Severe Community-acquired Pneumonia Research Articles

Clinical and bacteriological profile of community acquired pneumonia in hospitalized children

Community-acquired pneumonia (CAP) is the leading cause of mortality and morbidity with important clinical impact across the World. India accounts for 23 per cent of global pneumonia burden with case fatality rates between 14 and 30 per cent. Pneumonia is basically classified into typical and atypical pneumonia. Emerging evidence indicates that dual typical and atypical bacterial infections function synergistically in many cases and together likely enhance the severity of CAP. However, the optimal management of CAP in children is still not well defined and the diagnosis is challenging when based solely on clinical observations since the common symptoms of CAP, especially at an early stage, are similar to those of ordinary respiratory tract infections. So RT-PCR is a rapid and precise molecular technique is used for rapid detection of bacteria causing community acquired pneumonia. A total of 268 samples were tested for the respective bacterial pathogens, among the tested the most common pathogen was Haemophilus influenzae (18.3%, 49/268) followed by S. pneumoniae (14.6%,39/268), M. catarhallis (9.3%,25/268),M. pneumoniae (9%, 24/268), B. parapertusis (3.4%,9/268), B. pertusis (1.5%, 4/268), C. pneumoniae (1.5%, 4/268), C. burnetti (1.1%, 3/268)and L. pneumophila (0.74%, 2/268). H. influenza and S. pneumoniae were the most commonly detected organisms among the community acquired pneumonia patients.

Systemic Corticosteroids for Treating Respiratory Diseases: Less Is Better, but… When and How Is It Possible in Real Life?

Systemic corticosteroids (CSs), a keystone in pulmonology, are drugs with strong antiinflammatory activity. They are cheap, easily available, and accessible, but with common and serious side effects. Moreover, the use of exogenous CSs may suppress the hypothalamic-pituitary-adrenal (HPA) axis, predisposing to adrenal insufficiency. Safe CS treatment is a challenge of pharmacological research. This narrative review examined the indications of CSs in some respiratory diseases, analyzing what types, dosages, and length of treatment are required as the dosage and duration of CS treatments need to be minimized. Chronic maintenance treatments with CSs are associated with poor prognosis, but they are still prescribed in patients with severe asthma, Chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. When CS discontinuation is not possible, all efforts should be made to achieve clinically meaningful reductions. Guidelines suggest the use of methylprednisolone at a dose of 20-40mg/day or equivalent for up to 10days in subjects with COVID-19 pneumonia (but not other respiratory viral diseases) and respiratory failure, exacerbations of asthma, and COPD. Some guidelines suggest that CS treatment shorter than 10-14days can be abruptly stopped, strictly monitoring subjects with unexplained symptoms after CS withdrawal, who should promptly be tested for adrenal insufficiency (AI) and eventually treated. CSs are often used in severe community-acquired pneumonia associated with markedly increased serum inflammation markers, in acute respiratory distress syndrome (ARDS), in septic shock unresponsive to hydro-saline replenishment and vasopressors, and acute exacerbations of interstitial lung diseases. As these cases often require higher doses and longer duration of CS treatment, CS tapering should be gradual and, when useful, supported by an evaluation of HPA axis function.

Association of Chest Radiography With Outcomes in Pediatric Pneumonia: A Population-Based Study.

