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

BACKGROUND: Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). METHODS: All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. RESULTS: Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. CONCLUSIONS: Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

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.

Nanotechnology and Nanocarrier-Based Drug Delivery as the Potential Therapeutic Strategy for Glioblastoma Multiforme: An Update.

Glioblastoma multiforme (GBM) is the most common and malignant brain tumor with poor prognosis. The heterogeneous and aggressive nature of GBMs increases the difficulty of current standard treatment. The presence of GBM stem cells and the blood brain barrier (BBB) further contribute to the most important compromise of chemotherapy and radiation therapy. Current suggestions to optimize GBM patients' outcomes favor controlled targeted delivery of chemotherapeutic agents to GBM cells through the BBB using nanoparticles and monoclonal antibodies. Nanotechnology and nanocarrier-based drug delivery have recently gained attention due to the characteristics of biosafety, sustained drug release, increased solubility, and enhanced drug bioactivity and BBB penetrability. In this review, we focused on recently developed nanoparticles and emerging strategies using nanocarriers for the treatment of GBMs. Current studies using nanoparticles or nanocarrier-based drug delivery system for treatment of GBMs in clinical trials, as well as the advantages and limitations, were also reviewed.

Safety and clinical application of nonbronchoscopic bronchoalveolar lavage in preterm neonates with clinical ventilator-associated pneumonia.

BACKGROUND: The safety and clinical application of nonbronchoscopic bronchoalveolar lavage (NB-BAL) in preterm neonates with ventilator-associated pneumonia (VAP) have not been fully investigated, and limited data on the feasibility of this method are available. METHODS: Premature infants with clinically suspected VAP between October 2017 and June 2019 were enrolled, and NB-BAL was performed. The tolerance and safety of NB-BAL were prospectively recorded during the procedure, and the clinical applications of NB-BAL were observed. RESULTS: A total of 46 NB-BAL procedures were performed in 31 neonates with clinically suspected VAP. The median (interquartile range) gestational age and birth body weight were 28.7 (26.7-31.3) weeks and 1055.0 (817.0-1475.0) grams, respectively. Overall, all episodes of the procedure were well tolerated, with only 9 (19.5%) episodes showing transient desaturation and one patient (2.2%) showing bradycardia during the NB-BAL procedure. There were no impairments in arterial blood gas, cardiopulmonary parameters or respiratory severity scores after NB-BAL. No significant complications occurred in any of the patients who received NB-BAL. No chronic comorbidities affected the safety and clinical application of NB-BAL in these mechanically ventilated preterm neonates. NB-BAL yielded a diagnosis in 32 (69.6%) of these VAP episodes. Staphylococcus aureus was the most common isolated bacterium and accounted for 7 (15.2%) confirmed cases of VAP in our study, followed by polymicrobial microorganisms (n = 6, 13.0%). The appropriate antibiotics were prescribed and modified according to the NB-BAL results in 25 (54.3%) cases of VAP. CONCLUSIONS: NB-BAL is a safe and clinically applicable method for determining the etiology and diagnosis of VAP in the NICU, even in extremely preterm neonates with major chronic comorbidities. Further studies to investigate the diagnostic accuracy and impact of NB-BAL on VAP treatment in neonates are warranted in the future.

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

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.