Severe Community-acquired Pneumonia Research Articles

Pneumococcal Neuraminidases Increase Platelet Killing by Pneumolysin.

Platelets prevent extravasation of capillary fluids into the pulmonary interstitial tissue by sealing gaps in inflamed endothelium. This reduces respiratory distress associated with pneumonia. Streptococcus pneumoniae is the leading cause of severe community-acquired pneumonia. Pneumococci produce pneumolysin (PLY), which forms pores in membranes of eukaryotic cells including platelets. Additionally, pneumococci express neuraminidases, which cleave sialic acid residues from eukaryotic glycoproteins. In this study, we investigated the effect of desialylation on PLY binding and pore formation on platelets. We incubated human platelets with purified neuraminidases and PLY, or nonencapsulated S. pneumoniae D39/TIGR4 and isogenic mutants deficient in PLY and/or NanA. We assessed platelet desialylation, PLY binding, and pore formation by flow cytometry. We also analyzed the inhibitory potential of therapeutic immunoglobulin G preparations (IVIG [intravenous immunoglobulin]). Wild-type pneumococci cause desialylation of platelet glycoproteins by neuraminidases, which is reduced by 90 to 100% in NanA-deficient mutants. NanC, cleaving only α2,3-linked sialic acid, induced platelet desialylation. PLY binding to platelets then x2doubled (p = 0.0166) and pore formation tripled (p = 0.0373). A neuraminidase cleaving α2,3-, α2,6-, and α2,8-linked sialic acid like NanA was even more efficient. Addition of polyvalent IVIG (5 mg/mL) decreased platelet desialylation induced by NanC up to 90% (p = 0.263) and reduced pore formation >95% (p < 0.0001) when incubated with pneumococci. Neuraminidases are key virulence factors of pneumococci and desialylate platelet glycoproteins, thereby unmasking PLY-binding sites. This enhances binding of PLY and pore formation showing that pneumococcal neuraminidases and PLY act in concert to kill platelets. However, human polyvalent immunoglobulin G preparations are promising agents for therapeutic intervention during severe pneumococcal pneumonia.

Distribution characteristics of human herpes viruses in the lower respiratory tract and their impact on 30-day mortality in community-acquired pneumonia patients.

Human herpes viruses (HHVs) are commonly detected in community-acquired pneumonia (CAP) patients, particularly those with complex complications, attracting increased attention from clinical practitioners. However, the significance of detecting HHVs in bronchoalveolar lavage fluid (BALF) with CAP patients is still unclear. This study retrospectively analyzed BALF samples from 64 CAP patients at the Kunming Third People's Hospital between August 2021 and December 2023. Metagenomic next generation sequencing (mNGS) was conducted on BALF samples during CAP onset. Multivariate Cox regression models were used to identify independent risk factors for 30-day all-cause mortality in CAP. HHVs were found in 84.4% of CAP patients, which were the most common pathogens (45.1%), followed by bacteria (30.2%) and fungi (11.5%). Bacterial-viral co-infections were most common, occurring in 39 patients. Notably, there was no significant difference in HHV presence between severe and non-severe CAP patients (EBV: P = 0.431, CMV: P = 0.825), except for HHV-7 (P = 0.025). In addition, there was no significant difference in the 30-day mortality between HHV positive and HHV negative groups (P = 0.470), as well as between the HHV-7 positive and HHV-7 negative groups (P = 0.910). However, neither HHVs nor HHV-7 was independent risk factors for 30-day mortality in CAP patients (HHVs: HR 1.171, P = 0.888; HHV-7: HR 1.947, P = 0.382). In summary, among the prevalent presence of multiple HHVs, EBV and CMV were the most prevalent in CAP patients. Patients with sCAP were more susceptible to HHV-7 than those with non-sCAP. These results provide valuable insights for clinicians in guiding appropriate interventions for CAP treatment.

Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID)

BackgroundTrimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death.MethodsAdults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29).ResultsOne-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable.A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 109/L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: −4.46, 34.78; P = 0.096).ConclusionAlthough there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation.ESsCOVID was registered prospectively at ClinicalTrials.gov on October 6, 2020.NCT04576728

Mapping Host-Microbe Omics Interactions in Severe Community-acquired Pneumonia

Mapping Host-Microbe Omics Interactions in Severe Community-acquired Pneumonia

Low thoracic skeletal muscle is a risk factor for 6-month mortality of severe community-acquired pneumonia in older men in intensive care unit

BackgroundPatients with severe community-acquired pneumonia (sCAP) admitted to the intensive care unit (ICU) often exhibit muscle catabolism, muscle weakness, and/or atrophy, all related to an increased morbidity and mortality. However, the relationship between thoracic skeletal muscle mass and sCAP-related mortality has not been well-studied. Early recognition of sarcopenia in ICU patients with sCAP would benefit their prognosis.MethodsA retrospective study was conducted in Taizhou Hospital of Zhejiang Province, involving 101 patients with sCAP admitted in the ICU between December 2022 and February 2023. We measured the cross-sectional aera of the pectoralis, intercostal, paraspinal, serratus, and latissimus muscles at the T4 vertebral level (T4CSA) using chest computed tomography. Discriminatory thresholds were established by performing receiver operating characteristic curve analysis, with a designated cutoff value of 96.75 cm2 for male patients. This cohort was classified into mortality and survival groups based on a 6-month post-admission outcome. Univariate and multifactorial logistic regression analyses were performed to validate the correlation between low thoracic skeletal muscle area and prognostic outcomes.ResultsThe mean age of the patients was 75.39 ± 12.09 years, with an overall 6-month mortality of 73.27%. T4CSA of the 6-month survival group was significantly larger than that in the mortality group for overall cohort. The T4CSA in the survival group was significantly larger than that in the mortality group (104.29 ± 23.98cm2 vs. 87.44 ± 23.0cm2, p = 0.008). T4CSA predicted the 6-month mortality from sCAP in males with an AUC of 0.722 (95% confidence interval (CI), 0.582–0.861). The specificity and sensitivity were 71.4% and 71.1%, respectively, (p < 0.05). No significant difference was observed between the two groups in terms of T4CSA.ConclusionsThis study revealed that low thoracic skeletal muscle mass increased the risk of all-cause 6-month mortality in ICU patients with sCAP, particularly among male patients.

Time to recovery from severe community-acquired pneumonia and its predictors among 6 to 59 months of age children admitted to South Wollo zone public hospitals, North East Ethiopia: a prospective follow-up study

IntroductionEthiopia is one of those countries with higher burden of community acquired pneumonia among its people, under five children are the members of society that are highly affected by pneumonia particularly Severe Community Acquired Pneumonia. However, there are limited studies on time to recovery and its predictors in under-five children and most of them are retrospective which fails to address important variables that affect the time to recovery. Therefore, the aim of this study was to estimate the median time to recovery and its predictors among under five children admitted to South Wollo zone public hospitals, North East Ethiopia.MethodsAn institution-based prospective cohort study was conducted from March 10 to May 10, 2021, with 270 study subjects. A systematic random sampling technique was used. Data was collected by interview and chart review. The data were entered and analyzed using Epi Data version 3.1 and STATA version 14.0, respectively. Kaplan-Meier and Cox regression models were used to test the time and predictors of recovery from severe community-acquired pneumonia.ResultsThe overall incidence of recovery rate (95% confidence interval) from Severe Community-Acquired Pneumonia was 20.45(17.84–23.46) per 100 person days observation with median (IQR) time to recovery of [3, 5] days. The predictors of time to recovery from Severe Community-Acquired Pneumonia were having comorbidities on admission [AHR = 0.49 (95%CI: 0.32,0.75)], reaching hospitals after 5 days of onset of symptoms [AHR = 0.35 (95%CI: 0.20,0.60)], having Middle Upper Arm Circumference < = 12.5 cm [AHR = 0.21 (95%CI: 0.12,0.37)], the presence of smoker in the house [AHR = 0.21 (95%CI: 0.10,0.42)] and being not fully immunized for age [AHR = 0.35 (95%CI: 0.24,0.53)].Conclusion and recommendationsGenerally the recovery time of children with Severe Community Acquired Pneumonia in the study area was within the recommended national standards. Due attention should be given to children with the identified predictors while treating them.

