Mortality reduction in severe community-acquired pneumonia: key findings from a large randomized controlled trial and their clinical implications.
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ABSTRACT:
SUBMITTER: Vornicu O
PROVIDER: S-EPMC10632581 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
Publications
Mortality reduction in severe community-acquired pneumonia: key findings from a large randomized controlled trial and their clinical implications.
Vornicu Ovidiu O Perriens Emily E Blackman Sydney S Smoos Elina E Al Sammour Christophe C Oueslati Ilann I Philippot Alexis A Bankier David Vidal DV Haddad Charbel C Bendoumou Maha M François Tom T Michaux Isabelle I Dincq Anne-Sophie AS Evrard Patrick P Bulpa Pierre P Honore Patrick M PM
Annals of translational medicine 20230818 11
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Project description:We aimed to examine the differences in the gene expression profile in peripheral blood at hospital admission between patients with community-acquired pneumonia (CAP) who died and survived during hospitalization. Whole blood samples for genome expression profile analysis were obtained within 24 hours of hospital admission. Gen set enrichment analysis (GSEA) identified gene sets positively enriched in the patients who survived, mainly related with interferon- alpha response, apoptosis, and sex hormones pathways. Similarly, GSEA identified gene sets positively enrichment for the patients who died (oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways).
2022-10-17 | GSE188309 | GEO
Project description:Prediction of patient-centered outcomes in hospitals is useful for performance benchmarking, resource allocation, and guidance regarding active treatment and withdrawal of care. Yet, their use by clinicians is limited by the complexity of available tools and amount of data required. We propose to use Disjunctive Normal Forms as a novel approach to predict hospital and 90-day mortality from instance-based patient data, comprising demographic, genetic, and physiologic information in a large cohort of patients admitted with severe community acquired pneumonia. We develop two algorithms to efficiently learn Disjunctive Normal Forms, which yield easy-to-interpret rules that explicitly map data to the outcome of interest. Disjunctive Normal Forms achieve higher prediction performance quality compared to a set of state-of-the-art machine learning models, and unveils insights unavailable with standard methods. Disjunctive Normal Forms constitute an intuitive set of prediction rules that could be easily implemented to predict outcomes and guide criteria-based clinical decision making and clinical trial execution, and thus of greater practical usefulness than currently available prediction tools. The Java implementation of the tool JavaDNF will be publicly available.
| S-EPMC3974677 | biostudies-literature
Project description:Community-acquired pneumonia is a significant clinical and public health problem. Defining and predicting severe pneumonia is difficult but important.Several new predictive models and more sophisticated approaches to describing pneumonia severity have been recently proposed, with subsequent validation in varied patient populations. Early data suggest that biomarkers may be useful in the future.Definitions of pneumonia severity depend on the relevant clinical or public health question. A health services reference definition seems most useful in most settings. The Infectious Disease Society of America/American Thoracic Society 2007 guidelines and SMART-COP are two recent promising methods for predicting severe pneumonia at the time of presentation. The traditional pneumonia severity index and Confusion Uremia Respiratory rate Blood pressure (CURB)-65 models are less useful. Accurate assessment of severity has important implications for triage, outcome, and defining populations for research applications. Novel biomarkers, while somewhat promising, do not yet have a validated role in pneumonia severity assessment.
| S-EPMC2875269 | biostudies-literature
Project description:Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07-1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50-2.04) and renal disease (OR, 1.57; 95% CI, 1.21-2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52-0.73). Bacteremia (OR, 1.37; 95% CI, 1.05-1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31-1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10-2.49) were associated with severe sepsis CAP.CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.
| S-EPMC4699794 | biostudies-other
Project description:The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI?<?91 points) or severe (PSI???91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response.
