Outcomes of early-phase ampicillin plus aminoglycosides versus ampicillin plus cefotaxime for preterm infants

BACKGROUND: When used as early empirical antibiotics for preterm infants, ampicillin + aminoglycosides may reduce mortality more effectively than ampicillin + cefotaxime. We compared in-hospital outcomes between early-phase ampicillin + aminoglycoside and ampicillin + cefotaxime therapy. METHODS: Preterm infants (<35 weeks' gestation) hospitalized between July 2010 and March 2022 were identified from a nationwide Japanese database. Patients received ampicillin + aminoglycoside (n = 33,204) or ampicillin + cefotaxime (n = 12,158) as early empirical therapy. We performed 2:1 propensity score-matched analysis to compare in-hospital mortality and major morbidities. Subgroup analyses were performed for infants <28 weeks' gestation. RESULTS: After 2:1 propensity score matching, mortality (2.6% vs. 2.5%; p = 0.55) and hearing impairment incidence (0.63% vs. 0.60%; p = 0.71) were similar between groups; however, among infants born at <28 weeks' gestation, hearing impairment was lower in ampicillin + aminoglycoside recipients (0.53% vs. 0.98%; p = 0.018). Ampicillin + aminoglycoside users had a lower incidence of bronchopulmonary dysplasia (21% vs. 23%, p < 0.001), retinopathy of prematurity (6.8% vs. 8.2%, p < 0.001), and hospitalization costs (USD 25,481 vs. 28,184, p < 0.001) than ampicillin + cefotaxime users. CONCLUSION: Early empirical ampicillin + aminoglycoside and ampicillin + cefotaxime therapy showed similar mortality in preterm infants. Antibiotic selection should consider resistance patterns and regimen-specific morbidities. IMPACT: Early-phase ampicillin + aminoglycoside administration in preterm infants possibly decreases mortality and morbidities (e.g., bacteremia) compared with ampicillin + cefotaxime administration. This large-scale, retrospective nationwide study enrolling 45,362 preterm infants revealed that early-phase antibiotic regimens (ampicillin + aminoglycosides/ampicillin + cefotaxime) did not affect in-hospital mortality. Ampicillin + aminoglycosides correlated with home assistive technology use, and ampicillin + cefotaxime with bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, and expensive hospitalization. The choice of early-phase antibiotics in preterm infants should be rooted in antimicrobial resistance patterns, considering the differences in morbidities between the two regimens.