Risk factors for multidrug resistance and mortality in healthcare-associated neonatal gram-negative bloodstream infections

Purpose This study aimed to characterize pathogen distribution and antimicrobial resistance patterns of gram-negative bloodstream infections in a tertiary neonatal intensive care unit and to determine which factors were associated with multidrug resistance (MDR) and 28-day mortality. Methods In this retrospective cohort study, 197 neonates with healthcare-associated gram-negative bloodstream infections diagnosed between January 2010 and December 2025 were included. Demographic, perinatal, clinical, and microbiological data were extracted from electronic medical records. Factors associated with MDR infection and 28-day mortality were evaluated using univariable and multivariable logistic regression analyses. Results Of the 197 neonates, 114 (57.9%) had MDR gram-negative bloodstream infections. Klebsiella spp. was the most frequently isolated pathogen (51.3%), followed by Acinetobacter spp. (23.9%) and Escherichia coli (14.7%). Extended-spectrum beta-lactamase production was detected in 68.6% of isolates, MDR in 57.9%, and carbapenem resistance in 39.1%. Acinetobacter spp. showed the highest rates of carbapenem resistance (95.7%) and MDR (97.9%). In multivariable analysis, older postnatal age at infection onset, mechanical ventilation, and previous carbapenem exposure were independently associated with MDR infection, whereas appropriate empirical therapy was protective. Overall, 83 neonates (42.1%) died within 28 days. Mechanical ventilation and inotropic support were independently associated with mortality, while appropriate empirical therapy remained independently protective. MDR status and pathogen distribution were not independently associated with mortality. Conclusion Neonatal gram-negative bloodstream infections were characterized by a high burden of MDR. Mortality was more strongly related to indicators of illness severity than to microbiological resistance profiles. Appropriate empirical therapy was protective against both MDR infection and 28-day mortality.