Sepsis is a leading cause of mortality and morbidity in neonates. Presenting clinical symptoms are unspecific. Sensitivity and positive predictive value of biomarkers at onset of symptoms are suboptimal. Clinical suspicion therefore frequently leads to empirical antibiotic therapy in uninfected infants. The incidence of culture confirmed early-onset sepsis is rather low, around 0.4–0.8/1000 term infants in high-income countries. Six to 16 times more infants receive therapy for culture-negative sepsis in the absence of a positive blood culture. Thus, culture-negative sepsis contributes to high antibiotic consumption in neonatal units. Antibiotics may be life-saving for the few infants who are truly infected. However, overuse of broad-spectrum antibiotics increases colonization with antibiotic resistant bacteria. Antibiotic therapy also induces perturbations of the non-resilient early life microbiota with potentially long lasting negative impact on the individual‘s own health. Currently there is no uniform consensus definition for neonatal sepsis. This leads to variations in management. Two factors may reduce the number of culture-negative sepsis cases. First, obtaining adequate blood cultures (0.5–1 mL) at symptom onset is mandatory. Unless there is a strong clinical or biochemical indication to prolong antibiotics physician need to trust the culture results and to stop antibiotics for suspected sepsis within 36–48 h. Secondly, an international robust and pragmatic neonatal sepsis definition is urgently needed. Neonatal sepsis is a dynamic condition. Rigorous evaluation of clinical symptoms (“organ dysfunction”) over 36–48 h in combination with appropriately selected biomarkers (“dysregulated host response”) may be used to support or refute a sepsis diagnosis.

Objective To evaluate enteral feeding practices in neonatal units in different countries and on different continents. Design A web-based survey of 127 tertiary neonatal intensive care units in Australia, Canada, Denmark, Ireland, New Zealand, Norway, Sweden and the UK. Results 124 units (98%) responded. 59 units (48%) had a breast milk bank or access to donor human milk (Australia/New Zealand 2/27, Canada 6/29, Scandinavia 20/20 and UK/Ireland 31/48). The proportion of units initiating enteral feeding within the first 24 h of life was: 43/124 (35%) if gestational age (GA) <25 weeks, 53/124 (43%) if GA 25–27 weeks and 88/124 (71%) if GA 28–31 weeks. In general, Scandinavian units introduced enteral feeds the earliest, followed by UK/Ireland. Continuous feeding was routinely used for infants below 28 weeks' gestation in almost half of the Scandinavian units and in approximately one sixth of units in UK/Ireland, but rarely in Australia/New Zealand and Canada. Minimal enteral feeding for 4–5 days was common in Canada, but rare in Scandinavia. Target enteral feeding volume in a ‘stable’ preterm infant was 140–160 ml/kg/day in most Canadian units and 161–180 ml/kg/day or higher in units in the other regions. There were also marked regional differences in criteria for use and timing when human milk fortifier was added. Conclusions This study highlights areas of uncertainty and demonstrates marked variability in feeding practices. It provides valuable data for planning collaborative feeding trials to optimise outcome in preterm infants.

To systematically review the impact of antibiotic therapy in the neonatal period on changes in the gut microbiota and/or antibiotic resistance development. Data sources were PubMed, Embase, Medline and the Cochrane Database, supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic treatment (yes versus no, long versus short duration and/or broad- versus narrow-spectrum regimens) and subsequent changes in the gut microbiota and/or antibiotic resistance development. We evaluated risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, we used the vote-counting method to perform semi-quantitative meta-analyses. We applied the Grades of Recommendation, Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). Study protocol registration: PROSPERO CRD42015026743. We included 48 studies, comprising 3 RCTs and 45 observational studies. Prolonged antibiotic treatment was associated with reduced gut microbial diversity in all three studies investigating this outcome (very low QoE). Antibiotic treatment was associated with reduced colonization rates of protective commensal anaerobic bacteria in four of five studies (very low QoE). However, all three categories of antibiotic treatment were associated with an increased risk of antibiotic resistance development, in particular MDR in Gram-negative bacteria, and we graded the QoE for these outcomes as moderate. We are moderately confident that antibiotic treatment leads to antibiotic resistance development in neonates and it may also induce potentially disease-promoting gut microbiota alterations. Our findings emphasize the need to reduce unnecessary antibiotic treatment in neonates.

Background: Sepsis is a leading cause of neonatal morbidity and mortality. Clinical suspicion may lead to overuse of antibiotics. The objective of this study was to assess the epidemiology of early-onset sepsis (EOS) and antibiotic exposure during the first week of life in Norwegian term infants. Methods: This is a nationwide population-based study from the Norwegian Neonatal Network. During the 3-year study period (2009–2011), 20 of Norway’s 21 neonatal units prospectively collected data. Among 168,877 live-born (LB) term infants born during the study period, 10,175 (6.0%) infants were hospitalized in the first week of life and included in the study. Results: There were 91 cases of culture-confirmed EOS (0.54 per 1000 LB) and 1447 cases classified as culture-negative EOS (8.57 per 1000 LB). The majority of culture-confirmed EOS cases were caused by Gram-positives (83/91; 91%), most commonly group B streptococci (0.31 per 1000 LB). Intravenous antibiotics were administered to 3964 infants; 39% of all admissions and 2.3% of all LB term infants. Empiric therapy consisted of an aminoglycoside and either benzylpenicillin or ampicillin in 95% of the cases. The median (interquartile range) treatment duration was 8 (7–10) days for culture-confirmed EOS and 6 (5–7) days for culture-negative EOS. There was 1 EOS-attributable death (group B streptococcal EOS) during the study period. Conclusions: In this registry-based study, the incidence of culture-confirmed EOS was in line with previous international reports and the mortality was very low. A large proportion of infants without infection were treated with antibiotics. Measures should be taken to spare neonates unnecessary antibiotic treatment.