FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.

Pediatric burn injuries are a leading cause of morbidity with infections being the most common acute complication. Thermal injuries elicit a heightened cytokine response while suppressing immune function; however, the mechanisms leading to this dysfunction are still unknown. Our aim was to identify extracellular proteins and circulating phosphoprotein expression in the plasma after burn injury to predict the development of nosocomial infection (NI). Plasma was collected within 72 hours after injury from sixty-four pediatric burn subjects; of these, eighteen went on to develop a NI. Extracellular damage associated molecular proteins (DAMPs), FAS(APO), and protein kinase b (AKT) signaling phosphoproteins were analyzed. Subjects who went on to develop a NI had elevated high mobility group box 1 (HMGB1), heat shock protein 90 (HSP90), and FAS expression than those who did not develop a NI after injury (NoNI). Concurrently, phosphorylated (p-) AKT and mammalian target of rapamycin (p-mTOR) were elevated in those subjects who went on to develop a NI. Quadratic discriminant analysis revealed distinct differential profiles between NI and NoNI burn subjects using HSP90, FAS, and p-mTOR. The area under the receiver-operator characteristic curves displayed significant ability to distinguish between these two burn subject cohorts. These findings provide insight into predicting the signaling proteins involved in the development of NI in pediatric burn patients. Further these proteins show promise as a diagnostic tool for pediatric burn patients at risk of developing infection while additional investigation may lead to potential therapeutics to prevent NI.

Population-based study of Morganella-Proteus-Providencia group bloodstream infections.

Background: There is a paucity of studies investigating the population-based epidemiology of Morganella-Proteus-Providencia (MPP) group infections. Our objective was to determine the incidence, risk factors, and outcome of MPP group bloodstream infections (BSI), and explore species-specific differences. Methods: Population-based surveillance was conducted in the western interior of British Columbia, Canada, between April 1, 2010 and March 30, 2020. Results: Sixty-two incident MPP group BSI occurred for an annual incidence of 3.4 per 100,000 residents; rates for Morganella morganii, Proteus mirabilis, and Providencia species were 0.5, 2.6, and 0.3 per 100,000 population, respectively. The median year of age was 72.5 and was different (p = 0.03) among the groups. Most (92%) MPP group BSIs were of community-onset. Significant differences were observed in the distribution of clinical focus of infection, with most notably 81% of P. mirabilis BSI due to genitourinary focus as compared to 60% and 22% for Providencia species and M. morganii, respectively. Comorbid illnesses that increased the risk for development of MPP group BSI (incidence rate ratio; 95% CI) were HIV infection (37.0; 4.4-139.6), dementia (11.5; 6.1-20.7), cancer (6.4; 3.2-11.9), stroke 6.5 (2.8-13.3), and diabetes 2.7 (1.3-5.0). Thirteen, one, and none of the cases with P. mirabilis, M. morganii, and Providencia species BSI died within 30 days of index culture for respective all cause case-fatalities of 27%, 11%, and 0% (p = 0.1). Conclusions: Although collectively responsible for a substantial burden of illness, the epidemiology of MPP group BSI varies significantly by species.

Contexte: Il y a peu d'études qui ont étudié l'épidémiologie basée sur la population de Morganella-Proteus-Infections du groupe Providencia (MPP). L'objectif de cette étude était de déterminer l'incidence, les facteurs de risque et les résultats des bactériémies du groupe MPP (BSI) et explorer les différences spécifiques aux espèces. Méthodes: Surveillance basée sur la population a été menée auprès de résidents de l'intérieur ouest de la Colombie-Britannique, au Canada, entre le 1er avril 2010 et le 30 mars 2020. Résultats: Soixante-deux incidents du groupe MPP BSI ont été identifiés pour une incidence annuelle de 3,4 pour 100 000 habitants ; tarifs pour Morganelle morganii, Proteus mirabilis et Providencia étaient respectivement de 0,5, 2,6 et 0,3 pour 100 000 habitants. L'année médiane d'âge était de 72,5 ans et était significativement différent (p = 0,03) entre les trois groupes. La plupart (92 %) des BSI du groupe MPP étaient d'origine communautaire. Des différences significatives ont été observées dans la distribution du foyer clinique de l'infection, avec notamment 81% de P. mirabilis BSI due à la focalisation génito-urinaire par rapport à 60% et 22% pour les espèces Providencia et M. morganii, respectivement. Maladies comorbides qui augmentaient significativement le risque de développement de BSI du groupe MPP (rapport des taux d'incidence ; IC à 95 %) étaient l'infection par le VIH (37,0 ; 4,4 à 139,6), démence (11,5 ; 6,1 à 20,7), cancer (6,4 ; 3,2 à 11,9), accident vasculaire cérébral 6,5 (2,8 à 13,3) et diabète 2,7 (1,3 à 5,0). Treize, un et aucun des cas avec P. mirabilis, M. morganii et les espèces Providencia BSI sont décédés dans les 30 jours suivant la culture index pour toutes causes respectives létalités de 27 %, 11 % et 0 % (p = 0,1). Conclusions: Bien que collectivement responsables d'un lourd fardeau de maladie, l'épidémiologie des BSI du groupe MPP varie considérablement selon les espèces.