Chest radiograph (CXR) is often performed for the evaluation of community-acquired pneumonia (CAP) in the ED setting. We sought to evaluate the association of undergoing CXR with 7-day hospitalization after emergency department (ED) discharge among patients with CAP. This was a retrospective cohort study including children 3 months to 17 years discharged from any ED within 8 states from 2014 to 2019. We evaluated the association of CXR performance with 7-day hospitalization at both the patient and ED levels using mixed-effects logistic regression models accounting for markers of illness severity. Secondary outcomes included 7-day ED revisits and 7-day hospitalization with severe CAP. Among 206 694 children with CAP, rates of 7-day ED revisit, hospitalization, and severe CAP were 8.9%, 1.6%, and 0.4%, respectively. After adjusting for illness severity, CXR was associated with fewer 7-day hospitalizations (1.6% vs. 1.7%, adjusted odds ratio: [aOR] 0.82, 95% confidence interval [CI]: 0.73-0.92). CXR performance varied somewhat between EDs (median 91.5%, IQR: 85.3%-95.0%). EDs in the highest quartile had fewer 7-day hospitalizations (1.4% vs 1.9%, aOR: 0.78, 95% CI: 0.65-0.94), ED revisits (8.5% vs 9.4%, aOR: 0.88, 95% CI: 0.80-0.96) and hospitalizations for severe CAP (0.3% vs. 0.5%, aOR: 0.70, 95% CI: 0.51-0.97) as compared to EDs with the lowest quartile of CXR utilization. Among children discharged from the ED with CAP, performance of CXR was associated with a small but significant reduction in hospitalization within 7 days. CXR may be helpful in the prognostic evaluation of children with CAP discharged from the ED.

P01 Antibiotic efficacy treatment of community-acquired pneumonia among CMV-infected individuals

Abstract Background The investigation is devoted to possible antibiotic resistance formation and its adverse event prognostic influence among young patients with community-acquired pneumonia (CAP) with cytomegalovirus (CMV) persistence and absence of other comorbid pathology. Subjects and methods The observation included 105 patients (average age 34.1 ± 0.8 years), which had been examined by epidemiological, clinical (including PORT prognostic scale) according to European Respiratory Society requirements, serological test for CMV IgM, IgG detection and antibiotic usage questionnaire for a 3-month period prior CAP. Results 76.2% (n = 80) CAP patients had positive CMV IgG. CMV-positive patients were characterized by higher severity outcome risk in the nearest future versus CMV-negative ones (P < 0.0001): third risk class—14.9 times higher, fourth risk class—10.5 times higher. CMV IgG–positive results correlated with the CAP severity level (r (Spearman) = 0.472). In total, 51.4% (n = 54, among them 47 CMV-positive patients) mentioned antibiotic use during the last 3 months prior to CAP. During the CAP treatment, 75.0% (n = 60) of CMV-positive patients and 20.0% (n = 5) of CMV-negative ones did not respond to antibiotic treatment by cephalosporin and quinolone lines and needed changes in aetiology prescription according to antibiotic susceptibility microbial test. 61.3% (n = 47) of CAP patients (everybody was after medication replacement) got adverse events like antibiotic-associated diarrhoea (16 cases), QT prolongation in ECG (17 cases), creatinine, urea elevation (11 cases) and alanine/aminotransferase elevation (5 cases). Conclusions CMV persistence is associated with higher risk of severe CAP among young patients without comorbid pathologies and contributes to the antibiotic resistance creation as well as related side effects.

Nonlinear main components of the cytokine profile in children with community-acquired pneumonia

Cytokines are the key mediators which control and regulate immune and inflammatory responses via complex networks and serve as biomarkers of many diseases. Quantitative determination of cytokines is helpful in assessing immune status and adjusting therapy for various inflammatory diseases, such as sepsis and pneumonia. Since community-acquired pneumonia remains a common cause of childhood morbidity and mortality. At the present stage, prognosis of the disease severity in children is an urgent problem. The aim of our study was to identify associations between cytokine levels in healthy children and in children with community-acquired pneumonia (CAP), depending on the age of patients and severity of the pathological process. The work was carried out at the Department of Microbiology, Virology and Immunology, Department of Propaedeutics of Childhood Diseases and Pediatrics, and at the Research Institute of Immunology at the South Ural State Medical University. The study included 117 children aged 1 to 18 years with radiologically confirmed diagnosis of CAP, either severe or mild degree. The comparison group was composed from 28 healthy children who did not have community-acquired pneumonia, as well as other signs of acute respiratory viral infection at the time of examination, being observed for any chronic disorders. The levels of IL-1β, IFNγ, IL-6, IL-4, IL-10, IL-2, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF were determined in blood serum by means of ELISA test systems (a “sandwich” technique with peroxidase as an indicator enzyme). For statistical analysis, a multidimensional method was used, i.e., non-linear analysis of the principal components using the CATPCA algorithm. Among the children with CAP, our study revealed a consistent increase of IL-1ß, IL-4, IL-10, IL-2, TNFα, IFNλ2 (IL-28A), IFNλ3 (IL-28B), IL-8, MCP-1, IL-17AF, GM-CSF in blood serum. The highest correlation with severity was shown for IFNλ2 (IL-28A), IFNλ3 (IL-28B) and MCP-1, which may be considered additional biomarkers of the CAP severity. There was also a significant variability of the cytokine profile in healthy children and its significant skewing in pneumonia, especially in severe cases.

