a facial analysis based on Arnett and Farkas was carried out, using digitalphotography supported by a clinical examination, in four samples, according to the dentition andsociogenetic stratum. Results: the results show no differences in Chile according to sex and stratum,neither with Caucasian measurements. Conclusion: the anthropometric measurements of facialaesthetics in sociogenetic groups from Santiago are not different with Farkas Caucasian measurementsand can be used for clinical purposes in mixed ethnically Chilean populations.

Embarazo múltiple: diagnóstico y manejo ultrasonográfico / Multiple pregnancy: diagnosis and ultrasonographic management

La incidencia de embarazo gemelar es de 1 por ciento de los nacimientos, sin embargo esta condición está asociada a un alto riesgo de mortalidad y morbilidad perinatal debido a la prematuridad y a complicaciones específicas de los embarazos múltiples, como el síndrome de transfusión fetofetal, síndrome de perfusión arterial reversa gemelar y los pagos. En este artículo revisamos la importancia del ultrasonido en el diagnóstico, el manejo y el tratamiento de estas complicaciones con especial énfasis en la determinación de la corionicidad

Traumatismo dental en la infancia: del dentista al pediatra / Dental trauma in childhood: from odontologist to pediatrician

La comunicación y acuerdo en el enfrentamiento de problemas entre los diferentes profesionales de la salud es indispensable para una adecuada atención integral del niño. Los padres de niños con traumatismos dentales acuden muchas veces en primera instancia al pediatra para solicitar su opinión, por lo que es importante conocer las diferentes posibilidades de diagnóstico y tratamiento para derivar oportunamente al dentista