| S-EPMC7087758 | biostudies-literature
Project description:BackgroundAssessment of early response to treatment is crucial for the management of community-acquired pneumonia (CAP).ObjectiveTo describe the predictors and the outcomes of early clinical stability.MethodsWe did a secondary analysis of a multicentre randomized controlled trial on CAP treatment in which 580 patients hospitalized for moderately severe CAP were included. The association between demographic, clinical and biological variables available at inclusion and early clinical stability (stabilization of vital signs within 72 hours with predetermined cut-offs) was assessed by multivariate logistic regression. The association between early clinical stability and mortality, severe adverse events, and length of stay was also tested.ResultsYounger age (OR 0.98, 95% CI 0.96-0.99), lower platelet count (OR per 10 G/L increment 0.96, 95% CI 0.94-0.98), lower respiratory rate (OR 0.94, 95% CI 0.90-0.97), absence of hypoxemia (OR 0.58, 95% CI 0.40-0.85), lower numbers of co-morbid conditions (OR 0.82, 95% CI 0.69-0.98) and signs or symptoms (OR 0.78, 95% CI 0.68-0.90) were significantly associated with early clinical stability. Patients with early clinical stability had lower 90-days mortality (3.4% vs. 11.9%, p<0.001), fewer admissions to the intensive care unit (2.7% vs. 8.0%, p = 0.005) and a shorter length of stay (6.0 days, IQR 4.0-10.0 vs. 10.0 days, IQR 7.0-15.0, p<0.001).ConclusionsPatients with younger age, less co-morbidity, fewer signs or symptoms, less respiratory compromise, and a lower platelet count are more likely to reach early clinical stability. Patients without early clinical stability have a worse prognosis and warrant close scrutiny.
| S-EPMC4909239 | biostudies-literature
Project description:ObjectivesCompare the clinical practice and outcomes in severe community-acquired pneumonia (sCAP) patients to those in non-sCAP patients using guideline-defined criteria for sCAP.DesignRetrospective observational cohort study.SettingOne hundred seventy-seven U.S. hospitals within the Premier Healthcare Database.PatientsHospitalized adult (≥ 18 yr old) patients with pneumonia.Measurements and main resultsAdult patients (≥ 18 yr old) with a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia paired with a principal diagnosis of sepsis or respiratory failure were included. Patients with at least one guideline-defined major criterion for severe pneumonia were compared with patients with nonsevere disease. Among 154,799 patients with pneumonia, 21,805 (14.1%) met criteria for sCAP. They had higher organ failure scores (1.9 vs 0.63; p < 0.001) and inpatient mortality (22.0 vs 5.0%; p < 0.001), longer lengths of stay (8 vs 5 d; p < 0.001), and higher costs ($20,046 vs $7,543; p < 0.001) than those with nonsevere disease. Patients with sCAP had twice the rate of positive blood cultures (10.0% vs 4.5%; p < 0.001) and respiratory cultures (34.2 vs 21.1%; p < 0.001) and more often had isolates resistant to first-line community-acquired pneumonia antibiotics (10% of severe vs 3.1% of nonsevere; p < 0.001). Regardless of disease severity, Streptococcus pneumoniae was the most common pathogen recovered from blood cultures and Staphylococcus aureus and Pseudomonas species were the most common pathogens recovered from the respiratory tract. Although few patients with sCAP had cultures positive for a resistant organism, 65% received vancomycin and 42.8% received piperacillin-tazobactam.ConclusionssCAP patients had worse outcomes and twice the rate of culture positivity. S. aureus and S. pneumoniae were the most common organisms in respiratory and blood specimens, respectively. Although only recommended for sCAP patients, nearly all pneumonia patients received blood cultures, a quarter of nonsevere patients received sputum cultures, and treatment with broad-spectrum agents was widespread, indicating fertile ground for antimicrobial and diagnostic stewardship programs.
| S-EPMC9233133 | biostudies-literature
Project description:To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America.A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia.In the case of community acquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions.The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions.
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Project description:We report a case of community-acquired pneumonia in a patient in China. We verified Legionella pneumophila infection through next-generation sequencing of blood, sputum, and pleural effusion samples. Our results show the usefulness of next-generation sequencing and of testing different samples early in the course of illness to identify this bacterium.
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Project description:Pneumonia is the fourth leading cause of death globally, and the reason for the high mortality rate of patients with severe community-acquired pneumonia (SCAP) remains elusive. Corticosteroid treatment reduces mortality in adults with SCAP but can cause numerous adverse events. Therefore, novel therapeutic targets need to be explored and new adjunctive immune drugs are urgently required. We analyzed the transcriptome data of peripheral blood leukocytes from patients with SCAP and healthy controls from three perspectives: differentially expressed genes, predicted functions of differentially expressed long non-coding RNAs, and transcriptional read-through. We discovered that the NETosis pathway was top-ranked in patients with SCAP caused by diverse kinds of pathogens. This provides a potential therapeutic strategy for treating patients. Furthermore, we calculated the correlation between the expression of genes involved in NETosis and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified four novel potential therapeutic targets for NETosis in patients with SCAP, including H4C15, H3-5, DNASE1, and PRKCB. In addition, a higher occurrence of transcriptional read-through is associated with a worse outcome in patients with SCAP, which probably can explain the high mortality rate of patients with SCAP.
| S-EPMC9709478 | biostudies-literature