Diagnostic and prognostic value of deregulated long non-coding RNA RPPH1 in patients with severe community-acquired pneumonia: a retrospective cohort study

BackgroundSevere community-acquired pneumonia (SCAP) is one of the most common critical and acute diseases in the respiratory and acute medicine department. The expression and significance of lncRNA RPPH1 (RPPH1) in SCAP were assessed aiming to explore a biomarker assisting in the screening and management of SCAP.MethodsThis study is a retrospective study enrolled 97 SCAP patients, 102 mild community-acquired pneumonia (MCAP) patients, and 65 healthy individuals. The serum expression of RPPH1 of study subjects was evaluated using PCR. The diagnostic and prognostic significance of RPPH1 in SCAP was evaluated by ROC and Cox analyses. Meanwhile, the correlation of RPPH1 with patients’ clinicopathological features was evaluated by spearman correlation analysis to evaluate its role in assessing disease severity.ResultsA significant downregulation of RPPH1 was observed in the serum of SCAP patients compared with MCAP and healthy individuals. RPPH1 was positively correlated with ALB (r = 0.74) and negatively correlated with C-reactive protein (r = -0.69), neutrophil-to-lymphocyte ratio (r = -0.88), procalcitonin (r = -0.74), and neutrophil (r = -0.84) of SCAP patients, which are associated with the development and severity of SCAP. Additionally, reduced RPPH1 was closely associated with the 28-day development-free survival of SCAP patients and served as an adverse prognostic indicator together with procalcitonin.ConclusionsDownregulated RPPH1 in SCAP could act as a diagnostic biomarker screening SCAP from healthy and MCAP individuals and act as a prognostic biomarker predicting patients’ disease conditions and outcomes. The demonstrated significance of RPPH1 in SCAP could assist the clinical antibiotic therapies of SCAP patients.

Machine learning-based identification of cuproptosis-related markers and immune infiltration in severe community-acquired pneumonia.

Severe community-acquired pneumonia (SCAP) is one of the world's most common diseases and a major etiology of acute respiratory distress syndrome (ARDS). Cuproptosis is a novel form of regulated cell death that can occur in various diseases. Our study explored the degree of immune cell infiltration during the onset of severe CAP and identified potential biomarkers related to cuproptosis. Gene expression matrix was obtained from GEO database indexed GSE196399. Three machine learning algorithms were applied: The least absolute shrinkage and selection operator (LASSO), the random forest, and the support vector machine-recursive feature elimination (SVM-RFE). Immune cell infiltration was quantified by single-sample gene set enrichment analysis (ssGSEA) scoring. Nomogram was constructed to verify the applicability of using cuproptosis-related genes to predict the onset of severe CAP and its deterioration toward ARDS. Nine cuproptosis-related genes were differentially expressed between the severe CAP group and the control group: ATP7B, DBT, DLAT, DLD, FDX1, GCSH, LIAS, LIPT1, and SLC31A1. All 13 cuproptosis-related genes were involved in immune cell infiltration. A three-gene diagnostic model was constructed to predict the onset of severe CAP: GCSH, DLD, and LIPT1. Our study confirmed the involvement of the newly discovered cuproptosis-related genes in the progression of SCAP.

