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Background and Aims

Methods

Results

Conclusions

Background and Aims

Appropriate use of antibiotics is life-saving in early-onset neonatal sepsis (EOS), but overuse of antibiotics is associated with adverse effects. We aimed to compare exposure to antibiotics and incidence of EOS in different networks and countries.

Methods

We conducted a large international study quantifying antibiotic exposure started in the first postnatal week, incidence of culture-proven EOS and mortality in infants born at a gestational age ≥ 34 weeks between 1.1.2014 and 31.12.2018.

Results

Thirteen networks in eleven countries from Europe, North America, and Australia participated in the study, reporting on 757’979 infants born ≥ 34 weeks. The proportion of neonates started on antibiotics was 2.86% (95% CI 2.83-2.90). Median duration of treatment was 9 days (IQR 7-14) for infants with EOS, and 4 days (IQR 3-6) for those without EOS. This led to an antibiotic exposure of 135 days/1000 livebirths (IQR 134-136). Incidence of EOS was 0.49/1000 livebirths (95% CI 0.45-0.55). Mortality in EOS cases was 3.2% (95% CI 1.66-5.52). Overall, 58 neonates were started on antibiotics and 273 antibiotic days were administered for one case of EOS. We observed wide variations in antibiotic exposure and EOS incidence among the thirteen networks.

Conclusions

Antibiotic exposure in the first postnatal week is considerable, and disproportionate compared to the incidence of EOS and sepsis-related mortality. Wide variations in the burden of disease and the burden of therapy highlight the importance of reporting on both dimensions, setting the base for benchmarking, quality improvement initiatives and future interventional studies.

Background and Aims

Preterm infants are prone to neonatal infections such as late-onset sepsis (LOS). The consequences are severe and potentially life-threatening. Unfortunately, often LOS presents with unspecific symptoms, and early screening laboratory tests have limited diagnostic value. Aim of our study was to build a predictive algorithm to aid doctors in earlier detection of LOS in very preterm infants.

Methods

In a retrospective cohort study, all consecutively admitted preterm infants (GA ≤ 32 weeks) from 2008 until 2019 were included. Infants were classified according to blood culture results, currently the gold standard, in LOS and control patients. Routinely and continuously measured oxygen saturation and heart rate were extracted from electronic medical records to generate features. Care was taken to not include variables indicative of existing LOS suspicion. Timing of blood culture served as proxy for LOS-onset. An equivalent timestamp was generated in GA-matched controls. Two machine learning techniques (Generalized Additive Model and Logistic Regression) were used to build a classification algorithm up to 24 hours before blood culture. Hourly predictions were generated for the total hospitalization period.

Results

389 infants with LOS were GA-matched to 1501 controls, median GA was 28.1 and 30.3 weeks, respectively. The algorithm yielded an AUC of 0.76 (p<0.05) at t=0. Sensitivity and specificity were 77% and 63%, respectively. Hourly predictions were plotted against a dashboard.

Conclusions

Our algorithm based on routinely collected data can potentially accelerate clinical decisions, even with relatively restricted inputs. Prospective validation is needed to prove benefit in clinical practice.

Background and Aims

Colistin (colistimethate sodium), a cationic polypeptide antibiotic of the polymyxin class has been reused due to its potent antimicrobial activity against multidrug-resistant Gram-negative bacteria and the lack of new antibiotics. The purpose of this study was to assess the critically ill infants treated with colistin in the neonatal intensive care unit (NICU) and the predisposing factors for the emergence of acute kidney injury (AKI) following colistin treatment.

Methods

This was a case-control study that included newborn infants with proven or suspected nosocomial infections in the NICU of Eskişehir Osmangazi University Hospital in Turkey between January 2012 and March 2022. Over the same time period, the clinical and laboratory characteristics and outcomes of patients who received colistin therapy were compared to patients who received other antimicrobial agents.

