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.

Myeloid-derived suppressor cells and T cell populations in children with Multisystem Inflammatory Syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) represents a hyperinflammatory state that can result in multi-organ dysfunction and death. Myeloid-derived suppressor cells (MDSC) are an immunosuppressive cell population that expands under inflammatory conditions and suppresses T cell function. We hypothesized that MDSC would be increased in children with MIS-C and that MDSC expansion would be associated with T cell lymphopenia. METHODS: We conducted a prospective, observational study. Initial blood samples were collected within 48 h of admission. Age-matched healthy controls underwent sampling once. MDSC and T cell populations were identified by flow cytometric methods. RESULTS: We enrolled 22 children with MIS-C (12 ICU, 10 ward) and 21 healthy controls (HC). Children with MIS-C demonstrated significantly higher MDSC compared to HC, and MDSC expansion persisted for >3 weeks in the ICU group. Children with MIS-C admitted to the ICU demonstrated significantly lower absolute numbers of T cells and natural killer cells. There were no significant associations between MDSC and cardiac dysfunction, duration of hospitalization, or vasoactive inotrope score. CONCLUSIONS: Our study suggests that children critically ill with MIS-C have expansion of MDSC and associated decreased T cell and NK cell populations. Our results did not demonstrate associations between MDSC and clinical outcomes. IMPACT: Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated immune response occurring several weeks after SARS-CoV-2 infection that can result in multi-organ dysfunction and death. Children severely ill with MIS-C demonstrated increased myeloid-derived suppressor cells and decreased absolute numbers of CD4+ and CD8 + T cells and NK cells compared to healthy controls. There was no significant association between MDSC numbers and clinical outcomes; including cardiac dysfunction, length of stay, or requirement of vasoactive support, in children with MIS-C.

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.

Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock.

OBJECTIVES: Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls. DESIGN: Prospective observational study. SETTING: Fifty-four bed PICU in a quaternary-care children's hospital. PATIENTS: Eighteen children with septic shock and thirty age-matched healthy children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly ( p = 0.02). CONCLUSIONS: This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Measures of Adaptive Immune Function Predict the Risk of Nosocomial Infection in Pediatric Burn Patients.

Thermal injury results in changes in the inflammatory and innate immune response of pediatric patients. Plasma cytokines, cellular profiles, and reduction in innate immune function following burn injury have also been correlated to adverse outcomes (e.g., mortality and infectious complications). Changes in adaptive immune function following thermal injury are not as well characterized. Our goal was to better understand if adaptive immune dysfunction occurs early after pediatric thermal injury and is a risk factor for nosocomial infections (NIs). A prospective, longitudinal immune function observational study was performed at a single American Burn Association (ABA)-verified pediatric burn center. Eighty burn patients were enrolled with 20 developing NI, defined using Centers for Disease Control and Prevention (CDC) criteria. We collected whole blood samples from pediatric burn patients within the first 72 hours from injury and between days 4 and 7, where applicable to analyze adaptive immune function. We compared immune function between burn patients who went on to develop NI and those that did not. Within the first 72 hours of injury, burn patients who developed NI had significantly lower absolute CD4+ lymphocyte counts and whole blood ex vivo phytohemagglutinin (PHA)-induced interferon gamma (IFNγ) and interleukin-10 (IL-10) production capacity compared to those that did not develop infection. Further analysis using receiver operating characteristic curve revealed that PHA-induced IL-10 production capacity had the highest area under the curve. Our data demonstrate that early adaptive immune suppression occurs following pediatric thermal injury and PHA-induced IL-10 production capacity appears to be a predictor for the development of NI.

Impaired T-Lymphocyte Responses During Childhood Staphylococcus aureus Infection.

BACKGROUND: Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood. METHODS: We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children. RESULTS: S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype. CONCLUSIONS: These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.

Escherichia coli bloodstream infections in the western interior of British Columbia, Canada: a population-based cohort study.