Survival status and predictors of mortality from severe community-acquired pneumonia among under-five children admitted at Debre Tabor comprehensive specialized hospital: a prospective cohort study.

Globally, Pneumonia continues to be the leading cause of mortality among under-five children. Ethiopia ranks fourth out of 15 countries worldwide in terms of the highest death rate of under-five children due to severe community-acquired pneumonia (SCAP). However, to date, there is no recent study that shows survival status and predictors of mortality from SCAP. Therefore, this study aimed to determine survival status and predictors of mortality from this dangerous disease among under-five children. A facility-based prospective cohort study was conducted from 1 November 2021 to 31 October 2022 at Debre Tabor comprehensive specialized hospital. All under-five children with SCAP admitted during the study period were included. Participants were selected using a systematic sampling technique. The collected data were coded, edited, and entered into epi-data version 4.2 and then exported to STATA version 17 for further analysis. The Kaplan Meier failure estimate with log-rank test was employed to determine the survival estimates. A cox-proportional hazard regression model was fitted to identify significant variables. The overall incidence density rate of mortality was 5.7 /1000 children with a median hospital stay of 8.2 days. Heart disease (AHR: 4.37; 95%CI: 1.68-11.32), previous admission of SCAP (AHR: 3.87; 95% CI: 1.31-11.43), WFL < -3Z score (AHR: 3.57; 95% CI: 1.02-12.42), impaired consciousness level at admission 3.41(1.14-10.19), and pleural effusion (AHR: 3.42; 95%CI: 1.18-9.93) were significant predictors of mortality. In this study, the survival probability of children with SCAP was low. Children with heart disease, previous admission of SCAP, WFL < -3Z score, impaired consciousness level at admission, and pleural effusion had low survival. Therefore, much emphasis is needed on children with SCAP, particularly those with identified predictors.

Novel protein biomarkers for pneumonia and acute exacerbations in COPD: a pilot study.

Community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) result in high morbidity, mortality, and socio-economic burden. The usage of easily accessible biomarkers informing on disease entity, severity, prognosis, and pathophysiological endotypes is limited in clinical practice. Here, we have analyzed selected plasma markers for their value in differential diagnosis and severity grading in a clinical cohort. A pilot cohort of hospitalized patients suffering from CAP (n = 27), AECOPD (n = 10), and healthy subjects (n = 22) were characterized clinically. Clinical scores (PSI, CURB, CRB65, GOLD I-IV, and GOLD ABCD) were obtained, and interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-2-receptor (IL-2R), lipopolysaccharide-binding protein (LBP), resistin, thrombospondin-1 (TSP-1), lactotransferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil-elastase-2 (ELA2), hepatocyte growth factor (HGF), soluble Fas (sFas), as well as TNF-related apoptosis-inducing ligand (TRAIL) were measured in plasma. In CAP patients and healthy volunteers, we found significantly different levels of ELA2, HGF, IL-2R, IL-6, IL-8, LBP, resistin, LTF, and TRAIL. The panel of LBP, sFas, and TRAIL could discriminate between uncomplicated and severe CAP. AECOPD patients showed significantly different levels of LTF and TRAIL compared to healthy subjects. Ensemble feature selection revealed that CAP and AECOPD can be discriminated by IL-6, resistin, together with IL-2R. These factors even allow the differentiation between COPD patients suffering from an exacerbation or pneumonia. Taken together, we identified immune mediators in patient plasma that provide information on differential diagnosis and disease severity and can therefore serve as biomarkers. Further studies are required for validation in bigger cohorts.

