Increase in Gram-Negative Bacterial Neonatal Sepsis

Source: Fleiss N, Murray TS, Feinn RS, et al. Neonatal sepsis from 2014 to 2024: the resurgence of gram-negative rods. J Pediatr. 2026;293:115031; doi: 10.1016/j.jpeds.2026.115031.Investigators from multiple institutions conducted a retrospective study to describe the incidence, pathogens, infant characteristics, and outcomes of neonatal sepsis at a single NICU during the period 2014–2024 and compare the results to a preceding period (2004–2013). For the study, they reviewed a prospectively collected surveillance database of blood stream infections (BSI) in patients at the Yale New Haven Children’s Hospital NICU. The proportion of BSI caused by different pathogens was calculated, and the medical records for infants with BSI were reviewed to obtain clinical information. BSI were classified as early onset sepsis (EOS) if the patient was ≤3 days old at the time the blood culture was obtained, and late onset sepsis (LOS) if the infant was >3 days old. The results of the analysis of the BSI data from 2014–2024 (epoch 2) and from a previous cohort of patients with BSI between 2004 and 2013 (epoch 1) were compared.During the period 2014–2024, there were 250 episodes of BSI in 233 infants. A total of 57 episodes of EOS in 57 patients were documented. EOS was caused by a gram-negative bacteria in 67.2% of cases and by a gram-positive bacteria in 32.8%. The most common pathogen was Escherichia coli (30 cases, 51.7%), followed by Group B Streptococcus (9 cases, 15.5%). Compared to epoch 1, the incidence of EOS was significantly higher in epoch 2 (0.7/1,000 live births and 1.1/1,000, respectively; P = 0.01). There was an increase in the proportion of EOS caused by E. coli in epoch 2 compared to epoch 1 (52% vs 44%), with most of the increase occurring in late preterm and term infants. Several gram-negative bacteria were isolated in epoch 2 that were not present in epoch 1. There was a decrease in EOS caused by Group B Streptococcus (34.8% in epoch 1, 15.5% in epoch 2). During epoch 2, 32 (57%) cases of EOS were associated with rupture of membranes >18 hours, compared to 9 (22%) in epoch 1 (P = 0.002). There were 193 episodes of LOS in 176 infants occurring during the period 2014—2024. The most common pathogens causing LOS were Staphylococcus aureus (30% of cases) and E coli (16%). Overall, there was a decrease in the incidence of LOS in epoch 2 compared to epoch 1 (17/1,000 live births vs 42/1,000; P <0.001). However, the sepsis-related mortality was higher in epoch 2 (25% vs 11% in epoch 1; P <0.001). Compared to epoch 1, there was an increase in LOS caused by gram-negative bacteria in epoch 2 (28.5% vs 40.0%).The authors conclude that gram-negative bacteria, particularly E. coli, became more common pathogens in EOS and LOS in 2014– 2024 compared to 2004–2013.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current authors observed a decrease in neonatal Group B Streptococcus BSIs and an increase in E. coli comparing 2014–2024 to 2004–2013. One must consider the limitations when generalizing the results from this study. It was limited to a single level IV NICU in the northeastern US that had implemented guidelines and interventions, including family-based infection prevention strategies and methicillin-resistant Staphylococcus aureus decolonization efforts,1,2 which other centers may not use. The neonates had positive blood cultures, but it is not clear that all met strict criteria for sepsis.3 The time periods for defining EOS and LOS are slightly different from those often used for Group B Streptococcus (eg, EOS often defined as occurring at fewer than 7 days of age).4 Over the course of this study, medical records transitioned from paper to electronic, and microbial identification methods changed, which may have introduced inconsistencies in variable availability.These limitations notwithstanding, a unique strength of the current study was the ability to track and compare pathogen and mortality trends longitudinally at a single institution over nearly a century. The decline in Group B Streptococcus EOS correlates with CDC guidelines for intrapartum antibiotic prophylaxis to prevent EOS, first issued in 19965 and revised in 2002.6 The US Neonatal Research Network and international centers also have reported an increase in E. coli-related BSI in neonates over these periods.7,8With the use of intrapartum antibiotic prophylaxis to prevent Group B Streptococcus EOS in neonates, gram-negative bacteria, especially E. coli, have emerged as the leading cause of EOS sepsis.We would suggest that antibiotic-associated altered maternal vaginal flora coupled with medical interventions in increasingly low birth weight and premature infants contributed to the observed increase in EOS neonatal gram-negative infections.