Our population-based study objectives were to describe characteristics and outcomes of Escherichia coli bloodstream infections (BSIs), and to evaluate factors associated with outcomes. We included incident E. coli BSIs from western interior residents (British Columbia, Canada; 04/2010-03/2020). We obtained data including patient demographics, location of onset, infection focus, Charlson comorbidity index (CCI), antimicrobial resistance, 30-day all-cause mortality and length of hospital stay (LOS). Using multivariable logistic regression models fitted with generalised estimating equations, we estimated factors associated with 30-day mortality and long post-infection LOS (>75th percentile). We identified 1080 incident E. coli BSIs in 1009 patients. The crude incidence and 30-day mortality rates were 59.1 BSIs and 6.8 deaths/100 000 person-years, respectively. The 30-day case fatality risk was 11.5%. Compared to community-acquired E. coli BSIs, either healthcare-associated or nosocomial cases had higher odds of 30-day mortality. Older cases, non-urogenital BSI foci and CCI ⩾ 3 had higher odds of 30-day mortality compared to younger cases, urogenital foci and CCI < 3. In patients that survived to discharge, those with extended-spectrum ß-lactamase (ESBL)-producing E. coli BSIs, nosocomial BSIs, and CCI ⩾ 3 had higher odds of long post-infection LOS compared to those with non-ESBL-producing, community-acquired and healthcare-associated, and CCI < 3. There is a substantial disease burden from E. coli BSIs.

Determinants and outcomes of bloodstream infection in adults associated with one versus two sets of positive index blood cultures.

OBJECTIVES: To investigate whether positivity in one or both index sets of blood cultures influences clinical determinants and mortality when diagnosing bloodstream infections (BSI). METHODS: Retrospective population-based surveillance of all mono-microbial BSI was conducted among residents of the western interior of British Columbia. Clinical details were obtained by chart review and all-cause case-fatality was established at 30 days. Index cultures were defined as the first two sets of cultures initially drawn to diagnose incident BSI. RESULTS: A total of 2500 incident BSI were identified of which 945 (37.8%) and 1555 (62.2%) were based on one and two positive index cultures, respectively. There was an overall difference in the distribution of pathogens, with both Staphylococcus aureus and Streptococcus pneumoniae more likely to have two positive index cultures. Different foci of infection were associated with one versus two positive index cultures. Overall, 409 patients died within 30 days of index BSI for an all-cause case-fatality of 16.4%; with no difference between two positive (250/1555; 16.1%) and one positive (159/945; 16.8%; p 0.3) index blood culture. The number of positive index blood cultures was not associated with 30-day case-fatality after adjustment for confounding variables using logistic regression analysis. CONCLUSIONS: Although approximately one-third of BSI are diagnosed on the basis of a single positive blood culture and are associated with different clinical determinants, whether one or both index blood cultures are positive is not associated with lethal outcome.

Adaptations of transfusion systems to the COVID-19 pandemic in British Columbia, Canada: Early experiences of a large tertiary care center and survey of provincial activities.

BACKGROUND: In March 2020, a state of emergency was declared to facilitate organized responses to the coronavirus disease 2019 (COVID-19) pandemic in British Columbia, Canada. Emergency blood management committees (EBMCs) were formed regionally and provincially to coordinate transfusion service activities and responses to possible national blood shortages. STUDY DESIGN AND METHODS: We describe the responses of transfusion services to COVID-19 in regional health authorities in British Columbia through a collaborative survey, contingency planning meeting minutes, and policy documents, including early trends observed in blood product usage. RESULTS: Early strategic response policies were developed locally in collaboration with members of the provincial EBMC and focused on three key areas: utilization management strategies, stakeholder engagement (collaboration with frequent users of the transfusion service, advance notification of potential inventory shortage plans, and development of blood triage guidance documents), and laboratory staffing and infection control procedures. Reductions in transfusion volumes were observed beginning in mid-March 2020 for red blood cells and platelets relative to the prepandemic baseline (27% and 26% from the preceding year, respectively). There was a slow gradual return toward baseline beginning one month later; no product shortage issues were experienced. CONCLUSION: Provincial collaborative efforts facilitated the development of initiatives focused on minimizing potential COVID-19-related disruptions in transfusion services in British Columbia. While there have been no supply issues to date, the framework developed early in the pandemic should facilitate timely responses to possible disruptions in future waves of infection.

Burden of bloodstream infection in older persons: a population-based study.