Associations between indicators of new semi-quantitative express-test for procalcitonin and indicators of saturation in patients with community-acquired pneumonia

Objective. To evaluate the associations between the indicators of a new semi-quantitative express-test for procalcitonin and saturation levels in hospitalized patients with community-acquired pneumonia.&#x0D; Due to a high rate of growth of the incidence of severe community-acquired pneumonia, which leads to disability of the working population and claims thousands of lives, there is a need for early verification of the severity degree and a timely initiation of treatment. Traditional clinical, radiologic, laboratory and bacteriological criteria for inflammatory reactions (fever, increased pulmonary infiltration and leukocytosis, detection of potential pathogens in sputum or hemocultures) are not specific for pneumonia. Similar clinical and radiologic manifestations can also be noted in other pathological conditions, for example, in atelectasis of the lung, lung infarction, congestive heart failure, as well as acute respiratory distress syndrome. In this regard, the study of new diagnostic markers of community-acquired pneumonia is an actual direction in modern therapeutic diagnostics. Being a fast and highly sensitive method, the express test for procalcitonin can be a valuable predictive marker for the severe course of community-acquired pneumonia. Of interest is the relationship of procalcitonin with an indicator reflecting the presence of respiratory failure the level of saturation.&#x0D; Materials and methods. A single-stage comparative study involved 123 patients admitted to the hospital with a confirmed diagnosis of community-acquired pneumonia. On the first day after admission to the hospital, all patients underwent a general clinical examination, an overview X-ray of the chest organs, and determination of the plasma procalcitonin level using a semi-quantitative express-test as well as the saturation level. According to the results of the examination, the patients were divided into two groups: patients with saturation 94 % (n=43), and patients with saturation 94 % (n=80). The group of patients with saturation values 94 % consisted of 23 (53.5 %) women and 20 (46.5 %) men. The group of patients with saturation values 94 % consisted of 42 (52.5 %) women and 38 (47.5 %) men. The mean age of the patients was 56.719.1 and 45.620.7 (MSD) years, respectively, p=0.005. Statistical processing of the obtained data was carried out using the SPSS 13.0 software package.&#x0D; Results. Patients with low saturation values ( 94 %) had higher heart rate (p=0.001) and respiratory rate (p=0.001), and the levels of erythrocytes (p=0.001), hemoglobin (p=0.003) and albumin (p=0.001) were significantly lower than in patients with higher saturation levels 94 %. For patients with signs of respiratory failure and saturation indices 94 %, a more pronounced increase in the level of express-test for procalcitonin was characteristic (p=0.001). According to regression analysis, the express-test for procalcitonin 2 ng/ml by 13.8 % (CI 1.5131.3), age by 3 %, and heart rate by 11 % increase the risk of low saturation in patients with community-acquired pneumonia.&#x0D; Conclusion. Low values of blood oxygen saturation 94 % in hospitalized patients with community-acquired pneumonia are directly associated with high values of the new semi-quantitative express-test for procalcitonin (more than 2 ng/ml), that can be used for individual risk stratification.

Risk Factors and outcomes associated with inappropriate empiric broad-spectrum antibiotic use in hospitalized patients with community-acquired pneumonia

