Multidrug-Resistant Healthcare-Associated Infections in Neonates with Severe Respiratory Failure and the Impacts of Inappropriate Initial Antibiotic Therap.

BACKGROUND: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial antibiotic therapy on the outcomes.

METHODS: We retrospectively analyzed all cases of HAIs in neonates with severe respiratory failure in a tertiary-level NICU in Taiwan between January 2014 and May 2020. All clinical features, microbiology, therapeutic interventions, and outcomes were compared between the MDR-HAI and non-MDR HAI groups. Multivariate regression analyses were used to investigate independent risk factors for sepsis-attributable mortality.

RESULTS: A total of 275 critically ill neonates with severe respiratory failure who had HAIs were enrolled. Ninety-five cases (34.5%) were caused by MDR pathogens, and 141 (51.3%) cases had positive bacterial cultures from multiple sterile sites. In this cohort, the MDR-HAI group was more likely to receive inappropriate initial antibiotic therapy (51.0% versus 4.7%, respectively; p < 0.001) and exhibit delayed control of the infectious focus (52.6% versus 37.8%, respectively; p = 0.021) compared with the non-MDR HAI group. The sepsis-attributable and final in-hospital rates were 21.8% and 37.1%, respectively, and they were comparable between the MDR-HAI and non-MDR HAI groups. Empirically broad-spectrum antibiotics were prescribed in 76.7% of cases, and inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. Independent risk factors for sepsis-attributable mortality in neonates with severe respiratory failure included the presence of septic shock (OR: 3.61; 95% CI: 1.54-8.46; p = 0.003), higher illness severity (OR: 1.33; 95% CI: 1.04-1.72; p = 0.026), and neonates with bronchopulmonary dysplasia (OR: 2.99; 95% CI: 1.47-6.09; p = 0.003).

CONCLUSIONS: MDR pathogens accounted for 34.5% of all neonatal HAIs in the NICU, but neither MDR pathogens nor inappropriate initial antibiotics were associated with final adverse outcomes. Because the overuse of broad-spectrum antibiotics has emerged as an important issue in critically ill neonates, the implementation of antimicrobial stewardship to promote the appropriate use of antimicrobials is urgently needed.