BACKGROUND: Advancing age is a major risk factor for developing and dying from bloodstream infections (BSI). However, there is a paucity of population-based studies investigating the epidemiology of BSI in older persons. OBJECTIVE: To define the incidence, clinical determinants, and risk factors for death among those aged 65 years and older with BSI. METHODS: Population-based surveillance was conducted in the western interior of British Columbia, Canada, between April 1, 2010 and March 31, 2020. Chart reviews were conducted for clinical details and all cause case-fatality was established at 30-days follow-up. RESULTS: A total of 1854 incident BSI were identified among 1657 individuals aged 65 and older for an annual incidence of 533.9 per 100,000 population; the incidence for those aged 65-74, 75-84, and ≥85 years was 375.3, 678.9, and 1046.6 per 100,000 population, respectively. Males were at significantly increased risk as compared to females (incidence rate ratio, IRR 1.44; 95% confidence interval, CI, 1.32-1.59; p<0.0001). The crude annual incidence increased by 50% during the study. However, this was related to shift in population demographics with no increase evident following age- and sex-standardization. Older patients were more likely to have healthcare-associated infections and genitourinary sources and less likely to have bone/joint or soft tissue infections. The proportion of patients with underlying congestive heart failure, stroke, and dementia increased, whereas diabetes and liver disease decreased with older age. The overall 30-day all cause case-fatality rate was 22.0% (364/1657). After adjustment for clinical focus, onset of infection, etiology, and co-morbidity in a logistic model, those aged 75-84 years (odds ratio, OR, 1.66; 95% CI, 1.25-2.21) and ≥ 85 years (OR, 1.98; 95% CI, 1.41-2.77) were at significantly increased risk for death as compared to those aged 65-74 years. CONCLUSION: Bloodstream infection is common in older persons and is a major cause of death. Countries with aging populations worldwide should expect an increase burden associated with BSI in the coming years.

A Randomized Study Using Telepresence Robots for Behavioral Health in Interprofessional Practice and Education.

Background: The events of the coronavirus disease 2019 (COVID-19) pandemic forced the world to adopt telemedicine frameworks to comply with isolation and stay-at-home regulations. Telemedicine, in various forms, has been used by patients and medical professionals for quite some time, especially telepsychiatry. To examine the efficacy and role of telesimulation as a method to educate health sciences students via telepresence robots. The study recruited students from the above health science disciplines. All participants were trained to administer a contextual interview to a standardized patient (SP) for mental health concerns. Methods: The completion of the contextual interview observation form adult (CIOF-A), National Aeronautics and Space Administration Task Load Index, self-efficacy in patient centeredness questionnaire (SEPCQ), and communication skills attitude scale with or without a telepresence robot. All participants completed baseline metrics and were trained to conduct a contextual interview to an SP. Researchers block-randomized the participants to either the telepresence robot group (TP) or in-person (IP) group. Results: The study recruited n = 43 participants to the IP group (n = 21) or TP group (n = 22). Mean participant demographics of age were 25.3 (±1.9) years in the IP group and 24.3 (±2.1) years for the TP group. Mean and standard deviation scores with effect sizes in CIOF-A scores IP: 0.05 (±1.91) and TP: -0.45 (±1.71), Cohen's d = 0.28; SEPCQ-Patient Domain scores IP: 0.42 (±4.69) and TP: 0.50 (±7.18), Cohen's d = 0.01; change in SEPCQ-Sharing Domain scores IP: 0.53 (±5.10) and TP: 0.91 (±9.98), Cohen's d = 0.05. These effect sizes will inform future studies and appropriate sample sizes. Conclusion: These data indicate that health sciences students utilizing a telepresence robot in an SP scenario to perform a behavioral health screening felt as comfortable and competent as those health sciences students performing the same behavioral health screening in person. ClinicalTrials.gov Identifier: NCT03661372.

Staphylococcus aureus bloodstream infection: Secular changes associated with the implementation of a de novo clinical infectious diseases service in a Canadian population.

