Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs. The five most prevalent bacterial isolates in the NeoOBS study (NCT03721302) are Klebsiella pneumoniae, Acinetobacter baumannii, E. coli, Serratia marcescens and Enterobacter cloacae complex. Among these isolates, high levels of ESBL and carbapenemase encoding genes are detected along with resistance to ampicillin, gentamicin and cefotaxime, the current WHO recommended empiric regimens. The three new combinations show excellent in vitro activity against ESBL-producing K. pneumoniae and E. coli isolates. Our data should further inform and support the clinical evaluation of these three antibiotic combinations for the treatment of neonatal sepsis in areas with high rates of multidrug-resistant Gram-negative bacteria.

Antimicrobial Stewardship Programs in Neonates: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is a significant contributor to mortality and morbidity; however, the uncontrolled use of antimicrobials is associated with significant adverse effects. Our objective with this article is to review the components of neonatal antimicrobial stewardship programs (ASP) and their effects on clinical outcomes, cost-effectiveness, and antimicrobial resistance. METHODS: We selected randomized and nonrandomized trials and observational and quality improvement studies evaluating the impact of ASP with a cutoff date of May 22, 2023. The data sources for these studies included PubMed, Medline, Embase, Cochrane CENTRAL, Web of Science, and SCOPUS. Details of the ASP components and clinical outcomes were extracted into a predefined form. RESULTS: Of the 4048 studies retrieved, 70 studies (44 cohort and 26 observational studies) of >350 000 neonates met the inclusion criteria. Moderate-certainty evidence reveals a significant reduction in antimicrobial initiation in NICU (pooled risk difference [RD] 19%; 95% confidence interval [CI] 14% to 24%; 21 studies, 27 075 infants) and combined NICU and postnatal ward settings (pooled RD 8%; 95% CI 6% to 10%; 12 studies, 358 317 infants), duration of antimicrobial agents therapy (pooled RD 20%; 95% CI 10% to 30%; 9 studies, 303 604 infants), length of therapy (pooled RD 1.82 days; 95% CI 1.09 to 2.56 days; 10 studies, 157 553 infants), and use of antimicrobial agents >5 days (pooled RD 9%; 95% CI 3% to 15%; 5 studies, 9412 infants). Low-certainty evidence reveals a reduction in economic burden and drug resistance, favorable sustainability metrices, without an increase in sepsis-related mortality or the reinitiation of antimicrobial agents. Studies had heterogeneity with significant variations in ASP interventions, population settings, and outcome definitions. CONCLUSIONS: Moderate- to low-certainty evidence reveals that neonatal ASP interventions are associated with reduction in the initiation and duration of antimicrobial use, without an increase in adverse events.

Micromotor-based dual aptassay for early cost-effective diagnosis of neonatal sepsis.

Given the long-life expectancy of the newborn, research aimed at improving sepsis diagnosis and management in this population has been recognized as cost-effective, which at early stages continues to be a tremendous challenge. Despite there is not an ideal-specific biomarker, the simultaneous detection of biomarkers with different behavior during an infection such as procalcitonin (PCT) as high specificity biomarker with one of the earliest biomarkers in sepsis as interleukin-6 (IL-6) increases diagnostic performance. This is not only due to their high positive predictive value but also, since it can also help the clinician to rule out infection and thus avoid the use of antibiotics, due to their high negative predictive value. To this end, we explore a cutting-edge micromotor (MM)-based OFF-ON dual aptassay for simultaneous determination of both biomarkers in 15 min using just 2 µL of sample from low-birth-weight neonates with gestational age less than 32 weeks and birthweight below 1000 g with clinical suspicion of late-onset sepsis. The approach reached the high sensitivities demanded in the clinical scenario (LODPCT = 0.003 ng/mL, LODIL6 = 0.15 pg/mL) with excellent correlation performance (r > 0.9990, p < 0.05) of the MM-based approach with the Hospital method for both biomarkers during the analysis of diagnosed samples and reliability (Er < 6% for PCT, and Er < 4% for IL-6). The proposed approach also encompasses distinctive technical attributes in a clinical scenario since its minimal sample volume requirements and expeditious results compatible with few easy-to-obtain drops of heel stick blood samples from newborns admitted to the neonatal intensive care unit. This would enable the monitoring of both sepsis biomarkers within the initial hours after the manifestation of symptoms in high-risk neonates as a valuable tool in facilitating prompt and well-informed decisions about the initiation of antibiotic therapy.These results revealed the asset behind micromotor technology for multiplexing analysis in diagnosing neonatal sepsis, opening new avenues in low sample volume-based diagnostics.

Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Clinical and economic impacts of a modified-observational screening approach to well-appearing infants born to mothers with chorioamnionitis.

OBJECTIVE: Term infants born to mothers with chorioamnionitis are at risk for early-onset sepsis (EOS). We aimed to measure the impact of changing from a categorical to a modified-observational EOS screening approach on NICU admission, antibiotic utilization, and hospitalization costs. STUDY DESIGN: Single-center retrospective pre-post cohort study of full-term infants born to mothers with chorioamnionitis. Primary outcomes included NICU admission, antibiotic utilization, and hospitalization costs. Outcomes were adjusted for demographic variables. Budget-impact analysis was performed using bootstrapping with replication. RESULTS: 380 term infants were included (197 categorical; 183 modified-observational). There was a significant decrease in NICU admission and antibiotic utilization (p < 0.05) in the modified-observational cohort but no significant difference in per-patient total hospitalization costs. Budget-impact analysis suggested a high probability of cost savings. CONCLUSION: A modified-observational approach to evaluating term infants of mothers with chorioamnionitis can reduce NICU admission and unnecessary antibiotic therapy, and may lead to cost-savings.

Factores de riesgo asociados a sepsis neonatal en pacientes en cuidados mínimos, de la unidad de cuidados intensivos neonatales / Risk factors associated with neonatal sepsis in minimum care, in the neonatal intensive care unith

Antecedentes: La sepsis neonatal representa un desa- fío para los Servicios de Neonatología en el mundo, a pesar de los avances en estudios diagnósticos y te- rapia antimicrobiana, más del 46% de las muertes en menores de 5 años corresponden al periodo neo- natal, y dentro de ese porcentaje 15% es por sepsis. Objetivo: Caracterizar los factores de riesgo aso- ciados a sepsis neonatal en los recién nacidos ingre- sados en UCIN (Unidad de Cuidados Intensivos), en área de Cuidados Mínimos del Instituto Hondu- reño de Seguridad Social, de enero a junio del 2022. Pacientes y Metodología: Estudio cuantitativo con un alcance descriptivo, se estudiaron a 100 neonatos con el diagnóstico de sepsis neonatal ingresados en UCIN en área de cuidados mínimos, muestreo no probabilísti- co a conveniencia, con revisión de expedientes clínicos y aplicación de consentimiento informado a padre y/o tutor. Resultados: El 57% tenían entre 1 ­ 24 horas de vida al ingreso, 65.0% de género masculino, un 93.0% de raza mestiza y un 7% de raza negra. El 83.0% de las madres eran primigestas, con antecedente de infección urinaria en un 70.0% durante el tercer trimestre de ges- tación y el 15.5% con antecedente de infecciones vagi- nales. Un 7.8% con ruptura prematura de membranas, 3.9% corioamnionitis, 6.49% fiebre intraparto y 10.0% con infecciones respiratorias maternas. La fiebre fue el signo de sepsis predominante en todos los pacientes.Conclusiones: Madre entre 26-35 años, ser primípara, tener menos de tres controles prenatales durante su ges- tación se consideran factores de riesgo para sepsis neo- natal con una relación estadísticamente significativa ...(AU)

Costos directos de la infección adquirida en la comunidad en neonatos a término con bajo riesgo al nacer, Cundinamarca, Colombia / Direct costs of neonatal infection acquired in the community in full-term newborns and low risk at birth, Cundinamarca, Colombia

Resumen | Introducción. El 50 % de los episodios de sepsis neonatal se originan en la comunidad, con un gran porcentaje de mortalidad y complicaciones. Objetivo. Estimar los costos directos de la hospitalización por infección neonatal adquirida en la comunidad en neonatos a término con bajo riesgo al nacer. Materiales y métodos. Se utilizó la perspectiva del tercer pagador y la técnica de microcosteo; el horizonte de tiempo fue la duración de la hospitalización. La determinación de las situaciones generadoras de costos se obtuvo por medio de un consenso de expertos y se cuantificaron con base en la factura detallada de la atención de 337 neonatos hospitalizados. Los costos de los medicamentos se calcularon con base en el Sistema de Información de Precios de Medicamentos (SISMED) y, el de los procedimientos, según los manuales tarifarios ISS 2001 con porcentaje de ajuste y el seguro obligatorio de accidentes de tráfico (SOAT). Para incorporar la variabilidad de la información en la estimación, se obtuvo una distribución de los costos usando el método de bootstrapping. Resultados. Se incluyeron las facturas por la atención de 337 recién nacidos. El promedio de costos directos de la atención por paciente fue de COL$ 2'773.965 (desviación estándar, DE=$ 198.813,5; IC95%: $ 2'384.298 - $ 3'163.632). Las principales categorías generadoras de costos fueron la internación en la unidad de cuidados intensivos y las tecnologías en salud. Los costos siguieron una una distribución logarítmica normal (log-normal). Conclusiones. Las categorías con mayor impacto en los costos fueron la internación en la unidad neonatal y las tecnologías en salud. Los costos se ajustaron a una distribución logarítmica normal.