A radiomics model utilizing CT for the early detection and diagnosis of severe community-acquired pneumonia

BackgroundCommunity-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes.MethodsA retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35).ResultsThe radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set.ConclusionsThe radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.

Integrative Analyses Reveal the Correlation Between the Airway Microbiome and Host Metabolism in Severe Community-acquired Pneumonia.

Community-acquired pneumonia (CAP) is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe CAP remains unclear. To address this knowledge gap, we conducted a comprehensive analysis utilizing 16S sequencing and LC-MS/MS metabolomics data to characterize the microbial profile in sputum and metabolic profile in serum in patients with severe community-acquired pneumonia (sCAP). Our analysis identified 13 genera through LEfSe analysis and 15 metabolites meeting specific criteria (P < 0.05, VIP ≥ 2, and |Log2(FC)| ≥ 2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in sCAP patients have important implications for optimizing early diagnosis and developing individualized therapeutic strategies.

P31 An observational prospective audit on the use of vancomycin and ciprofloxacin in the treatment of severe community-acquired pneumonia in penicillin-allergic patients in NHS Lothian

P31 An observational prospective audit on the use of vancomycin and ciprofloxacin in the treatment of severe community-acquired pneumonia in penicillin-allergic patients in NHS Lothian

Clinical progress note: Steroids in severe community-acquired pneumonia.

Clinical progress note: Steroids in severe community-acquired pneumonia.

MALAT1 predicts the prognosis of severe community-acquired pneumonia in pediatric patients

BackgroundTo evaluate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the prognosis of severe community-acquired pneumonia (CAP) in children.MethodsAccording to the median MALAT1 value of 3.2 at baseline, 93 pediatric patients with severe CAP were divided into low (n = 46, median MALAT1 level = 1.9) or high (n = 47, median MALAT1 level = 4.5) MALAT1 groups. Another 93 age-, gender-, and body mass index (BMI)-matched healthy individuals were included in the control group using the propensity-score matching (PSM) method. A multivariate Cox proportional hazards model was used to explore the association of MALAT1 level with the 28-day mortality after controlling for potential confounding factors.ResultsThe MALAT1 expressions were significantly higher in the patients with severe CAP compared with those in the healthy controls (3.2 vs. 0.9, P < 0.01). The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.927 when the cut-off value of MALAT1 was 1.5. Moreover, the MALAT1 expressions were substantially lower in survivals than non-survivals (3.8 vs. 2.6, P < 0.01), and the multivariate Cox regression analysis indicated a positive association between MALAT1 levels and mortality risk (HR = 3.32; 95% CI: 1.05–10.47; P = 0.04).ConclusionMALAT1 might be a promising marker for predicting the prognosis of severe CAP in pediatric patients.

Machine learning-based derivation and validation of three immune phenotypes for risk stratification and prognosis in community-acquired pneumonia: a retrospective cohort study.

The clinical presentation of Community-acquired pneumonia (CAP) in hospitalized patients exhibits heterogeneity. Inflammation and immune responses play significant roles in CAP development. However, research on immunophenotypes in CAP patients is limited, with few machine learning (ML) models analyzing immune indicators. A retrospective cohort study was conducted at Xinhua Hospital, affiliated with Shanghai Jiaotong University. Patients meeting predefined criteria were included and unsupervised clustering was used to identify phenotypes. Patients with distinct phenotypes were also compared in different outcomes. By machine learning methods, we comprehensively assess the disease severity of CAP patients. A total of 1156 CAP patients were included in this research. In the training cohort (n=809), we identified three immune phenotypes among patients: Phenotype A (42.0%), Phenotype B (40.2%), and Phenotype C (17.8%), with Phenotype C corresponding to more severe disease. Similar results can be observed in the validation cohort. The optimal prognostic model, SuperPC, achieved the highest average C-index of 0.859. For predicting CAP severity, the random forest model was highly accurate, with C-index of 0.998 and 0.794 in training and validation cohorts, respectively. CAP patients can be categorized into three distinct immune phenotypes, each with prognostic relevance. Machine learning exhibits potential in predicting mortality and disease severity in CAP patients by leveraging clinical immunological data. Further external validation studies are crucial to confirm applicability.

