Causative pathogens, risk factors, and clinical outcomes of early-onset versus late-onset gram-negative neonatal sepsis

Background Gram-negative neonatal sepsis remains a major cause of mortality in resource-limited settings. Methods A retrospective cross-sectional study was conducted among inborn neonates admitted to the NICU within six hours of birth at Imam Khomeini Hospital, Ahvaz, Iran (2019–2023). Neonates in whom the blood culture grew gram negative bacteria were included. For microbial isolation, 1 mL of blood was inoculated into Trypticase Soy Broth. Sepsis was classified as early-onset (EOS ≤ 72 h) or late-onset (LOS > 72 h, hospital-acquired). The distribution of pathogens was described, and risk factors for late-onset sepsis (LOS) and 28-day in-hospital mortality were analyzed using multivariable logistic regression. Results Among the 201 infants, 93.5% were preterm, and 90.5% had low birth weight. The cesarean-to-vaginal delivery ratio was 1.7:1, and male-to-female ratio 1.5:1. EOS accounted for 51.2% of the cases, and LOS accounted for 48.8%. Mortality was 45.8%. Acinetobacter spp. was the most common pathogen (48.3%), significantly more frequent in LOS than EOS whereas Escherichia coli was more prevalent in EOS. Cesarean delivery and very low birth weight were significantly associated with LOS (OR were 2.798, and 2.099 respectively). In the multivariable analysis, mechanical ventilation > 3 days (AOR 6.60) and gestational age < 32 weeks (AOR 3.37) independently increased the mortality risk. Conclusion Acinetobacter spp. predominated, with distinct etiological profiles between EOS and LOS. Gram-negative sepsis has high mortality rate, especially among extremely preterm and ventilated infants. Risk factors for LOS include cesarean delivery and very low birth weight, whereas mortality is linked to extreme prematurity and prolonged ventilation. Preventive strategies targeting prematurity, prolonged ventilation, and hospital exposure may reduce LOS and mortality rates.