Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia

Abstract

It is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.

Machine Learning Approaches to Predict In-Hospital Mortality among Neonates with Clinically Suspected Sepsis in the Neonatal Intensive Care Unit

“…In the NICU, an episode of clinically suspected sepsis rarely directly causes mortality but is often associated with antibiotic exposure, infectious complications, prolonged ventilation and hospitalization and sometimes surgical intervention [ 22 , 23 , 24 ]. After neonates survive the most critically ill perinatal period, the combination of multiple factors, chronic comorbidities and subsequent nosocomial infections usually contributes to ultimate in-hospital mortality [ 25 , 26 ]. Therefore, it is often difficult to predict the final outcomes of these high-risk neonates, and this ML-based predictive model can be applicable in clinical practice.…”

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

“…Given the widespread use of broad-spectrum antibiotics in NICUs, the emergence of MDR pathogens is already a significant issue worldwide and has been the research focus in recent years [ 21 , 29 , 30 ]. MDR HAIs are often associated with more therapeutic challenges, higher rates of mortality and morbidity, and delayed appropriate antibiotic therapy [ 27 , 29 , 30 , 31 , 32 ].…”

“…We retrospectively reviewed all radiological, clinical, and microbiological data of neonatal ventilator-associated pneumonia (VAP) cases, and those fulfilling the strict diagnostic criteria of VAP in the NICU ( Appendix A Table A1 ) were enrolled. The definition of repeated or recurrent HAI isolates was based on previous studies [ 20 , 21 ]. The definition of CoNS late-onset sepsis was based on our previous publications [ 22 ].…”

Clinical characteristics and outcomes of neonates with polymicrobial ventilator-associated pneumonia in the intensive care unit

“…Onset of VAP was defined when the chest X-ray imaging was performed and endotracheal aspirates and/ or NBBAL was performed. Inappropriate empirical antibiotics were considered when one of the bacteria strains was resistant to the initial empirical treatment [25].…”