Intrapartum antibiotic prophylaxis to prevent Group B streptococcal infections in newborn infants: a systematic review and meta-analysis comparing various strategies.

Background: Early-onset Group B Streptococcus (EOGBS) infection leads to substantial morbidity and mortality in newborn infants. Intrapartum antibiotic prophylaxis (IAP) prevents EOGBS infection, but IAP strategies vary. The approach to the provision of IAP can be risk-based, universal or a combination of the two strategies.

Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection.

BACKGROUNDThe mechanism(s) responsible for the efficacy of WHO-recommended malaria vaccine RTS,S/AS01 are not completely understood. We previously identified RTS,S vaccine-induced Plasmodium falciparum circumsporozoite protein-specific (PfCSP-specific) antibody measures associated with protection from controlled human malaria infection (CHMI). Here, we tested the protection-predicting capability of these measures in independent CHMI studies.

Safety and immunogenicity after a 30-month boost of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120/MF59 vaccine boost (HVTN 100): A phase 1-2 randomized double-blind placebo-controlled trial.

Induction of broad, durable immune responses is a challenge in HIV vaccine development. HVTN 100 Part A administered subtype C-containing ALVAC-HIV at months 0 and 1, and ALVAC-HIV with bivalent subtype C gp120/MF59 at months 3, 6 and 12. As IgG binding antibody and T-cell responses were similar or greater at month 12.

Implications of ad-hoc molecular typing for infection control measures in a multi-cluster, multi-phenotypic Serratia marcescens outbreak in a neonatal intensive care unit.

Background: Serratia marcescens is known to cause outbreaks in neonatal intensive care units (NICUs). Traditionally epidemiological data, antimicrobial resistance patterns and epidemiological typing have been used to guide infection prevention methods. Whole-genome sequencing (WGS) applications such as core-genome multi-locus sequence typing (cgMLST) applied during an outbreak would potentially yield more information.

Necrotizing enterocolitis in monochorionic twins: Insights from an identical twin model.

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality in preterm neonates, yet its pathophysiology remains unclear. The aim of this study is to evaluate risk factors for NEC using an identical twin model. In this case-control study, all monochorionic twin pairs born in our center in 2002-2020 were retrospectively reviewed for NEC.

Umbilical Cord Blood as an Alternative to Neonatal Blood for Complete Blood Count: A Comparison Study.

Objective: To assess concordance between umbilical cord blood (UCB) and neonatal blood (NB) laboratory test results at birth.

Study Design: This retrospective study considered very preterm neonates (<32 weeks' gestational age) admitted to a tertiary neonatal intensive care unit from 2012 to 2023. Inclusion criteria required neonates with a complete blood count measured in both UCB and NB drawn within 2 hours after birth.

Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis.

Background: An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly.

Compliance with maternal sepsis guidelines in a tertiary hospital in the Netherlands.

Objectives: Sepsis is a common cause of maternal mortality and morbidity. Early detection and rapid management are essential. In this study, we evaluate the compliance with the implemented maternity-specific Early Warning Score (EWS), Rapid Response Team (RRT) protocol and the Surviving Sepsis Campaign (SSC) Hour-1 Bundle in a tertiary hospital in the Netherlands.

Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

Background: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives.

Aim: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs).

Methods: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed.

Influence of transition from open bay units to single room units in a neonatal intensive care unit on hospital transmission of multi-drug-resistant Enterobacterales.

Background: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital.

Improved Diagnostics in Bacterial Neonatal Meningitis Using a Next-Generation Sequencing Platform.

Introduction: Bacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics.

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials.

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals.

Group B Early-Onset Disease: New Preventive and Diagnostic Tools to Decrease the Burden of Antibiotic Use.

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low threshold for starting empirical antibiotic treatment. New guideline strategies, such as the neonatal sepsis calculator, have been proven to reduce the antibiotic burden related to EONS, but lack sensitivity for detecting EONS. In this review, the potential of novel, targeted preventive and diagnostic methods for EONS is discussed from three different perspectives: maternal, umbilical cord and newborn perspectives.

Epigenetic Immune Cell Counting to Analyze Potential Biomarkers in Preterm Infants: A Proof of Principle in Necrotizing Enterocolitis.

Epigenetic immune cell counting is a DNA (de)methylation-based technique which can be used to quantify lymphocyte subsets on dried blood spots (DBS). The foregoing techniques allow for a retrospective investigation of immune cell profiles in newborns. In this study, we used this technique for determining lymphocyte subcounts as a potential biomarker for necrotizing enterocolitis (NEC).

Developing a design-based concept to improve hand hygiene in the neonatal intensive care unit.

Background: Hand hygiene (HH) is the most critical measure in the prevention of nosocomial infections in the neonatal intensive care unit (NICU). Improving and sustaining adequate HH compliance rates, however, remains a significant challenge. Using a behavioral change framework and nudge theory, we developed a design-based concept aimed at facilitating and stimulating HH behavior.

Neonatal sepsis in alloimmune hemolytic disease of the fetus and newborn: A retrospective cohort study of 260 neonates.

Background: Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period.

Study Design And Methods: All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated.

A longitudinal analysis of nosocomial bloodstream infections among preterm neonates.

Nosocomial bloodstream infections (NBSIs), commonly due to central-line associated bloodstream infections (CLABSI), contribute substantially to neonatal morbidity and mortality. We aimed to identify longitudinal changes in incidence of NBSI, microbiological-spectrum, and antibiotic exposure in a large cohort of preterm neonates admitted to the neonatal intensive care unit. We retrospectively assessed differences in annual rates of NBSI (per 1000 patient-days), CLABSI (per 1000 central-line days), and antibiotic consumption (per 1000 patient-days) among preterm neonates (< 32 weeks' gestation) hospitalized between January 2012 and December 2020.

Regulatory T Cells in Development and Prediction of Necrotizing Enterocolitis in Preterm Neonates: A Scoping Review.

Necrotizing enterocolitis (NEC) is a leading cause of mortality in premature infants. However, the pathophysiology and influence of regulatory T cells (Tregs) have not been sufficiently elucidated. We performed a scoping review to investigate current knowledge on the influence of Tregs in NEC, and to investigate the predictive value of Treg number in NEC development.

Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition.

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT) biomarker-which quantifies the neutralization potency of antibodies in an individual's serum against an HIV-1 isolate-can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses.

Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.

Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Comparison of neonatal morbidity and mortality between single-room and open-bay care: a retrospective cohort study.

Objective: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates.

Structure and Fc-Effector Function of Rhesusized Variants of Human Anti-HIV-1 IgG1s.

Passive transfer of monoclonal antibodies (mAbs) of human origin into Non-Human Primates (NHPs), especially those which function predominantly by a Fc-effector mechanism, requires an preparation step, in which the human mAb is reengineered to an equivalent NHP IgG subclass. This can be achieved by changing both the Fc and Fab sequence while simultaneously maintaining the epitope specificity of the parent antibody. This Ab reengineering process, referred to as rhesusization, can be challenging because the simple grafting of the complementarity determining regions (CDRs) into an NHP IgG subclass may impact the functionality of the mAb.

Impact of transition from open bay to single room design neonatal intensive care unit on multidrug-resistant organism colonization rates.

Background: The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented.

Aim: To examine the effect of single room unit (SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU.

Methods: Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017.