Background: Inappropriate broad-spectrum antibiotic use targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa can result in increased adverse events, antibiotic resistance, and Clostridioides difficile infection. In 2019, revised ATS/IDSA community-acquired pneumonia (CAP) guidelines removed healthcare-associated pneumonia (HCAP) as a clinical entity and modified patient factors warranting empiric broad-spectrum antibiotic (BSA) use. As a result, most patients hospitalized with CAP should receive empiric antibiotics targeting standard CAP pathogens. Based on revised guidelines, we evaluated predictors and outcomes associated with inappropriate BSA use among hospitalized patients with CAP. Methods: Between November 2019 and July 2022, trained abstractors collected data on non-ICU adult medical patients admitted with CAP at 67 Michigan hospitals who received either an inappropriate empiric BSA on hospital day 1 or 2 or a standard CAP regimen. Inappropriate empiric BSA use was defined as use of an anti-MRSA or anti-pseudomonal antibiotic in a patient eligible for standard CAP coverage per IDSA guidelines. Patients with immune compromise, moderate or severe chronic obstructive pulmonary disease (COPD), pulmonary complication, or guideline-concordant treatment with BSA were excluded. Data collected included comorbidities, antibiotic use and hospitalizations in the preceding 90 days, cultures in the preceding year, signs or symptoms of pneumonia, hospital characteristics, and 30-day postdischarge patient outcomes. Data were collected through chart review and patient phone calls. Predictors of inappropriate empiric BSA were evaluated using logistic general estimating equation (GEE) models, accounting for hospital-level clustering. We assessed the effect of inappropriate empiric BSA (vs standard CAP therapy) on 30-day patient outcomes using logistic GEE models controlling for predictors associated with the outcome and probability of treatment. Results: Of 8,286 included patients with CAP, 2,215 (26.7%) were empirically treated with inappropriate BSA. The median BSA treatment was 3 days (IQR, 2.5). After adjustments, factors associated with inappropriate empiric BSA treatment included hospitalization or treatment with high-risk antibiotics in preceding 90 days, transfer from a postacute care facility, hemodialysis, support with ≥3 L supplemental oxygen, severe sepsis, leukocytosis, and higher pneumonia severity index (Fig. 1). After adjustments, patients with inappropriate empiric BSA treatment had higher readmissions 30 days after discharge, more transfers to the intensive care unit, more antibiotic-associated adverse events, and longer hospitalizations (Fig. 2). Conclusions: Patients hospitalized with CAP often received inappropriate BSA as empiric coverage, and this inappropriate antibiotic selection was associated with worse patient outcomes. To improve patient outcomes, stewardship efforts should focus on reducing inappropriate BSA use in patients hospitalized for CAP with historic HCAP risk factors or severe CAP without other guideline-directed indications for BSA.Financial support. H.M.S. initiative is underwritten by Blue Cross and Blue Shield of Michigan.Disclosures: None

Corticosteroids in ARDS.

Acute respiratory distress syndrome (ARDS) is frequently associated with sepsis. ARDS and sepsis exhibit a common pathobiology, namely excessive inflammation. Corticosteroids are powerful anti-inflammatory agents that are routinely used in septic shock and in oxygen-dependent SARS-CoV-2 related acute respiratory failure. Recently, corticosteroids were found to reduce mortality in severe community-acquired pneumonia. Corticosteroids may therefore also have a role to play in the treatment of ARDS. This narrative review was undertaken following a PubMed search for English language reports published before January 2023 using the terms acute respiratory distress syndrome, sepsis and steroids. Additional reports were identified by examining the reference lists of selected articles and based on personnel knowledge of the authors of the field. High-quality research is needed to fully understand the role of corticosteroids in the treatment of ARDS and to determine the optimal timing, dosing and duration of treatment.

Generation of Human Embryonic Stem Cell-Derived Lung Organoids for Modeling Infection and Replication Differences between Human Adenovirus Types 3 and 55 and Evaluating Potential Antiviral Drugs.

