Antibiotic Susceptibility, Virulome, and Clinical Outcomes in European Infants with Bloodstream Infections Caused by Enterobacterales.
Laura FolgoriDomenico Di CarloFrancesco ComandatoreAurora PiazzaAdam A WitneyIlia BresestiYingfen HsiaKenneth LaingIrene MonahanJulia BielickiAlessandro AlvaroGian Vincenzo ZuccottiTim PlanchePaul T HeathMike SharlandPublished in: Antibiotics (Basel, Switzerland) (2021)
Mortality in neonates with Gram-negative bloodstream infections has remained unacceptably high. Very few data are available on the impact of resistance profiles, virulence factors, appropriateness of empirical treatment and clinical characteristics on patients' mortality. A survival analysis to investigate 28-day mortality probability and predictors was performed including (I) infants <90 days (II) with an available Enterobacterales blood isolate with (III) clinical, treatment and 28-day outcome data. Eighty-seven patients were included. Overall, 299 virulence genes were identified among all the pathogens. Escherichia coli had significantly more virulence genes identified compared with other species. A strong positive correlation between the number of resistance and virulence genes carried by each isolate was found. The cumulative probability of death obtained by the Kaplan-Meier survival analysis was 19.5%. In the descriptive analysis, early age at onset, gestational age at onset, culture positive for E. coli and number of classes of virulence genes carried by each isolate were significantly associated with mortality. By Cox multivariate regression, none of the investigated variables was significant. This pilot study has demonstrated the feasibility of investigating the association between neonatal sepsis mortality and the causative Enterobacterales isolates virulome. This relationship needs further exploration in larger studies, ideally including host immunopathological response, in order to develop a tailor-made therapeutic strategy.
Keyphrases
- escherichia coli
- pseudomonas aeruginosa
- antimicrobial resistance
- staphylococcus aureus
- gram negative
- cardiovascular events
- end stage renal disease
- biofilm formation
- ejection fraction
- newly diagnosed
- risk factors
- chronic kidney disease
- gestational age
- multidrug resistant
- intensive care unit
- data analysis
- prognostic factors
- patient reported outcomes
- gene expression
- cardiovascular disease
- type diabetes
- machine learning
- birth weight
- candida albicans
- low birth weight
- patient reported
- genetic diversity
- genome wide analysis
- deep learning
- weight loss