OBJECTIVE: To investigate the epidemiology of Staphylococcus aureus bloodstream infections (BSI) in a mixed rural to small city population and examine secular changes associated with the implementation of a regional clinical infectious diseases program. METHODS: Population-based surveillance for incident S. aureus BSI was conducted in the western interior of British Columbia, Canada between April 2010 and March 2020. An infectious diseases service was progressively implemented starting in 2013. RESULTS: 581 incident S. aureus BSI were identified. There was an increasing incidence during the study and the overall age- and gender-adjusted annual rate was 32.9 per 100,000 population. Implementation of the infectious diseases program was associated with an increase in rates of blood culture sampling, documentation of persistent bacteremia, use of transthoracic and transesophageal echocardiography, and a reduction in cases of relapsed BSI. Infectious diseases consultation was independently associated with a reduced risk for death (odds ratio 0.5; 95% CI 0.3-0.9). CONCLUSIONS: Although the implementation of a clinical infectious diseases service was associated with changes in management and improved outcome, S. aureus BSI still causes a major burden of illness.

Hydrocortisone treatment is associated with a longer duration of MODS in pediatric patients with severe sepsis and immunoparalysis.

BACKGROUND: Severe critical illness-induced immune suppression, termed immunoparalysis, is associated with longer duration of organ dysfunction in septic children. mRNA studies have suggested differential benefit of hydrocortisone in septic children based on their immune phenotype, but this has not been shown using a functional readout of the immune response. This study represents a secondary analysis of a prospectively conducted immunophenotyping study of pediatric severe sepsis to test the hypothesis that hydrocortisone will be differentially associated with clinical outcomes in children with or without immunoparalysis. METHODS: Children with severe sepsis/septic shock underwent blood sampling within 48 h of sepsis onset. Immune function was measured by quantifying whole blood ex vivo LPS-induced TNFα production capacity, with a TNFα response < 200 pg/ml being diagnostic of immunoparalysis. The primary outcome measure was number of days in 14 with MODS. Univariate and multivariable negative binomial regression models were used to examine associations between hydrocortisone use, immune function, and duration of MODS. RESULTS: One hundred two children were enrolled (age 75 [6-160] months, 60% male). Thirty-one subjects received hydrocortisone and were more likely to be older (106 [52-184] vs 38 [3-153] months, p = 0.04), to have baseline immunocompromise (32 vs 8%, p = 0.006), to have higher PRISM III (13 [8-18] vs 7 [5-13], p = 0.0003) and vasoactive inotrope scores (20 [10-35] vs 10 [3-15], p = 0.0002) scores, and to have more MODS days (3 [1-9] vs 1 [0-3], p = 0.002). Thirty-three subjects had immunoparalysis (TNFα response 78 [52-141] vs 641 [418-1047] pg/ml, p < 0.0001). Hydrocortisone use was associated with longer duration of MODS in children with immunoparalysis after adjusting for covariables (aRR 3.7 [1.8-7.9], p = 0.0006) whereas no association with MODS duration was seen in children without immunoparalysis (aRR 1.2 [0.6-2.3], p = 0.67). CONCLUSION: Hydrocortisone use was independently associated with longer duration of MODS in septic children with immunoparalysis but not in those with more robust immune function. Prospective clinical trials using a priori immunophenotyping are needed to understand optimal hydrocortisone strategies in this population.

Risk of bloodstream infection in patients with renal dysfunction: a population-based cohort study.

Although patients with end-stage renal disease (ESRD) are known to be at high risk for developing bloodstream infections (BSI), the risk associated with lesser degrees of renal dysfunction is not well defined. We sought to determine the risk for acquiring and dying from community-onset BSIs among patients with renal dysfunction. A retrospective, population-based cohort study was conducted among adult residents without ESRD in the western interior of British Columbia. Estimated glomerular filtration rates (eGFR) were determined for cases and incidence rate ratios (IRR) were calculated using prevalence estimates. Overall, 1553 episodes of community-onset BSI were included of which 39%, 32%, 17%, 9%, 2% and 1% had preceding eGFRs of ≥90, 60-89, 45-59, 30-44, 15-29 and <15 ml/min/m2, respectively. As compared to those with eGFR ≥60 ml/min/m2, patients with eGFR 30-59 ml/min/m2 (IRR 4.4; 95% confidence interval (CI) 3.9-4.9) and eGFR <30 ml/min/m2 (IRR 7.0; 95% CI 5.0-9.5) were at significantly increased risk for the development of community-onset BSI. An eGFR <30 ml/min/m2 was an independent risk factor for death (odds ratio 2.3; 95% CI 1.01-5.15). Patients with renal dysfunction are at increased risk for developing and dying from community-onset BSI that is related to the degree of dysfunction.