Frequency and clinical significance of Herpes simplex virus type 1/2 reactivation in adult patients with mild to moderately severe community-acquired pneumonia: a multicentre cohort study.

This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP). The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death). Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS. Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course.

Respiratory syncytial virus-associated pneumonia in primary care in Malawi.

To identify the prevalence of respiratory syncytial virus (RSV) in a cohort of children under 5 years of age with World Health Organization (WHO)-defined pneumonia and the factors associated with developing severe RSV-associated community-acquired pneumonia (CAP) in primary care in a single centre in Northern Malawi. The BIOmarkers TO diagnose PnEumonia (BIOTOPE) study was a prospective cohort study conducted from March to June 2016 that took place in a primary care centre in Northern Malawi. Data from this study was used to identify the characteristics of children under 5 years of age who presented with RSV and WHO-defined CAP. Means, standard deviations, medians and ranges were calculated for continuous variables. A univariate logistic regression was performed to examine the potential predictor variables. Four hundred and ninety-four infants presented with CAP and were eligible for inclusion in the study; RSV infection was detected in 205 (41.6%) of the infants. Eight factors were associated with increased risk for RSV CAP in the univariate model: age, born at term, presenting for care in June, crowded living environment, not being exclusively breastfed, not having received zinc or vitamin A supplementation in the last six months. Infants with RSV were more likely to have an oxygen saturation ≤92% compared to infants with other causes of pneumonia and more likely to have severe pneumonia as defined by the WHO. This study supports that RSV-associated CAP is linked to modifiable and non-modifiable risk factors; further research is indicated to determine which interventions would be most impactful. Developing and implementing an infant or maternal vaccine could be a cost-effective way to prevent RSV-associated CAP and mortality in developing nations. More research is needed to understand seasonal patterns of CAP and research over extended periods can offer valuable insights on host, environmental and pathogen-specific factors that contribute to RSV-associated CAP.

Epidemiological and clinical characteristics of respiratory syncytial virus infection among people aged 60 and above in Beijing City

Objective: To investigate the epidemiological and clinical characteristics of RSV among patients aged ≥60 years in Beijing from 2015 to 2023. Methods: Based on the respiratory pathogen surveillance system, samples of upper respiratory tract infections (URTI), non-severe community-acquired pneumonia (nsCAP) and severe community-acquired pneumonia (sCAP) among people aged ≥60 years were collected from 28 sentinel hospitals in 16 districts of Beijing from January 2015 to December 2023. Swab samples were collected from URTI within one week, and lower respiratory tract samples from nsCAP and sCAP were collected. Demographic and epidemiological data were also collected. Various respiratory pathogens including RSV were detected. Results: From January 2015 to December 2023, a total of 20 349 cases of acute respiratory infections aged ≥60 years were included, with the RSV-positive rate of 1.54% (313/20 349, 95%CI: 1.39%-1.68%). Among them, the total RSV-positive rates of older people during the pre-pandemic, pandemic, and post-pandemic periods of COVID-19 were 1.59% (207/13 006, 95%CI: 1.38%-1.81%), 0.82% (38/4 650, 95%CI: 0.56%-1.08%) and 2.53% (68/2 693, 95%CI: 1.93%-3.12%), respectively. The difference in RSV-positive rate was statistically significant (P<0.001). Based on the sampling time of cases, the RSV epidemic season for older people in Beijing was from October to March of the following year, with a peak period in December or January of the following year. In the post COVID-19 pandemic, there were very few RSV-positive cases detected in the elderly from April to June 2023, with only one positive case detected in May and one in June. The RSV-positive rate of older people increased significantly from October to December, reaching 11.75% (51/383) in December. Among 263 RSV-positive cases in the elderly, RSV-A, RSV-B and unclassified type accounted for 43.35% (114/263), 29.28% (77/263) and 27.38% (72/263), respectively. Since 2020, there has been a subtype conversion, with RSV-B being the main focus. Among 197 elderly cases that have complete clinical data, the main symptoms were cough (86.8%, 171/197), sputum (80.2%, 158/197) and fever (73.60%, 145/197). About 24.87% (49/197) of elderly cases experienced complications. The hospitalization mortality rate was 4.57% (9/197), and the hospitalization rate was 78.68% (155/197). The ICU occupancy rate was 1.99% (36/197). The mechanical ventilation usage rate was 13.32% (33/197), and the length of hospital stay [M (Q1, Q3)] was 12 (9, 16) days. Conclusion: In Beijing, the RSV infection rate is relatively low during the COVID-19 pandemic, and the prevalence of COVID-19 is relatively high. In 2023, there was no out-of-season outbreak of RSV infection among the elderly. Elderly RSV infection cases have multiple complications, severe diseases, and poor prognosis.

