Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are widely distributed in the community. Notably, ESBL-producing E. coli have high-frequency early mother-to-child transmission. The current study determined the treatment and intervention measures among neonates with ESBL-producing E. coli meningitis. Five neonates (4 males and 1 female) with meningitis caused by ESBL-producing E. coli admitted to our center from June 2020 to July 2023 were retrospectively reviewed. The clinical characteristics and treatment effects were analyzed. There were 4 cases of early- onset sepsis and 1 case of a catheter-related bloodstream infection. Four of 5 cases were premature infants with gestational ages between 27 and 33 weeks. The clinical manifestations included fevers (n=5), lethargy (n=5), dyspnea (n=4), and microcirculation disorders (n=4). Meropenem was infused intravenously in 2 patients with a median duration of 120.5 d (range, 98-143 d) at an early dose of 40 mg/kg every 12 h and an extended infusion. Three patients were infused with 40 mg/kg every 8 h for a median duration of 28 d (range, 21-61 d). Two neonates had recurrent illnesses, three neonates developed hydrocephalus, one neonate had a cerebral hemorrhage, and one neonate had convulsions during treatment. The follow-up results showed 4 neonates had normal neuromotor development and 1 neonate had a 2-month lag in neuromotor development. Maternal perinatal infections, premature delivery, and catheter-related bloodstream infections are high-risk factors for ESBL-producing E. coli meningitis. Children with fevers and lethargy should be monitored closely. ESBL-producing E. coli infections in children with meningitis are prone to recurrences and secondary hydrocephalus. Attention should be paid to ensuring the correct high dose of the antibiotic.