Shock Severity Modifies Associations Between RBC Transfusion in the First 48 Hours of Sepsis Onset and the Duration of Organ Dysfunction in Critically Ill Septic Children.

OBJECTIVE: To test the hypothesis that early RBC transfusion is associated with duration of organ dysfunction in critically ill septic children. DESIGN: Secondary analysis of a single-center prospective observational study. Multivariable negative binomial regression was used to determine relationships between RBC transfusion within 48 hours of sepsis onset and number of days in 14 with organ dysfunction, or with multiple organ dysfunction syndrome. SETTING: A PICU at a quaternary care children's hospital. PATIENTS: Children less than 18 years old with severe sepsis/septic shock by consensus criteria were included. Patients with RBC transfusion prior to sepsis onset and those on extracorporeal membrane oxygenation support within 48 hours of sepsis onset were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-four patients were included. Median age was 6 years (0-13 yr); 61% were male. Seventy-eight percentage had septic shock, and 41 (44%) were transfused RBC within 48 hours of sepsis onset (early RBC transfusion). On multivariable analyses, early RBC transfusion was independently associated with 44% greater organ dysfunction days (adjusted relative risk, 1.44 [1.04-2.]; p = 0.03), although risk differed by severity of illness (interaction p = 0.004) and by shock severity (interaction p = 0.04 for Vasoactive Inotrope Score and 0.03 for shock index). Relative risks for multiple organ dysfunction syndrome days varied by shock severity (interaction p = 0.008 for Vasoactive Inotrope Score and 0.01 for shock index). Risks associated with early RBC transfusion were highest for the children with the lowest shock severities. CONCLUSIONS: In agreement with previous studies, early RBC transfusion was independently associated with longer duration of organ dysfunction. Ours is among the first studies to document different transfusion-associated risks based on clinically available measures of shock severity, demonstrating greater transfusion-associated risks in children with less severe shock. Larger multicenter studies to verify these interaction effects are essential to plan much-needed RBC transfusion trials for critically ill septic children.

Population-based risk factors for community-onset bloodstream infections.

Although a number of comorbidities have been associated with development of bloodstream infection, actual risk factors have not been well defined and quantified in nonselected populations. We sought to quantify population-based risk factors for development of community-onset bloodstream infection (COBSI). Surveillance was conducted among all residents of the Western Interior of British Columbia, Canada, during 2011-2018. Risks were expressed as incidence rate ratios (IRR) with 95% confidence intervals (CI). The annual incidence was 147.1 per 100,000 and older individuals, and males were at overall higher risk. The median Charlson score was 2 (IQR, 0-3), and this was higher among those with healthcare-associated (2; IQR, 1-4) as compared to community-associated (1; IQR, 0-2; P < 0.0001) COBSI. Risk factors for development of COBSI included (IRR; 95% CI): HIV infection (8.89; 5.17-14.27), cancer (6.80; 6.13-7.54), congestive heart failure (4.68; 4.00-5.46), dementia (3.31; 2.82-3.87), diabetes mellitus (3.10; 2.80-3.42), cerebrovascular accident (2.79; 2.34-3.31), renal dysfunction (2.75; 2.33-3.22), chronic lung disease (2.03; 1.79-2.28), peripheral vascular disease (1.68; 1.39-2.01), and rheumatic disease (1.44; 1.14-1.79). Patients with multiple comorbid illnesses were older, more likely to be male, and have healthcare-associated BSI, higher rates of antimicrobial resistance, and different clinical foci of infection. A number of demographic and comorbid conditions significantly increase the risk for development of COBSI.

Occurrence and determinants of Klebsiella species bloodstream infection in the western interior of British Columbia, Canada.