Results

Seventy seven patients were in colistin group (ColG) and 77 patients were in control group (CG). The demographic and clinical characteristics of the study groups were similar (Table1). Hyponatremia, hypokalemia, hypophospatemia, hypomagnesia, and AKI were all more common in the ColG compared to the CG (p<0.05) (Table 2). The most important finding in our study was the higher incidence of AKI and mortality in ColG, as well as the increasing nephrotoxic effect of other medicines when used in conjunction with colistin.

Conclusions

During colistin therapy, newborn infants must be closely monitored for AKI. Clinicians should be aware of an increased incidence of hyponatremia, hypokalemia, hypophosphatemia, hypomagnesia, AKI, and its consequences in infants given colistin. As awareness increases, harmful effects will decrease.

Background and Aims

Animal models imply that the perinatal exposure to antibiotics has a substantial impact on microbiome establishment of the offspring. We aimed to evaluate the effect of timing of antimicrobial prophylaxis for cesarean section before versus after cord clamping on gut microbiome composition of term born infants.

Methods

We performed an exploratory, single center randomized controlled clinical trial. We included forty pregnant women with elective cesarean section at term. The intervention group received single dose intravenous cefuroxime after cord clamping (n = 19), the control group single dose intravenous cefuroxime 30 minutes before skin incision (n = 21). The primary endpoint was microbiome signature of infants and metabolic prediction in the first days of life as determined in meconium samples by 16S rRNA gene sequencing. Secondary endpoints were microbiome composition at one month and 1 year of life.

Results

In meconium samples of the intervention group, the genus Staphylococcus pre-dominated. In the control group, the placental cross-over of cefuroxime was confirmed in cord blood. A higher amino acid and nitrogen metabolism as well as increased abundance of the genera Cutibacterium, Corynebacterium and Streptophyta were noted (indicator families: Cytophagaceae, Lactobacilaceae, Oxalobacteraceae). Predictive models of metabolic function revealed higher 2ʹfucosyllactose utilization in control group samples. In the follow-up visits, a higher abundance of the genus Clostridium was evident in the intervention group.

Conclusions

Our exploratory randomized controlled trial suggests that timing of antimicrobial prophylaxis is critical for early microbiome engraftment but not antimicrobial resistance emergence in term born infants.

Background and Aims

Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored.

Methods

In this multicenter prospective case-control study, longitudinal fecal samples from preterm infants (born before 30 weeks of gestation) developing severe NEC (Bell’s stage IIIA/IIIB) 1-3 days before diagnosis were analyzed by targeted high-performance liquid chromatography (HPLC) and compared to samples from gestational and postnatal age-matched controls.

Results

Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids – isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001).

Conclusions

Targeted HPLC pointed to several specific AAA alterations in samples collected 1-3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.

Background and Aims

Due to a lack of accurate diagnostic tools and non-specific symptoms of neonatal early-onset sepsis (EOS), infants are often unnecessarily treated with antibiotics directly after birth. We aimed to determine the diagnostic accuracy of Presepsin for EOS in both term and preterm infants.

Methods

In this prospective multicentre cohort study, all infants receiving antibiotics for suspected EOS were consecutively included. Presepsin concentrations were determined in cord blood and in blood samples collected at the time of sepsis evaluation and 3, 6, 12 and 24 hours afterwards. Diagnostic accuracy measures for clinical EOS were calculated for the different time points.

Results

In total, 333 infants were included of whom 169 were born preterm. At sepsis evaluation the area under the curve was 0.84 (95% confidence interval (CI) 0.73-0.95) in premature born infants and 0.60 (95% CI 0.50-0.70) in term born infants (Figure 1). A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and specificity of 54% in premature infants. Presepsin concentrations were stable during the first 24 hours after sepsis evaluation.

Conclusions

Presepsin seems to be an early and reliable biomarker in preterm infants and can be used to guide clinicians when to start or withhold antibiotics directly at sepsis evaluation, potentially halving antibiotic overtreatment. The diagnostic accuracy in term born infants was moderate. Future studies need to determine whether implementation of Presepsin as bedside point-of-care test is feasible and if this would lead to a safe decrease in the overtreatment with antibiotics in preterm infants.