Association of serum interleukin-2 with severity and prognosis in hospitalized patients with community-acquired pneumonia: a prospective cohort study

The prior studies have shown that interleukin-2 (IL-2) exerts important roles in the pathological and physiological processes of lung diseases. However, the role of IL-2 in community-acquired pneumonia (CAP) is still uncertain. Through a prospective cohort study, our research will explore the correlations between serum IL-2 levels and the severity and prognosis in CAP patients. There were 267 CAP patients included. Blood samples were obtained. Serum IL-2 were tested by enzyme-linked immunosorbent assay (ELISA). Demographic traits and clinical characteristics were extracted. Serum IL-2 were gradually elevated with increasing severity scores in CAP patients. Correlation analyses revealed that serum IL-2 were connected with physiological parameters including liver and renal function in CAP patients. According to a logistic regression analysis, serum IL-2 were positively correlated with CAP severity scores. We also tracked the prognostic outcomes of CAP patients. The increased risks of adversely prognostic outcomes, including mechanical ventilation, vasoactive agent usage, ICU admission, death, and longer hospital length, were associated with higher levels of IL-2 at admission. Serum IL-2 at admission were positively associated with severe conditions and poor prognosis among CAP patients, indicated that IL-2 may involve in the initiation and development of CAP. As a result, serum IL-2 may be an available biomarker to guide clinicians in assessing the severity and determining the prognosis of CAP.

Case Report: Severe Community-Acquired Pneumonia in Réunion Island due to Acinetobacter baumannii.

Acinetobacter baumannii (Ab) is a well-known nosocomial pathogen that has emerged as a cause of community-acquired pneumonia (CAP) in tropical regions. Few global epidemiological studies of CAP-Ab have been published to date, and no data are available on this disease in France. We conducted a retrospective chart review of severe cases of CAP-Ab admitted to intensive care units in Réunion University Hospital between October 2014 and October 2022. Eight severe CAP-Ab cases were reviewed. Median patient age was 56.5 years. Sex ratio (male-to-female) was 3:1. Six cases (75.0%) occurred during the rainy season. Chronic alcohol use and smoking were found in 75.0% and 87.5% of cases, respectively. All patients presented in septic shock and with severe acute respiratory distress syndrome. Seven patients (87.5%) presented in cardiogenic shock, and renal replacement therapy was required for six patients (75.0%). Five cases (62.5%) presented with bacteremic pneumonia. The mortality rate was 62.5%. The median time from hospital admission to death was 3 days. All patients received inappropriate initial antibiotic therapy. Acinetobacter baumannii isolates were all susceptible to ceftazidime, cefepime, piperacillin-tazobactam, ciprofloxacin, gentamicin, and imipenem. Six isolates (75%) were also susceptible to ticarcillin, piperacillin, and cotrimoxazole. Severe CAP-Ab has a fulminant course and high mortality. A typical case is a middle-aged man with smoking and chronic alcohol use living in a tropical region and developing severe CAP during the rainy season. This clinical presentation should prompt administration of antibiotic therapy targeting Ab.