BACKGROUND: Klebsiella species are among the most common causes of bloodstream infection (BSI). However, few studies have evaluated their epidemiology in non-selected populations. The objective was to define the incidence of, risk factors for, and outcomes from Klebsiella species BSI among residents of the western interior of British Columbia, Canada. METHODS: Population-based surveillance was conducted between April 1, 2010 and March 31, 2017. RESULTS: 151 episodes were identified for an incidence of 12.1 per 100,000 population per year; the incidences of K. pneumoniae and K. oxytoca were 9.1 and 2.9 per 100,000 per year, respectively. Overall 24 (16%) were hospital-onset, 90 (60%) were healthcare-associated, and 37 (25%) were community-associated. The median patient age was 71.4 (interquartile range, 58.8-80.9) years and 88 (58%) cases were males. Episodes were uncommon among patients aged < 40 years old and no cases were observed among those aged < 10 years. A number of co-morbid medical illnesses were identified as significant risks and included (incidence rate ratio; 95% confidence interval) cerebrovascular accident (5.9; 3.3-9.9), renal disease 4.3; 2.5-7.0), cancer (3.8; 2.6-5.5), congestive heart failure (3.5; 1.6-6.6), dementia (2.9; 1.5-5.2), diabetes mellitus (2.6; 1.7-3.9), and chronic obstructive pulmonary disease (2.3; 1.5-3.5). Of the 141 (93%) patients admitted to hospital, the median hospital length stay was 8 days (interquartile range, 4-17). The in-hospital and 30-day all cause case-fatality rates were 24/141 (17%) and 27/151 (18%), respectively. CONCLUSIONS: Klebsiella species BSI is associated with a significant burden of illness particularly among those with chronic co-morbid illnesses.

Bloodstream infection due to ß-hemolytic streptococci: a population-based comparative analysis.

PURPOSE: Although the burden of illness due to Streptococcus pyogenes is widely recognized, other ß-hemolytic streptococci are also important causes of invasive infections. The objective of this study was to compare the population-based epidemiology of groups A, B, and C/G ß-hemolytic streptococcal bloodstream infection (BSI). METHODS: Population-based surveillance was conducted in the western interior of British Columbia, Canada, 2011-2018. RESULTS: A total of 210 episodes were identified for an incidence of 14.4 per 100,000; the incidences of groups A, B and C/G streptococcal BSI were 4.2, 4.7, and 5.5 per 100,000, respectively. There was an increasing annual incidence of ß-hemolytic streptococcal BSI from 2011 through to a peak incidence in 2016 that decreased thereafter. Fifty-two percent (110) of BSIs were community associated, 43% (91) were healthcare associated, and 4% (9) were hospital onset. Patients with group A were younger, more likely to be female, and have fewer co-morbidities than patients with groups B and C/G streptococcal BSI. The most common focus of infection was soft tissue (109/52%), followed by primary (33; 16%), and bone and joint (20; 10%) and these varied by streptococcal species (p < 0.001). The 30-day all-cause case fatality rate was 11% (24/210) and did not significantly vary by group (p = 0.7). CONCLUSION: Although the determinants vary, the overall burden of disease related to BSI is similar amongst groups A, B and C/G ß-hemolytic streptococci.

The association of immediate post cardiac arrest diastolic hypertension and survival following pediatric cardiac arrest.

AIM: In-hospital cardiac arrest occurs in >5000 children each year in the US and almost half will not survive to discharge. Animal data demonstrate that an immediate post-resuscitation burst of hypertension is associated with improved survival. We aimed to determine if systolic and diastolic invasive arterial blood pressures immediately (0-20 min) after return of spontaneous circulation (ROSC) are associated with survival and neurologic outcomes at hospital discharge. METHODS: This is a secondary analysis of the Pediatric Intensive Care Quality of CPR (PICqCPR) study of invasively measured blood pressures during intensive care unit CPR. Patients were eligible if they achieved ROSC and had at least one invasively measured blood pressure within the first 20 min following ROSC. Post-ROSC blood pressures were normalized for age, sex and height. "Immediate hypertension" was defined as at least one systolic or diastolic blood pressure >90th percentile. The primary outcome was survival to hospital discharge. RESULTS: Of 102 children, 70 (68.6%) had at least one episode of immediate post-CPR diastolic hypertension. After controlling for pre-existing hypotension, duration of CPR, calcium administration, and first documented rhythm, patients with immediate post-CPR diastolic hypertension were more likely to survive to hospital discharge (79.3% vs. 54.5%; adjusted OR = 2.93; 95%CI, 1.16-7.69). CONCLUSIONS: In this post hoc secondary analysis of the PICqCPR study, 68.6% of subjects had diastolic hypertension within 20 min of ROSC. Immediate post-ROSC hypertension was associated with increased odds of survival to discharge, even after adjusting for covariates of interest.