Abstract | Introduction: Half of the episodes of neonatal sepsis are acquired in the community with a high percentage of mortality and complications. Objective: To estimate the direct costs of hospitalizations due to systemic neonatal infection acquired in the community in low-risk newborns. Materials and methods: For the estimation of costs, we used the perspective of the health systems and the microcosting technique and we established the duration of hospitalization as the time horizon. We identified cost-generating events through expert consensus and the quantification was based on the detailed bill of 337 hospitalized newborns diagnosed with neonatal infection. The costs of the medications were calculated based on the drug price information system (SISMED) and the ISS 2001 rate manuals adjusting percentage, and the mandatory insurance rates for traffic accidents (SOAT). We used the bootstrapping method for cost distribution to incorporate data variability in the estimate. Results: We included the medical care invoices for 337 newborns. The average direct cost of care per patient was USD$ 2,773,965 (Standard Deviation, SD=USD$ 198,813.5; 95% CI: $ 2,384,298 - $ 3,163,632). The main cost-generating categories were hospitalization in intensive care units and health technologies. The costs followed a log-normal distribution. Conclusions: The categories generating the greatest impact on the care costs of newborns with infection were hospitalization in neonatal units and health technologies. The costs followed a log-normal distribution.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis

SUMMARY BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

RESUMO OBJETIVOS: Determinar a concentração do marcador de peroxidação lipídica: Malondialdeído (MDA) e dos marcadores antioxidantes: Superóxido Dismutase (SOD), Glutationa Peroxidase (GPX), Catalase (CAL) no sangue do cordão umbilical e na saliva não estimulada nas primeiras 24 e 48 horas de vida nos RNPT de mães com e sem fatores de risco para sepse neonatal precoce. METODOLOGIA: Estudo transversal com a assinatura do termo de consentimento livre esclarecido pela gestante e aplicação de um questionário padrão classificando o RNPT no Grupo 1 ou 2. RESULTADOS: Foram estudados 21 RNPT. Quanto ao gênero, peso ao nascimento, necessidade de oxigênio, uso de fototerapia, diagnóstico de sepse presumida, presença de sofrimento fetal, número de gestações, tipo de parto, uso de corticoide, rotura prematura de membranas, a presença de febre materna, a presença de corioamnionite, Apgar no 50 e 100 minuto de vida, a análise estatística foi feita com o teste de Mann-Whitney (p=0,019) na váriável GPX do sangue do cordão umbilical no grupo das mães com fatores de risco para sepse neonatal precoce. Não houve diferença estatística nas outras variáveis MDA, SOD, CAT do grupo com fatores de risco e em nenhuma variável do grupo sem fatores de risco. CONCLUSÃO: O aumento de duas vezes a concentração da GPX no sangue da veia umbilical dos RNPT do grupo das mães com fatores de risco para sepse neonatal precoce. Sem significância estatística na comparação entre a saliva e o sangue do cordão umbilical. Não houve diferença estatisticamente significante nas variáveis MDA, SOD e CAT.

Dissertação: Estudo dos fatores de risco maternos associados com a incidência de sepse neonatal precoce na maternidade Balbina Mestrinho, Manaus - AM / Study of maternal risk factores associated with Early-onset neonatal sepsis at Balbina Mestrinho Maternity Hospital, Manaus, Amazonas State

A sepse bacteriana é responsável por mais de 40% da mortalidade neonatal em todo o mundo. O recém nascido pode ser infectado a partir da mãe e do ambiente hospitalar. Nos primeiros sete dias de vida a maioria das infecções é de origem materna, portanto é importante identificar os fatores de risco mais envolvidos na sepse neonatal. A interação entre estes fatores é complexa e pode estar associada a risco elevado de infecção e a interpretação epidemiológica tradicional é muito limitada. O objetivo deste trabalho, foi identificar os fatores de risco maternos envolvidos na sepse neonatal precoce, incluindo vaginose bacteriana, microorganismos isolados na cultura de urina materna e na hemocultura do recém-nascido na sala de parto...(AU)