Neonatal Outcomes Following Culture-negative Late-onset Sepsis Among Preterm Infants

Background: Culture-negative late-onset sepsis (LOS) is commonly diagnosed in neonatal intensive care units, while the outcomes of neonatal culture-negative LOS are not reported for large cohorts. This study aimed to examine the incidence and neonatal outcomes for culture-negative LOS in a contemporary multicenter cohort of preterm infants. Methods: We performed a retrospective analysis of data from a cluster-randomized controlled study. Infants <34 weeks of gestation and admitted to 25 neonatal intensive care units between May 1, 2015, and April 30, 2018, were included. Culture-negative LOS was diagnosed if infants had abnormal manifestations and laboratory tests but negative blood cultures. The primary outcome was a composite of mortality or morbidities including periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) >= stage 3 or bronchopulmonary dysplasia (BPD). Results: Of 22,346 eligible infants, 1505 (6.7%) infants had culture-negative and 761 (3.4%) infants had culture-positive LOS. Compared with infants without LOS, infants with culture-negative LOS had higher rates of composite outcome (24.1% vs. 9.6%), death (3.8% vs. 1.8%), PVL (4.8% vs. 2.2%), severe ROP (3.3% vs. 1.1%) and BPD (18.1% vs. 7.0%). After adjustment, culture-negative LOS was independently associated with increased risk of composite outcome {adjusted odds ratio [aOR]: 1.8 [95% confidence interval (CI): 1.5-2.1]}, PVL [aOR: 2.0 (95% CI: 1.4-2.8)] and BPD [aOR: 1.8 (95% CI: 1.5-2.2)] relative to the absence of LOS. Conclusion: Culture-negative LOS was frequently diagnosed in preterm infants and was associated with increased risks of adverse outcomes. There is an emerging need for more precise diagnosis and treatment strategies for culture-negative LOS.