Abstract: Background：Overuse and misuse of empiric antibiotic use for early onset sepsis (EOS) in neonatal intensive care units (NICUs) is widespread, which is associated with adverse outcomes in preterm infants and increased risk of immunerelated diseases in children. The Antimicrobial Stewardship Program (ASP) targeting at EOS can effectively reduce the irrational use of antimicrobial drugs in premature infants. Objective：To carry out multidisciplinary collaborative ASP to shorten the course of empiric antimicrobial drug treatment for EOS, and to explore the effect of ASP in reducing the use of antimicrobial drugs in the early postnatal period in extremely premature infants. Design：Quality improvement research. Methods：Consecutive cases of premature infants who were admitted to the NICU at Children's Hospital of Fudan University within 24 hours after birth from November 1, 2020 to July 31, 2023 and had a gestational age of <32 weeks were included. Those with major congenital anomalies, death or discharge within 7 days, or definite indications for antibiotic prescription within 3 days after birth were excluded. The ASP program was implemented on October 31, 2022. Infants were divided into a control group (before the ASP) and an intervention group (after the ASP). Both two groups have the same subgroups of ruleout sepsis, clinical sepsis and confirmed sepsis. Multidisciplinary ASP team was established to evaluate whether to prescribe empirical antibiotics according to the risk factors of EOS (low, medium, high risk) and the illness severity. ASP team conducted weekly audit of antibiotics for each very premature infant, and provided recommendations and feedback under the supervision of the chief of NICU. Main outcome measures：Discontinuation rate of early antimicrobial drug (within 72 hours after birth). Results：From November 1, 2021 to October 31, 2022, 186 cases were retrospectively included in the control group with 102 ruleout sepsis cases and 80 clinical sepsis, and from November 1, 2022 to July 31, 2023, 135 cases were prospectively included in the intervention group with 58 ruleout sepsis cases and 70 clinical sepsis. There was no significant difference between the two groups and ruleout sepsis subgroups in the two groups in terms of infant and maternal characteristics and NICU treatment. Clinical sepsis neonates showed significant differences in gestational age, prenatal hormone use, prenatal intravenous antibiotic treatment, and mechanical ventilation within 7 days after birth. Among the ruleout sepsis infants, the proportion of infants who discontinued initial antibiotics within 72 hours in the preand postASP period showed a statistically significant difference (P=0.008). Ruleout sepsis neonates in the intervention subgroup had a 2.8 times higher early antibiotic discontinuation rate than those in the control subgroup (OR=2.76,95% CI: 1.285.94). The ASP program had no effect on antimicrobial drug use (length of treatment/1,000 patient days), the rate of early antimicrobial use, mortality, the incidence of late sepsis, and necrotizing enterocolitis. Conclusions：Among very preterm infants with ruleout sepsis, ASP increased the proportion of infants who discontinued empiric antibiotics within 72 hours after birth. Attention should be paid to the diagnosis of clinical sepsis and the time of empirical antibiotic discontinuation, which may increase the rate of early antibiotic discontinuation and reduce the length of treatment during hospitalization.

Key words: Antimicrobial stewardship program, Neonatal intensive care unit, Early onset sepsis, Very preterm infants