Effect of Metagenomic Next-Generation Sequencing on Clinical Outcomes of Patients With Severe Community-Acquired Pneumonia in the ICU: A Multicenter, Randomized Controlled Trial

Metagenomic next-generation sequencing (mNGS) was previously established as a method that can increase the pathogen identification rate in patients with severe community-acquired pneumonia (SCAP). What is the impact on clinical outcomes of mNGS of BAL fluid (BALF) in patients with SCAP in the ICU? A multicenter, randomized controlled, open-label clinical trial was conducted in 10 ICUs. Patients were randomized in a 1:1 ratio to undergo BALF assessment with conventional microbiological tests (CMTs) only (ie, the CMT group) or BALF assessment with both mNGS and CMTs (ie, the mNGS group). The primary outcome was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a six-category ordinal scale or discharge from the ICU, whichever occurred first. A total of 349 patients were randomized to treatment between January 1, 2021, and November 18, 2022; 170 were assigned to the CMT group and 179 to the mNGS group. In the intention-to-treat analysis, the time to clinical improvement was better in the mNGS group than in the CMT group (10days vs13days; difference, -2.0days; 95%CI, -3.0 to 0.0days). Similar results were obtained in the per-protocol analysis. The proportion of patients with clinical improvement within 14days was significantly higher in the mNGS group (62.0%) than in the CMT group (46.5%). There was no significant difference in other secondary outcomes. Compared with the use of CMTs alone, mNGS combined with CMTs reduced the time to clinical improvement for patients with SCAP. ChiCTR2000037894.

Development and Validation of a Risk Mortality Prediction Model for Patients with Pulmonary Tuberculosis Complicated by Severe Community-Acquired Pneumonia in the Intensive Care Unit.

The mortality rate from pulmonary tuberculosis (PTB) complicated by severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) remains high. We aimed to develop a rapid and simple model for the early assessment and stratification of prognosis in these patients. All adult patients with PTB complicated by SCAP admitted to the ICU of a tertiary hospital in Chengdu, Sichuan, China between 2019 and 2021 (development cohort) and 2022 (validation cohort) were retrospectively included. Data on demographics, comorbidities, laboratory values, and interventions were collected. The outcome was the 28-day mortality. Stepwise backward multivariate Cox analysis was used to develop a mortality risk prediction score model. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the model's predictive efficiency. Decision curve analysis (DCA) was used to validate the model's clinical value and impact on decision making. Overall, 357 and 168 patients were included in the development and validation cohorts, respectively. The Pulmonary Tuberculosis Severity Index (PTSI) score included long-term use of glucocorticoid, body mass index (BMI) <18.5 kg/m2, diabetes, blood urea nitrogen (BUN) ≥7.14 mmol/L, PO2/FiO2 <150 mmHg, and vasopressor use. The area under the ROC curve (AUC) values were 0.817 (95% CI: 0.772-0.863) and 0.814 for the development and validation cohorts, respectively. The PTSI score had a higher AUC than the APACHE II, SOFA, and CURB-65 score. The calibration curves indicated good calibration in both cohorts. The DCA of the PTSI score indicated the high clinical application of the model compared with the APACHE II and SOFA scores. This prognostic tool was designed to rapidly evaluate the 28-day mortality risk in individuals with PTB complicated by SCAP. It can stratify this patient group into relevant risk categories, guide targeted interventions, and enhance clinical decision making, thereby optimizing patient care and improving outcomes.

Comparison of Real-time Polymerase Chain Reaction and Culture for Targeting Pathogens in Pediatric Severe Community-Acquired Pneumonia.

This study aims to determine the frequency of pathogen detection by real-time polymerase chain reaction (PCR), the frequency of pathogen isolation by culture; and compare the value of real-time PCR and culture of nasopharyngeal aspiration samples in patients with severe community-acquired pneumonia (sCAP). It was a prospective and descriptive study. All pediatric patients diagnosed with sCAP were performed real-time PCR and culture of nasopharyngeal aspiration samples. A total of 336 patient samples were obtained from children with sCAP. Real-time PCR detected pathogens in 312 patients (92.9%), while culture isolated bacteria in 228 patients (67.9%). Coinfections were reported in 279 cases (83.0%) through real-time PCR. The frequency of agreement between culture and real-time PCR was quite high (P < .001). Real-time PCR demonstrated more ability for detecting microorganisms than culture. This finding highlighted the value of real-time PCR for targeting pathogens in children with sCAP, particularly in cases involving complex pathogens or those requiring timely identification.