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OBJECTIVE. The goal was to evaluate risk factors for invasive Escherichia coli infections in the first week of life (early onset), focusing on the rule of intrapartum antibiotic use. METHODS. We conducted a retrospective case-control study. Between 1997 and 2001, case infants, defined as infants <7 days of age with E coli isolated from blond or cerebrospinal fluid, were identified in selected counties of California, Georgia, and Connecticut by the Active Bacterial Core Surveillance/Emerging Infections Program Network. Control infants (N - 1212) were identified from a labor and delivery record review of a stratified random sample of live births at the same hospitals in 1998 and 1999. RESULTS. Surveillance identified 132 E colt cases, including 68 ampicillin-resistant cases. The case fatality rate was 16% (21 of 132 cases). Two thirds of case infants were preterm, and 49% (64 of 132 infants) were born at ≤33 weeks of gestation. Fifty-three percent of case mothers (70 of 132 mothers) received intrapartum antibiotic therapy: 70% of those received ampicillin or penicillin. Low gestational age (≤33 weeks}, intrapartum fever, and membrane rupture of ≥18 hours were associated with increased odds of early-onset E coli infection. Results were similar when case subjects were limited to those infected with ampicillin-resistant strains. Exposure to any intrapartum antibiotic treatment, β-;lactam antibiotic treatment, or ≥4 hours of intrapartum antibiotic therapy was associated with increased odds of E coli infection and ampicillin-resistant infection in univariate analyses. Among preterm infants, intrapartum antibiotic exposure did not remain associated with either outcome in multivariable models. Among term infants, exposure In ≥4 hours of intrapartum antibiotic therapy was associated with decreased odds of early-onset E coli infection. CONCLUSIONS. Exposure to intrapartum antibiotic therapy did not increase the odds of invasive, early-onset E colt infection, intrapartum antibiotic therapy was effective in preventing E coli infection only among term infants. [ABSTRACT FROM AUTHOR]