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

Abstract

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.

Influences of Initial Empiric Antibiotics with Ampicillin plus Cefotaxime on the Outcomes of Neonates with Respiratory Failure: A Propensity Score Matched Analysis

“…After the propensity score analysis, we found that ampicillin plus cefotaxime increased the risk of final adverse outcomes. The higher risk of final in-hospital mortality may be associated with the greater likelihood of MDR bacteremia, which has been documented to be associated with a higher risk of treatment failure and infectious complications [ 10 , 26 , 27 , 28 ]. The occurrence of MDR bacteremia and infectious complications will lead to a higher risk of recurrent sepsis and then a vicious circle will occur, which can explain the prolonged duration of hospitalization in neonates with initial broad-spectrum antibiotics [ 27 , 29 , 30 ].…”

Clinical and Microbiological Characteristics of Neonates with Candidemia and Impacts of Therapeutic Strategies on the Outcomes

“…We have documented that the neonates with candidemia had a significantly higher rate of septic shock at the onset than late-onset sepsis caused by Gram-positive or even some Gram-negative pathogens [ 28 ]. Additionally, most of the neonates with candidemia had underlying chronic comorbidities, which has been documented to be the independent risk factor of the final adverse outcomes [ 28 , 29 , 30 ].…”

Neonatal Paenibacilliosis:Paenibacillus thiaminolyticusas a Novel Cause of Neonatal Sepsis with High Risk of Sequelae in Uganda

“…[55][56][57] These studies assume that an appropriate antibiotic is ultimately administered within 1-3 days of symptom onset. 58 Unfortunately, P. thiaminolyticus can be difficult to recover using culture and will be consistently missed in Uganda and other parts of the world where neonatal sepsis is common. 59,60 Thus, it is likely that many infected neonates do not receive effective antimicrobial therapy at all, thus increasing the risk of mortality and serious sequelae, including PIH.…”