What is the incidence of Escherichia coli sepsis in the neonatal intensive care unit, overall and for early‑onset (≤ 72 hours) versus late‑onset (≥ 72 hours) neonatal sepsis, particularly among preterm (< 32 weeks gestation) or very‑low‑birth‑weight (< 1500 g) infants?

E. coli Sepsis Incidence in the NICU

E. coli is the leading cause of early-onset sepsis in preterm and very low birth weight infants in the NICU, with incidence rates of approximately 18.5 per 1,000 live births in extremely preterm neonates (22-28 weeks gestation) and rising significantly over the past two decades. 1

Overall Incidence by Gestational Age

The incidence of E. coli sepsis varies dramatically by gestational age and birth weight:

• Extremely preterm infants (22-28 weeks): 18.47 per 1,000 live births 1
• Very low birth weight infants (<1,500g): 8.68 per 1,000 live births, representing a significant increase from 5.07 per 1,000 in 2006-2009 1
• All gestational ages combined: E. coli accounts for approximately 36.6% of all early-onset sepsis cases 1

Early-Onset vs. Late-Onset Disease

E. coli demonstrates distinct patterns based on timing of infection:

• Early-onset sepsis (≤72 hours): E. coli is the predominant pathogen, particularly in preterm infants, with 68 of 131 cases (51.9%) occurring in this population 1
• Late-onset sepsis (>72 hours): E. coli accounts for approximately 83% of cases in some NICU cohorts, though this varies by institution 2
• Onset timing: 63% of E. coli early-onset sepsis presents on the first day of life 3

Geographic and Setting Variations

In low- and lower-middle-income countries, the burden is substantially higher:

• LLMICs: E. coli accounts for 15% of all Gram-negative neonatal sepsis cases 4
• NICU-specific data: 49 of 88 studies from LLMICs were conducted in NICUs, showing Gram-negative organisms (including E. coli) cause 60% of neonatal sepsis 4

Critical Risk Factors Associated with E. coli Sepsis

The following maternal and neonatal factors significantly increase E. coli sepsis risk:

• Preterm premature rupture of membranes (PPROM): 74% of E. coli cases vs. 11% of non-E. coli sepsis 3
• Prolonged rupture of membranes (>24 hours): 47% of E. coli cases 3
• Intrapartum fever: 26% of E. coli cases vs. 4% of non-E. coli sepsis 3
• Gestational age <30 weeks: 47% of E. coli cases vs. 4% of non-E. coli sepsis 3

Alarming Resistance Patterns

A critical pitfall is assuming standard ampicillin-gentamicin therapy remains effective, as resistance has increased dramatically:

• Ampicillin resistance: 79-93% of E. coli isolates in recent studies 5, 3
• Gentamicin resistance: 16-60% of isolates, with higher rates in preterm infants (60% vs. 9.4% in term infants) 6, 2
• Dual resistance (ampicillin + gentamicin): 7.8% of isolates, rendering first-line therapy completely ineffective 1
• Third-generation cephalosporin resistance: Increased from 14.3% to 46.7% over recent decades 6
• ESBL production: 66.7% in preterm infants vs. 15.6% in term infants 6

Mortality Outcomes

The mortality burden falls disproportionately on preterm infants:

• Preterm infants (<37 weeks): 29% mortality rate 1
• Very low birth weight infants: 35.3% mortality rate 5
• Term infants: No deaths reported in recent surveillance 1

Clinical Presentation

Avoid the pitfall of waiting for classic sepsis signs—93.6% of E. coli sepsis cases display illness within 72 hours of birth, requiring immediate empiric treatment after cultures are obtained. 1