Late-onset Carbapenem-resistant Enterobacteriaceae Sepsis Among Very Preterm Infants: A Multicenter Study in China

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections are emerging as a crisis in developing countries. We aim to investigate the epidemiologic characteristics and antibiotic treatment strategies of CRE sepsis in very preterm infants (VPIs). METHOD: This cross-sectional study included all infants born at 24-31 weeks of gestation or birth weight <1500 g who developed late-onset sepsis caused by Enterobacteriaceae , as recorded in the 2022 Chinese Neonatal Network database. Late-onset sepsis was defined as sepsis occurring after 72 hours of birth. RESULTS: Of 11,447 VPIs admitted, 205 infants had 207 episodes of Enterobacteriaceae -related late-onset sepsis, of which 27 (13.0%) were caused by CRE. The most common CRE pathogens were Klebsiella spp. (66.7%, 18/27). Multivariate analysis identified prior carbapenem exposure as an independent risk factor for CRE sepsis (adjusted odds ratio: 2.33; 95% confidence interval: 1.02-5.49). In the CRE group, mortality due to Enterobacteriaceae sepsis (22.2% vs. 10.1%, P = 0.07) and all-cause mortality during hospitalization (29.6% vs. 13.5%, P = 0.04) were both higher than that in the non-CRE group. For empirical antibiotic therapy, of the 27 CRE cases, 21 (77.8%) were treated with meropenem alone and 6 (28.6%) of these infants died from CRE sepsis. For definitive therapy, 17/22 (77.3%) received monotherapy, of which 12 (70.6%) were treated with meropenem, while 5 (22.7%) received combination therapy. CONCLUSIONS: In Chinese neonatal intensive care units, 13.0% of late-onset Enterobacteriaceae sepsis in VPIs was caused by CRE, which was associated with a significant mortality rate. Meropenem-based regimens remain the primary treatment for CRE sepsis, though with a high treatment failure rate.