The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.
Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. to test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (cAp) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (Streptococcus pneumoniae and Staphylococcus aureus) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a + 90% accuracy with LASSO in predicting specific pneumonia etiology. this study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes. Community-acquired pneumonia (CAP) is the leading cause of infectious disease-related death and together with Influenza, the eight-leading cause of death in the USA 1. The annual incidence of CAP worldwide is approximately 5-11 per 1,000 and the estimated annual CAP-associated costs in the US is over 12 billion dollars 2. Even with
Background: Although Clostridioides difficile infections (CDIs) are associated with significant morbidity and mortality, CDI disease burden may be underestimated if a high proportion of inpatients with diarrhea do not have stool specimens collected for CDI diagnostic testing. The objective of this study was to define the frequency of stool specimen collection and testing for CDI in adult hospitalized patients with diarrhea. Methods: A cross-sectional study was conducted in all 9 adult hospitals (total, 3,532 beds) in Louisville (adult aged ≥18 years; population 599,276) to identify patients with diarrhea and to observe the frequency of stool specimen collection for CDI diagnosis. For 7 consecutive days in December 2018, each ward was visited to identify new onset diarrhea (>3 loose stools in 24 hours) among Louisville adults: first via electronic medical record (EMR) review, then by nurse interviews, and finally by interviewing patients. For patients with diarrhea, research staff reviewed EMRs to determine whether a stool specimen was collected for CDI diagnosis, and they interviewed nurses about potential noninfectious causes of diarrhea. Results: Among 2,565 hospitalized adults (with 14,042 patient days), research staff identified 167 patients (47% men; median age, 64 years) with new onset diarrhea, 1.2 diarrhea cases per 100 patient days. Patients with diarrhea were initially ascertained by EMR review (50%), nurse interviews (42%) or patient interviews (8%); all cases identified by patient interviews were identified by nurses the following day (but many cases identified by nurses were never identified by EMR review). Nurses indicated that 67 cases had a potential noninfectious cause of diarrhea (eg, laxatives, feeding tube, colostomy, liquid diet, etc). Stool specimens were collected by hospital staff for CDI testing from 53 of 167 patients (32%) with diarrhea; 10 of 67 patients (15%) with diarrhea for whom nurses reported potential noninfectious causes of diarrhea (laxative use, enteric feeding, or gastric survey) in the past 24 hours; and 43 of 100 patients (43%) with diarrhea with no reported potential noninfectious causes of diarrhea. Stool collection frequency was similar on weekdays and weekends. Conclusions: The low frequency of CDI diagnostic testing of hospitalized patients with diarrhea indicates that CDI may be underdiagnosed in these hospitals and suggests, given that only 32% of patients with diarrhea had a stool specimen collected, that the CDI disease burden may be 3 times larger than currently appreciated. New-onset diarrhea occurred in >1% of patients each day; the most effective method for identifying patients with diarrhea was via nurse interviews.Funding: Pfizer Vaccines supported this study.Disclosures: Frederick Angulo, Kimbal D. Ford, Joann Zamparo, Elisa Gonzalez, Sharon Gray, David Swerdlow, and Catia Ferreira all report salary from Pfizer.
Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality.Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a +90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes. Author SummaryUrine has been classically considered sterile since most microorganisms are not readily culturable under healthy circumstances. Further, many pneumonia patients are immediately placed on antibiotics rendering culture-based techniques useless. However, the advent of next generation sequencing has enabled unprecedented analysis of the microbial communitiesliving or detected as free DNA -found in many niches of the human body. Here, we describe a urine microbiome as well as metabolites and cytokines measured in patients newly admitted to the hospital diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) infection pneumonia, compared with healthy controls. Using these parameters alone, we were able to achieve high success in predicting patient pneumonia. This study provides a proof of concept that urine samples, which are easily accessible in outpatient and inpatient settings, could provide additional diagnostic insights to patient infectious status and future risk factor for complication. Physical Examination and Laboratory FindingsHeart rate (Beats
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