Background and objectiveInfections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) have raised public-health concerns and are becoming a global health challenge. This study aimed to investigate changes in antimicrobial resistance of E. coli responsible for early-onset sepsis (EOS) in a perinatal center in eastern China.MethodsTwo periods, 2002 to 2008 and 2012 to 2018, were investigated. EOS was defined as the presence of a single potentially pathogenic bacterium grown from blood or cerebrospinal fluid in cultures drawn in any newborn infant within 72 hrs of birth. The changes in antimicrobial resistance of E. coli were analyzed.ResultsA total of 163 cases of EOS were identified, and E. coli continued to be the leading pathogen in our neonatal intensive care unit (NICU). Overall resistance of E. coli to third-generation cephalosporins increased from 14.3% in 2002–2008 to 46.7% in 2012–2018 (p<0.05). This resistance pattern closely parallels ESBL production. Compared to that from term infants, E. coli isolated from preterm infants had a significantly higher rate of resistance to ampicillin (93.3% vs 48.4%, p<0.01) and gentamicin (60.0% vs 9.4%, p<0.01), as well as a higher rate of ESBL production (66.7% vs 15.6%, p<0.01).ConclusionWe conclude that ESBL-producing multi-drug resistant E. coli has emerged as the major pathogen responsible for early-onset neonatal sepsis, particularly in preterm infants. Clinicians should consider this trend and attempt to select proper effective antibiotics as the empirical treatment for early-onset neonatal sepsis.