Human adenoviruses type 3 (HAdV-3) and type 55 (HAdV-55) are frequently encountered, highly contagious respiratory pathogens with high morbidity rate. In contrast to HAdV-3, one of the most predominant types in children, HAdV-55 is a reemergent pathogen associated with more severe community-acquired pneumonia (CAP) in adults, especially in military camps. However, the infectivity and pathogenicity differences between these viruses remain unknown as in vivo models are not available. Here, we report a novel system utilizing human embryonic stem cells-derived 3-dimensional airway organoids (hAWOs) and alveolar organoids (hALOs) to investigate these two viruses. Firstly, HAdV-55 replicated more robustly than HAdV-3. Secondly, cell tropism analysis in hAWOs and hALOs by immunofluorescence staining revealed that HAdV-55 infected more airway and alveolar stem cells (basal and AT2 cells) than HAdV-3, which may lead to impairment of self-renewal functions post-injury and the loss of cell differentiation in lungs. Additionally, the viral life cycles of HAdV-3 and -55 in organoids were also observed using Transmission Electron Microscopy. This study presents a useful pair of lung organoids for modeling infection and replication differences between respiratory pathogens, illustrating that HAdV-55 has relatively higher replication efficiency and more specific cell tropism in human lung organoids than HAdV-3, which may result in relatively higher pathogenicity and virulence of HAdV-55 in human lungs. The model system is also suitable for evaluating potential antiviral drugs, as demonstrated with cidofovir. IMPORTANCE Human adenovirus (HAdV) infections are a major threat worldwide. HAdV-3 is one of the most predominant respiratory pathogen types found in children. Many clinical studies have reported that HAdV-3 causes less severe disease. In contrast, HAdV-55, a reemergent acute respiratory disease pathogen, is associated with severe community-acquired pneumonia in adults. Currently, no ideal in vivo models are available for studying HAdVs. Therefore, the mechanism of infectivity and pathogenicity differences between human adenoviruses remain unknown. In this study, a useful pair of 3-dimensional (3D) airway organoids (hAWOs) and alveolar organoids (hALOs) were developed to serve as a model. The life cycles of HAdV-3 and HAdV-55 in these human lung organoids were documented for the first time. These 3D organoids harbor different cell types, which are similar to the ones found in humans. This allows for the study of the natural target cells for infection. The finding of differences in replication efficiency and cell tropism between HAdV-55 and -3 may provide insights into the mechanism of clinical pathogenicity differences between these two important HAdV types. Additionally, this study provides a viable and effective in vitro tool for evaluating potential anti-adenoviral treatments.

Non-invasive respiratory support in patients with severe community-acquired pneumonia

Acute respiratory failure (ARF) is the leading cause of death in hospitalized patients with severe forms of COVID-19. At the beginning of COVID-19 pandemic the starting respiratory protocol suggested early use of intubation and artificial lung ventilation (ALV) in patients with severe pneumonia complicated by ARF. However, after the analysis of the published studies it was noted that the pathophysiology of the development of ARF in COVID-19 had features that determine the atypical clinical pattern – “silent hypoxemia”. This leads to the late onset of respiratory support (RS) and, as a result, to the lower effectiveness of non-invasive RS methods. This article discusses the creation of an algorithm for the early use of various non-invasive RS methods in patients with COVID-19 complicated by ARF, that will decrease the frequency of hospitalization to the Intensive care units, tracheal intubation and ALV, reduce the duration of treatment and improve prognosis.

Corticosteroids in Community-Acquired Bacterial Pneumonia: a Systematic Review, Pairwise and Dose-Response Meta-Analysis.

International guidelines provide heterogenous guidance on use of corticosteroids for community-acquired pneumonia (CAP). We performed a systematic review of randomized controlled trials examining corticosteroids in hospitalized adult patients with suspected or probable CAP. We performed a pairwise and dose-response meta-analysis using the restricted maximum likelihood (REML) heterogeneity estimator. We assessed the certainty of the evidence using GRADE methodology and the credibility of subgroups using the ICEMAN tool. We identified 18 eligible studies that included 4661 patients. Corticosteroids probably reduce mortality in more severe CAP (RR 0.62 [95% CI 0.45 to 0.85]; moderate certainty) with possibly no effect in less severe CAP (RR 1.08 [95% CI 0.83 to 1.42]; low certainty). We found a non-linear dose-response relationship between corticosteroids and mortality, suggesting an optimal dose of approximately 6 mg of dexamethasone (or equivalent) for a duration of therapy of 7 days (RR 0.44 [95% 0.30 to 0.66]). Corticosteroids probably reduce the risk of requiring invasive mechanical ventilation (RR 0.56 [95% CI 0.42 to 74] and probably reduce intensive care unit (ICU) admission (RR 0.65 [95% CI 0.43 to 0.97]) (both moderate certainty). Corticosteroids may reduce the duration of hospitalization and ICU stay (both low certainty). Corticosteroids may increase the risk of hyperglycemia (RR 1.76 [95% CI 1.46 to 2.14]) (low certainty). Moderate certainty evidence indicates that corticosteroids reduce mortality in patients with more severe CAP, the need for invasive mechanical ventilation, and ICU admission.

Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study

BackgroundCommunity-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents.MethodsA multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated.ResultsAmong the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06–92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP.ConclusionsThe major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Changes in the pathogen spectrum of hospitalized adults with community-acquired pneumonia in Fujian Province: A multicenter, retrospective study from 2012 to 2018.

Changes in the pathogen spectrum of hospitalized adults with community-acquired pneumonia in Fujian Province: A multicenter, retrospective study from 2012 to 2018.

Low Mortality among Under-5 Children with Severe Community-Acquired Pneumonia: A 5-Year Retrospective Analysis of 588 Admissions in Ibadan, Nigeria

Abstract Objective Community-acquired pneumonia (CAP) is the commonest cause of death in under-5 children worldwide. Although the mortality from CAP has decreased over the last decade, it is still unacceptably high in lower-middle-income countries (LMICs). We aimed to determine the case fatality rate (CFR), and factors associated with treatment failure and outcome, using recommended antimicrobials. Methods A 5-year retrospective review of severe pediatric pneumonia admissions between August 1st, 2014 and July 31st, 2019 at the University College Hospital, Ibadan, Nigeria was conducted. Relevant clinical information including antibiotics use and outcome was analyzed using descriptive statistics, test of association, and logistic regression. Results There were 588 children aged 2 to 59 months, male:female ratio was 1.5:1. About two-thirds were aged ≤12 months. The majority were fully immunized for age (87.2%), about 34% were malnourished and 68% were hypoxemic at presentation. Only 71% of children were commenced on the recommended first-line antibiotics following the Pediatric Association of Nigeria (PAN) antibiotic guidelines. Initial antibiotics were changed in 22.3% of the patients. The need to change intravenous (iv) amoxicillin plus iv gentamicin was necessary in 23.80% compared with 18.1% for iv cefuroxime plus iv gentamicin. Severe acute malnutrition (odds ratio [OR]: 2.8 [95% confidence interval [CI]: 1.1–7.3]) and hypoxemia (OR:2.3 [95%CI: 1.0–5.6]) were independently associated with antibiotics change. The CFR was 1.36%. Conclusion The low CFR suggests a better outcome compared with other previous studies in LMICs. However, the high rate of antibiotics changes (22.3%) was possibly due to failure of first line antibiotics; especially among malnourished and hypoxemic children. Randomized controlled trial of iv cefuroxime plus gentamicin versus iv amoxicillin plus gentamicin is recommended.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia.

Severe community-acquired pneumonia (sCAP) is associated with high morbidity and mortality, and whilst European and non-European guidelines are available for community-acquired pneumonia, there are no specific guidelines for sCAP. The European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and Latin American Thoracic Association (ALAT) launched a task force to develop the first international guidelines for sCAP. The panel comprised a total of 18 European and four non-European experts, as well as two methodologists. Eight clinical questions for sCAP diagnosis and treatment were chosen to be addressed. Systematic literature searches were performed in several databases. Meta-analyses were performed for evidence synthesis, whenever possible. The quality of evidence was assessed with GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Evidence to Decision frameworks were used to decide on the direction and strength of recommendations. Recommendations issued were related to diagnosis, antibiotics, organ support, biomarkers and co-adjuvant therapy. After considering the confidence in effect estimates, the importance of outcomes studied, desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention and implications to health equity, recommendations were made for or against specific treatment interventions. In these international guidelines, ERS, ESICM, ESCMID, and ALAT provide evidence-based clinical practice recommendations for diagnosis, empirical treatment, and antibiotic therapy for sCAP, following the GRADE approach. Furthermore, current knowledge gaps have been highlighted and recommendations for future research have been made.

Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia.

The bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins. We present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival. We found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models. These findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens.