Severe Community-acquired Pneumonia Patients Research Articles

Relationship between neutrophil to lymphocytes ratio, red cell distribution width, procalcitonin, neutrophil to albumin ratio, and bun to albumin ratio with mortality of severe cap patients with septic shock

Background: Septic shock is one of severe community-acquired pneumonia (CAP) complication with high mortality. Various laboratory parameters had been associated with poor outcome including neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), procalcitonin, neutrophil to albumin ratio (NAR), and bun to albumin ratio (BAR). This study aimed to know the relationship between inflammatory markers with mortality of severe CAP patients with septic shock. Methods: This study is an observational analytic study using a cohort retrospective design conducted in Prof. I.G.N.G. Ngoerah General Hospital over a 3 years’ period (January 2020 to July 2023). The relative risk (RR) values showed relative risk of each parameter to mortality. Results: Of total 73 subjects, mortality was found in 68.5%. Male predominance was found (65.8%). Comorbid disease was reported in 69 subjects (94.5%), most found was cardiovascular disease (63%). Majority of the subjects did not have history of prior antibiotics use (86.3%). In multivariate analysis, it was found that NLR with cutoff ≥16.5 (p value 0.044; 95% CI 1.039-14.011; RR 3.816), procalcitonin ≥1.82 (p value 0.029; 95% CI 1.148-13.560; RR 3.945), and BAR ≥8.13 (p value 0.003; 95% CI 1.961-21.912; RR 7.399) are associated with mortality. There was no relationship between RDW ≥14.65 (p value 0.159; 95% CI 0.658-12.877) and NAR ≥4.5 (p value 0.436; 95% CI 0.429-7.106) with mortality in this study. Conclusions: Mortality of severe CAP patients with septic shock in this study is high. Higher NLR, procalcitonin, and BAR values have a significant relationship with mortality of severe CAP patients with septic shock.

Diagnostic predictability of serum miR-4793-3p and miR-1180-3p expression in community-acquired pneumonia.

Background: Early identification of community-acquired pneumonia (CAP) is crucial to prevent severe progression. Methods: The authors enrolled 150 hospitalized CAP patients and collected clinicopathologic features and blood indicators. Plasma miRNA profiling was conducted using microarray detection, and selected miRNAs were tested with reverse transcription quantitative PCR. Predictive models were built using least shrinkage and selection operator regression. Results: Least shrinkage and selection operator regression identified two miRNAs (miR-4793-3p and miR-1180-3p) that distinguished mild from severe CAP patients (area under the curve =0.948). The miRNA model outperformed D-dimer, platelet and procalcitonin (max area under the curve =0.729). Conclusion: Increased levels of miR-4793-3p and miR-1180-3p may indicate severe pneumonia development. Plasma miRNA profiling enables early prediction of severe CAP, aiding therapeutic decisions.

Predictive Value of Lysophosphatidylcholine for Determining the Disease Severity and Prognosis of Elderly Patients with Community-Acquired Pneumonia.

To investigate the clinical value of serum lysophosphatidylcholine (LPC) as a predictive biomarker for determining disease severity and mortality risk in hospitalized elderly patients with community-acquired pneumonia (CAP). This prospective, single-center study enrolled 208 elderly patients, including 67 patients with severe CAP (SCAP) and 141 with non-SCAP between November 1st, 2020, and November 30th, 2021 at the Qingdao Municipal Hospital, Shandong Province, China. The demographic and clinical parameters were recorded for all the included patients. Serum LPC levels were measured on day 1 and 6 after admission using ELISA. Propensity score matching (PSM) was used to balance the baseline variables between SCAP and non-SCAP patient groups. Receiver operative characteristic (ROC) curve analysis was used to compare the predictive performances of LPC and other clinical parameters in discriminating between SCAP and non-SCAP patients and determining the 30-day mortality risk of the hospitalized CAP patients. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with SCAP. Cox proportional hazard regression analysis was used to determine if serum LPC was an independent risk factor for the 30-day mortality of CAP patients. The serum LPC levels at admission were significantly higher in the non-SCAP patients than in the SCAP patients (P = 0.011). Serum LPC level <24.36 ng/mL, and PSI score were independent risk factors for the 30-day mortality in the elderly patients with CAP. The risk of 30-day mortality in the elderly CAP patients with low serum LPC levels (< 24.36ng/mL) was >5-fold higher than in the patients with high serum LPC levels (≥ 24.36ng/mL). Low serum LPC levels were associated with significantly higher disease severity and 30-day mortality in the elderly patients with CAP. Therefore, serum LPC is a promising predictive biomarker for the early identification of elderly CAP patients with poor prognosis.

Multi-omics analysis reveals overactive inflammation and dysregulated metabolism in severe community-acquired pneumonia patients

BackgroundSevere community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity.MethodsHere, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients.ResultsThere were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases.ConclusionThe plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

Clinical profile analysis and nomogram for predicting in-hospital mortality among elderly severe community-acquired pneumonia patients: a retrospective cohort study

BackgroundSevere community-acquired pneumonia is one of the most lethal forms of CAP with high mortality. For rapid and accurate decisions, we developed a mortality prediction model specifically tailored for elderly SCAP patients.MethodsThe retrospective study included 2365 elderly patients. To construct and validate the nomogram, we randomly divided the patients into training and testing cohorts in a 70% versus 30% ratio. The primary outcome was in-hospital mortality. Univariate and multivariate logistic regression analyses were used in the training cohort to identify independent risk factors. The robustness of this model was assessed using the C index, ROC and AUC. DCA was employed to evaluate the predictive accuracy of the model.ResultsSix factors were used as independent risk factors for in-hospital mortality to construct the prediction model, including age, the use of vasopressor, chronic renal disease, neutrophil, platelet, and BUN. The C index was 0.743 (95% CI 0.719–0.768) in the training cohort and 0.731 (95% CI 0.694–0.768) in the testing cohort. The ROC curves and AUC for the training cohort and testing cohort (AUC = 0.742 vs. 0.728) indicated a robust discrimination. And the calibration plots showed a consistency between the prediction model probabilities and observed probabilities. Then, the DCA demonstrated great clinical practicality.ConclusionsThe nomogram incorporated six risk factors, including age, the use of vasopressor, chronic renal disease, neutrophil, platelet and BUN, which had great predictive accuracy and robustness, while also demonstrating clinical practicality at ICU admission.

Development and validation of a predictive model for 30-day mortality in patients with severe community-acquired pneumonia in intensive care units.

Based on the high prevalence and fatality rates associated with severe community-acquired pneumonia (SCAP), this study endeavored to construct an innovative nomogram for early identification of individuals at high risk of all-cause death within a 30-day period among SCAP patients receiving intensive care units (ICU) treatment. In this single-center, retrospective study, 718 SCAP patients were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database for the development of a predictive model. A total of 97 patients eligible for inclusion were included from Chongqing General Hospital, China between January 2020 and July 2023 for external validation. Clinical data and short-term prognosis were collected. Risk factors were determined using the least absolute shrinkage and selection operator (LASSO) and multiple logistic regression analysis. The model's performance was evaluated through area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Eight risk predictors, including age, presence of malignant cancer, heart rate, mean arterial pressure, albumin, blood urea nitrogen, prothrombin time, and lactate levels were adopted in a nomogram. The nomogram exhibited high predictive accuracy, with an AUC of 0.803 (95% CI: 0.756-0.845) in the training set, 0.756 (95% CI: 0.693-0.816) in the internal validation set, 0.778 (95% CI: 0.594-0.893) in the external validation set concerning 30-day mortality. Meanwhile, the nomogram demonstrated effective calibration through well-fitted calibration curves. DCA confirmed the clinical application value of the nomogram. This simple and reliable nomogram can help physicians assess the short-term prognosis of patients with SCAP quickly and effectively, and could potentially be adopted widely in clinical settings after more external validations.

Comparison of Pneumonia-specific Scores, Sepsis Score and Generic Score in Predicting the Severity of Community-acquired Pneumonia: A Cross-sectional Study

Introduction: Pneumonia is defined as inflammation of the pulmonary parenchyma caused by an infectious agent. Community-acquired Pneumonia (CAP) is a heterogeneous disease with a significant disease burden, morbidity, and mortality. Severe Community-acquired Pneumonia (SCAP) has been proven to be associated with increased Intensive Care Unit (ICU) admission, mechanical ventilation, and mortality. Although several severity assessment tools are available, there is a lack of evidence to support one tool over another in patients with pneumonia. Aim: To compare the ability of pneumonia-specific scores {{Confusion, Urea, Respiratory rate, Blood pressure (CURB)- 65 and Expanded CURB-65)}, Sepsis score {quick Sepsisrelated Organ Failure Assessment (qSOFA)}, and Generic score {National Early Warning Score (NEWS)} in predicting SCAP patients at the time of hospital admission. Materials and Methods: This was a hospital-based crosssectional study conducted in the Department of Pulmonary Medicine, Government Hospital for Chest and Communicable Diseases, Andhra Medical College, Visakhapatnam, India, on 100 patients with clinically and radiologically diagnosed CAP over a period of six months from April 2023 to September 2023 after obtaining Institutional ethics clearance and informed consent. All four severity scores (CURB-65, eCURB-65, qSOFA, NEWS) were documented in each patient at the time of admission. Outcomes such as 30-day mortality and ICU admission were measured. Receiver Operating Characteristic (ROC) curve analysis was performed for mortality prediction and ICU admission for all four scoring systems, and statistical analysis was carried out using Statistical Packages for Social Sciences (SPSS) version 24.0. Results: Out of 100 patients, 62 (62%) were males, and the remaining 38 (38%) were females with a mean age of 56±15 years. The number of patients with co-morbidities was 48 (48%). Regarding addictive habits, smoking and alcohol played a significant role at 38% and 33%, respectively. A 30- day mortality was observed in 18 (18%) patients, and 20 (20%) patients received ICU treatment. The frequency of patients with co-morbidities such as Diabetes Mellitus (DM), Hypertension (HTN), Ischaemic Heart Disease (IHD), and Chronic Obstructive Pulmonary Disease (COPD) was 21%, 33%, 5%, and 3%, respectively. For ICU admission as an outcome measure, the Area Under Receiver Operating Characteristics (AUROC) values were as follows: CURB-65: 0.977 (95% CI: 0.949-1.00, p-value &lt;0.001); Expanded CURB-65: 0.966 (95% CI: 0.931-1.00, p-value &lt;0.001); qSOFA: 0.935 (95% CI: 0.881-0.989, p-value &lt;0.001); NEWS score: 0.967 (95% CI: 0.934-1.00, p-value &lt;0.001). Conclusion: In the present study, all four scoring systems were equally effective in detecting the need for ICU admission and predicting 30-day mortality among CAP patients at the time of admission. However, organ-specific tools (CURB-65 (2-3) moderate) have demonstrated valid and effective means of assessing severity compared to sepsis scores and generic tools.

Clinical effects of bacteremia in sepsis patients with community-acquired pneumonia

BackgroundData regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness.MethodsWe enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness.ResultDuring the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens.ConclusionThe incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia

Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

CD4+ T cells related to disease severity in elderly and frailty community-acquired pneumonia patients: A retrospective cohort study.

Elderly and frailty individuals show a more senescent immune system, which may relate to worse outcome in community-acquired pneumonia (CAP). This study aimed to explore prognostic factors related to immune. Sixty of elderly (≥65 years) and frailty (clinical frailty scale ≥5 scores) nonsevere CAP patients and 60 severe CAP (SCAP) patients were recruited at our center. Clinical and laboratory data, and several assessment scores were collected. Compared with nonsevere CAP group, the elderly and frailty SCAP patients showed higher level of BMI, PaCO2 and lactate in arterial blood-gas, CURB-65 score, ICU admission, mechanical ventilation, shock accidence, and longer hospital stay using two-tailed t test. The SCAP group also showed increased CRP, IL-6, and PCT, and decreased CD3+ T cells, CD4+ T cells, and CD8+ T cells. Logistic regression analysis showed that CD4+ T cells, IL-6 and PCT were independent prognostic factors for SCAP. The area under the receiver operating characteristic (ROC) curve for CD4+ T cells combined with PCT was 0.771 (95% CI 0.683-0.859), and the sensitivity and specificity were both 76.7%. Paired t test analysis showed that low CD4+ T cells in SCAP patients increased after treatment. CD4+ T cells decreased in elderly and frailty SCAP patients, and CD4+ T cells combined with PCT were relatively accurate in the prediction of elderly and frailty SCAP.

Clinical Evaluation of Metagenomic Next-Generation Sequencing and Identification of Risk Factors in Patients with Severe Community-Acquired Pneumonia.

Severe community-acquired pneumonia (SCAP) is the leading cause of death among patients with infectious diseases worldwide. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) through detecting pathogens in bronchoalveolar lavage fluid (BALF) and identifying risk factors for recovery in SCAP patients. This prospective study recruited 158 SCAP patients admitted to respiratory intensive care unit that were randomly divided into control and study groups, with receiving conventional tests and the same conventional tests plus mNGS, respectively. The diagnostic efficiency of mNGS was evaluated by comparing with conventional tests. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for recovery in SCAP patients, and a nomogram prediction model was established based on these factors. Within the study group, the pathogen detection rate was significantly higher with mNGS than that with conventional tests (84.81% vs 45.57%, P < 0.001), with a positive coincidence rate of 94.44%. Acinetobacter baumannii (21.52%, 17/79), Candida albicans (17.72%, 14/79), and Klebsiella pneumonia (15.19%, 12/79) were the top three common pathogens detected by mNGS. Of note, the improvement rate of patients in the study group was significantly higher than that in the control group. The further analysis revealed that the increased levels of interleukin-6, blood urea nitrogen, procalcitonin, the longer length of hospital stay, and bacterial infection were independent risk factors for recovery of SCAP patients, while mNGS detection status was a protective factor. The predictive model showed a good performance for the modeling and validation sets. Early mNGS exhibited a superior diagnostic efficiency to conventional tests in SCAP patients, which can reduce the risk of death in SCAP patients. Moreover, the clinical factors could also be used for the management and prognosis prediction of SCAP patients.

Serum Krebs von den Lungen-6 is associated with in-Hospital mortality of patients with severe Community-Acquired Pneumonia: A retrospective cohort study

BackgroundCurrently, no ideal biomarker can accurately stratify the risk of patients with severe community-acquired pneumonia (SCAP). This study aimed to evaluate the role of serum Krebs von den Lungen-6 (sKL-6) in predicting in-hospital mortality in adults with SCAP. MethodsIn this retrospective cohort study, 249 severe pneumonia adult patients were recruited between 6 May 2021 to 30 April 2023 in Xiangya Hospital of Central South University. The sKL-6 level within 48 h of admission was measured, and the primary outcome assessed was in-hospital mortality. Multivariable logistic regression analysis was performed to calculate adjusted odds ratios (OR) with 95% confidence intervals (CI). Survival curves were plotted and subgroup analyses were conducted, stratified by relevant covariates. ResultsA total of 249 patients were included in the study,with 124 patients having normal sKL-6 levels, and 125 patients having abnormal sKL-6 levels. The overall in-hospital mortality rate was 28.9% (72 out of 249 patients). Univariate and multivariate logistic regression analysis revealed that the patients with abnormal sKL-6 levels had a higher risk of in-hospital mortality compared to those with normal sKL-6 levels, both in the total SCAP patient population (OR: 5.38, 95%CI: 2.41–12.01, P < 0.001) and the non-COVID-19 SCAP patients subgroup (OR: 8.12, 95%CI: 3.16–20.84, P < 0.001). Subgroup and interaction analyses confirmed the stability of the relationship between sKL-6 levels and in-hospital mortality(P for interaction > 0.05). Kaplan-Meier survival curves showed that patients with abnormal sKL-6 levels had a higher in-hospital mortality rate than those with normal sKL-6 levels (P < 0.05). However, the results of restricted cubic spline plots(RCS) analysis demonstrated a nonlinear association between sKL-6 levels (as a continuous variable) and in-hospital mortality in patients with SCAP. Similar results were observed in non-COVID-19 SCAP patients. Furthermore, the receiver operating characteristic curve (ROC) analysis revealed that sKL-6 had superior predictive performance compared to existing biomarkers (e.g., APACHE-II, SOFA, BUN/Cr, PCT, and D-dimer) for in-hospital mortality in non-COVID-19 SCAP patients. ConclusionsKL-6 is a practical and useful biomarker for predicting in-hospital mortality in patients with SCAP.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.

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

To the Editor: Community-acquired pneumonia (CAP) in adults refers to inflammation of the lung parenchyma involving the alveolar wall. It occurs in the community environment (outside the hospital), including pneumonia caused by pathogens with definite latency after admission. CAP is still the main burden of medical and health resources. With the use of broad-spectrum antimicrobial agents, the aging population, and the emergence of new pathogens, the pathogen spectrum of CAP has changed. In addition to the traditional methods of microbiological cultivation and immunology detection, nucleic acid testing is playing more and more important roles in pathogen detection, which has greatly expanded the detection scope of pathogen. Presently, there is no epidemiological survey of the pathogenic changes in Fujian province. Thus, we carried out retrospective epidemiological studies on CAP pathogens in four centers in different regions of Fujian, and analyzed the effects of age and season on the distribution of pathogens, in order to provide a theoretical basis for regional CAP diagnosis and treatment. This study enrolled the data from 2012 to 2018 except those in 2019-2022 because coronavirus disease 2019 (COVID-19) epidemic may pose certain impact on the distribution of pathogens of CAP. This study was approved by the Ethics Committee of Fujian Provincial Hospital (No. K2019-12-032). All patients signed informed consent form. From March 2012 to December 2018, patients with CAP in four hospitals (Fujian Provincial Hospital, Wuyishan Municipal Hospital, Putian University Affiliated Hospital, and Sanming First Hospital Affiliated to Fujian Medical University) in various regions of Fujian, a total of 791 people, were included in this retrospective study. The inclusion criteria were as follows: (1) ≥18-year-old adults requiring hospitalization with an onset within 7 days; (2) respiratory symptoms, such as fever, cough, or sore throat; (3) chest radiograph or chest computed tomography (CT) showing pneumonia; (4) signing the informed consent and passing the review of the medical ethics committee of hospitals; and (5) excluding non-infectious lung diseases. Continuous airway samples were collected from the enrolled patients. The first choice for respiratory samples was bronchoalveolar lavage fluid (BALF) or tracheal secretions, and the minimum requirement was deep induced sputum. The collection process should follow sterile principles to avoid contamination of the environment and human body symbiotic bacteria or miscellaneous bacteria. The first collection time was within 48 h of admission. The samples were collected every 2 days; at least two consecutive samples were required. Qualified sputum specimens were screened by microscopy (squamous epithelial cells <10 cells/low power field [LPF], polynuclear leukocytes >25/LPF, or the ratio of the two was <1:2.5). And the respiratory samples were inoculated on blood agar, chocolate, and Chinese blue plates for bacterial culture. NucliSENS® easyMAG™ (bioMérieux ref 280140) (bioMérieux SA, Firenze, Italy) automated nucleic acid extraction equipment was used to obtain nucleic acid from respiratory tract specimens and Bio-Rad fluorescent quantitative polymerase chain reaction (PCR) instrument (model CFX96) (Bio-Rad Laboratories, Inc., Singapore) and Fast-Track Diagnostics (FTD) (Premedical Laboratories Co., Ltd., Malta) kit were used to detect the nucleic acid of pathogens in the specimens. These mainly included influenza A virus (Flu-A), human metapneumovirus (hMPV), human parainfluenza virus (hPIV), respiratory syncytial virus (RSV), adenovirus (ADV), Streptococcus pneumoniae (S. pneumoniae), Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus), Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). Criteria for positive results: (1) The same pathogen was cultured twice in a row and with bacterial colony ≥ +++; (2) There were positive and negative quality controls in the nucleic acid test. When the negative control product had no amplification curve, the positive quality control product had an amplification curve and cycle threshold <35, the test sample had a typical "S" type amplification curve and cycle threshold <35, and it was judged as positive. When the pathogen culture is inconsistent with the nucleic acid detection, the clinical manifestations and treatment response should be considered. All analyses were carried out using SPSS version 23.0 (SPSS Inc., Chicago, IL, USA). Normally distributed quantitative variables were evaluated by Student's t-test, while categorical variables were assessed by Pearson's Chi-squared test or Fisher's exact test. The bootstrap method was used to calculate the 95% confidence interval (CI). P-value <0.05 was considered statistically significant. Among 791 patients, 66.2% (524 cases) were males, and 33.8% (267 cases) were females, with an average age of 64 ± 16 years. The characteristics of patients are shown in Supplementary Table 1, https://links.lww.com/CM9/B479. In respiratory samples, BALF specimens accounted for 13.5% (107 cases), and sputum specimens accounted for 86.5% (684 cases). All respiratory samples were tested by PCR and pathogens were identified in 493/791 (62.3%) patients. Forty-seven cases were culture-positive at the same time, among which six cases were detected with pathogens inconsistent with PCR results. Combined with the clinical manifestations and treatment response of these patients, the cultured strains were considered as colonizing bacteria, and the PCR test results were in line with the clinical manifestations. The main pathogen composition is shown in Supplementary Figure 1A, https://links.lww.com/CM9/B479. And viral infection, bacterial infection, and atypical pathogen infection accounted for 32.2% (255/791), 39.2% (310/791) and 8.7% (59/791), respectively. Flu-A was the most common pathogen with a positive rate of 20.5% (162 cases), followed by S. pneumoniae 12.8% (101 cases), K. pneumoniae 8.6% (68 cases), S. aureus 6.4% (51 cases), and C. pneumoniae 5.2% (41 cases). 186 of 791 patients had mixed infections, accounting for 23.5% of cases Supplementary Figure 1B, https://links.lww.com/CM9/B479. The infection of S. aureus, C. pneumoniae, K. pneumoniae, S. pneumoniae, and RSV was mostly co-infected with other pathogens. Among patients infected with S. aureus (51 cases), 41 cases had mixed infections, accounting for 80.4%, and 73.2% (30/41) of patients infected with C. pneumoniae had mixed infections. M. pneumoniae and ADV were rarely co-infected with other pathogens [Supplementary Figure 1C, https://links.lww.com/CM9/B479]. Patients with severe community-acquired pneumonia (SCAP) accounted for 7.7% (61 cases), with a male-to-female ratio of 4.5:1. The 65- to 79-year-old age group constituted the majority of the cohort, accounting for (39.3%, 24 cases). The top four pathogens detected in SCAP were K. pneumoniae (21.3%, 13 cases), Flu-A, (19.7%, 12 cases), S. pneumoniae (16.4%, 10 cases), and S. aureus (9.8%, 6 cases) [Supplementary Figure 1D, https://links.lww.com/CM9/B479]. The epidede-mic peak of Flu-A was mostly in winter and spring. Despite a high detection rate of S. pneumoniae every year, it continued to decline from 2013 to 2017, while the detection rate of K. pneumoniae has increased year by year. The detection rate of atypical pathogens fluctuated between 7.2% and 14.3% from 2013 to 2017 [Supplementary Figure 1E, https://links.lww.com/CM9/B479]. Compared to the Fuzhou area, the detection rates of Flu-A, K. pneumoniae, S. aureus, and M. pneumoniae were higher in the non-Fuzhou area (P <0.001, = 0.001, 0.021, 0.035, respectively) [Supplementary Figure 1F, https://links.lww.com/CM9/B479].In the four age groups, Flu-A was the most common pathogen. M. pneumoniae were detected more frequently in the 18–49-year-old patients than the other three groups (7.9% [11/139] vs. 2.6% [17/652], χ2 = 9.448, P = 0.002). In addition, among patients <65 years old, the detection rate of ADV was sigificantly higher than that in patients aged ≥65 years old (3.1% [11/356] vs. 0.9% [4/435], χ2 = 4.957, P = 0.026) [Supplementary Figure 1G and Supplementary Table 2, https://links.lww.com/CM9/B479]. In our study, the results showed that the positive rate of pathogen detection was 62.8%. The viral detection rate was 32.2%, among which the Flu-A virus was the most common one. The bacterial detection rate was 39.2%, and the common bacterial pathogens were S. pneumoniae, K. pneumoniae, and S. aureus, but the detection rate of atypical pathogens was less. These findings were similar to the previous results of our study.[1] However, it was not the same as the CAP etiology survey >10 years ago in China, in which the detection rate of atypical pathogens reached nearly 1/3.[2–4] Further research found that K. pneumoniae was the most common pathogen in patients with SCAP, followed by Flu-A, S. pneumoniae, and S. aureus. K. pneumoniae ranked the first in the pathogen detection rate of SCAP in our cohort, which has not been found in previous studies, and may be due to more elderly patients than before. The status of K. pneumoniae in domestic SCAP surpassed that of S. pneumoniae, which requires sufficient clinical attention in a nowadays aging society. These results suggested the changes in the CAP pathogen spectrum over the past 10 years and could be attributed to the following reasons. Firstly, the increase in detection methods in recent years, especially nucleic acid testing assay, results in higher detection sensitivity than previous pathogen cultivation or serological detection methods. Secondly, the increase in underlying diseases due to the advent of an aging society and the widespread use of antibacterial drugs may cause changes in pathogen detection. A European study of 1166 SCAP patients admitted to the intensive care unit (ICU) showed that the common organisms were S. pneumoniae (28.6%), S. aureus (5.9%), Legionella pneumophila (L. pneumophila) (5.5%), and Haemophilus influenzae (4.8%), while the virus detection was less, accounting for only 1.4%, which was obviously different from our study.[5] Another foreign retrospective study of patients with SCAP from 1999 to 2013 found that S. pneumoniae (41.7%), L. pneumophila (6.3%), and viruses (5.4%) were the main pathogens.[6] It was also not similar to our results, suggesting that there were obvious differences in the pathogen spectrum of SCAP in China and abroad, which may be related to the different regions and the antibiotic use policy of different countries. Nevertheless, the present study had some limitations: (1) The PCR assay mainly used in this study had more potential to be false positive although it had higher detection sensitivity than the other methods. Moreover, we detected only 10 pathogens, with some common CAP pathogens not included. (2) This study lacked data on antibiotic resistance and the application of antibiotics before admission, which might cause a certain deviation in the results. (3) Since this study was only conducted in four central hospitals in Fujian Province, which might have the risk of bias. Therefore, more centers should be covered in the future to ensure the validity of the study. Funding This study was supported by grants from the National Science and Technology Major Special Project (No. 2017ZX10103004), Natural Science Foundation of Fujian Province (No. 2019J01178), and Fujian Provincial Hospital "Creating Double High" Flint Fund project (No. 2019HSJJ11). Conflicts of interest None.

Microbiological diagnostic performance of metagenomic next-generation sequencing compared with conventional culture for patients with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is an extraordinarily heterogeneous illness, both in the range of responsible pathogens and the host response. Metagenomic next-generation sequencing (mNGS) is a promising technology for pathogen detection. However, the clinical application of mNGS for pathogen detection remains challenging. A total of 205 patients with CAP admitted to the intensive care unit were recruited, and broncho alveolar lavage fluids (BALFs) from 83 patients, sputum samples from 33 cases, and blood from 89 cases were collected for pathogen detection by mNGS. At the same time, multiple samples of each patient were tested by culture. The diagnostic performance was compared between mNGS and culture for pathogen detection. The positive rate of pathogen detection by mNGS in BALF and sputum samples was 89.2% and 97.0%, which was significantly higher (P < 0.001) than that (67.4%) of blood samples. The positive rate of mNGS was significantly higher than that of culture (81.0% vs. 56.1%, P = 1.052e-07). A group of pathogens including Mycobacterium abscessus, Chlamydia psittaci, Pneumocystis jirovecii, Orientia tsutsugamushi, and all viruses were only detected by mNGS. Based on mNGS results, Escherichia coli was the most common pathogen (15/61, 24.59%) of non-severe patients with CAP, and Mycobacterium tuberculosis was the most common pathogen (21/144, 14.58%) leading to severe pneumonia. Pneumocystis jirovecii was the most common pathogen (26.09%) in severe CAP patients with an immunocompromised status, which was all detected by mNGS only. mNGS has higher overall sensitivity for pathogen detection than culture, BALF, and sputum mNGS are more sensitive than blood mNGS. mNGS is a necessary supplement of conventional microbiological tests for the pathogen detection of pulmonary infection.

Biomarkers for Lipid and Albumin Metabolism in Hospitalized Patients with Underlying Diseases and Community-Acquired Pneumonia Caused by Bacterial or SARS-CoV-2 Infection.

To look at the differences and similarities in albumin and lipid metabolism in non-severe COVID-19 infection, non-severe community-acquired pneumonia, and severe community pneumonia with underlying diseases, as well as the relationship between albumin and lipid metabolism and inflammatory mediators. This retrospective analysis comprised 253 individuals with bacterial pneumonia and COVID-19 infection (1 May 2021-1 May 2022). Routine blood examination, blood lipid levels, albumin level, C-reactive protein (CRP) levels, coagulation function, cardiac enzymes, liver function, renal function, immunological function, and bacterial culture were also collected. Correlation analysis was performed using Spearman's test for lipid parameter and Inflammatory factors in the blood. Furthermore, the multiple linear regression (MLR) analysis was employed to analyze the multicollinearity in lipidomics data. The statistical analysis was performed using SPSS statistic version 19.0. There were 63 (24.90%) non-severe community-acquired pneumonia patients (NSCAP), 48 (18.97%) severe community-acquired pneumonia patients (SCAP), 112 (44.27%) non-severe COVID-19 infection patients (NSCOV), and 30 (11.86%) healthy volunteers (HV). In all, 45.59% (116/253) of the patients had underlying diseases. Patients with community-acquired pneumonia had lower albumin and cholesterol levels than those with non-severe COVID-19 infection and healthy controls (t = -3.81, -2.09, P = 0.00, 0.04). Albumin, triglyceride, cholesterol, and LDL-C levels in peripheral blood were considerably lower in the SCAP group than in the NSCAP group. Albumin, cholesterol, HDL-C, LDL-C, and aop-A were all inversely connected with CRP in the SCAP with underlying illness group, but cholesterol level was favorably correlated with lymphocyte count (R = 0.36, P = 0.01). Hypoproteinemia, hypotriglyceridemia, and an elevated neutrophil-to-lymphocyte count ratio are all risk factors for severe community-acquired pneumonia. Hypoalbuminemia and abnormal lipid metabolism are important indicators of bacterial infection, especially severe bacterial pneumonia.

Comparison of Short-Term Versus Long-Term Antibiotic Therapy Among Severe Cases of Pneumonia: A Prospective Observational Study Among Children.

Introduction Pneumonia continues to be the leading cause of morbidity and mortality in children younger than five years. The World Health Organization (WHO)recommends intravenous antibiotics for five days for severe pneumonia. However, the optimum duration of parenteral antibiotic therapy for pneumonia is not practicable and feasible in poor and resource-constrained settings like India. Given thecurrent Indian scenario wherein childhood pneumonia is extremely prevalent, we attempted to undertake this study to compare theduration of antibiotic therapy in severe cases of community-acquired pneumonia (CAP). Methods A prospective observational study was carried out on 225 cases of severe and very severe CAP patients at a tertiary care center. The study group included children between two months to five years of age. The participants were subjected to antibiotic therapy (parenteral) plus supportive care. The selection of antibiotics was empirical and according to the WHO acute respiratory infection control program. Hematological parameters including blood hemoglobin, C-reactive protein, erythrocyte sedimentation rate (ESR), and total leukocyte count, and radiological evaluation were performed on all the participants. Cases were followed up for the duration of clinical response. Results Out of the 225 cases, 25 patients did not respond to antibiotics and were categorized as the treatment failure group. Of the remaining 200 cases, 104 (52%) showed clinical response within three days (3.0±0.016), and 96 showed a response in four to seven days (4.4±0.064). The mean duration of antibiotic therapy among short-course versus long-course treatment wasstatistically significant (p<0.0001). The majority of patients developed leukocytosis, neutrophilia, and elevated ESR. Conclusion Short-course parenteral antibiotics therapy was equally effective as long-coursetherapy in severe pneumonia. However, very severe pneumonia patients required a longer course of parenteral antibiotics therapy.Very severe pneumonia was significantly associated with high mortality and treatment failure.

A Retrospective Study on Factors Associated with Severe Childhood Community-Acquired Pneumonia

Background and Aim: Globally, community-acquired pneumonia (CAP) is the most common source of mortality among children. Early diagnosis and effective management need the identification of risk factors. The purpose of this study was to characterize the clinical symptoms and investigation of various risk factors for severe CAP in children. Patients and Methods: A retrospective study was conducted on 186 children in the Pediatric Department of Niazi Welfare Teaching Hospital, Sargodha from March 2022 to November 2022. Children with pneumonia who had radiological confirmation were included. Community-acquired pneumonia cases were categorized into two groups: Group-I composed of severe CAP cases whereas Group-II non-severe CAP cases. Baseline characteristics such as age, nutritional status, and gender were collected. Vital signs, fever, duration of symptoms, and physical findings such as chest retraction, cyanosis, wheezing, and nasal faring were clinical data recorded. Laboratory findings such as serum electrolyte, full blood count, and inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded. SPSS version 27 was used for data analysis. Results: Of the total 186 children, there were 74 (39.8%) females and 112 (60.2%) male. Age-wise distribution of patients were as follows: 146 (78.5%) in 0-5 years, 26 (14%) in 6-10 years, and 14 (7.5%) in 11-15 years. Out of 186 children, the incidence of severe and non-severe CAP was 58 (31.2%) and 130 (68.8%) respectively. The most common clinical signs in both categories are fever and cough, followed by reduced appetite, vomiting, and shortness of breath. A seizure is present in 14 (24.1%) severe CAP cases. Based on physical examination, Rhonchi is found in 94 (72.3%) non-severe and 46 (79.3%) severe CAP patients. Among patients with severe pneumonia, over half have chest retractions, but only 22% have non-severe pneumonia. Tachypnea was experienced by approximately 33% of severe pneumonia patients against 14% of individuals with non-severe pneumonia. As inflammatory indicators, ESR and CRP are high in all groups. Conclusion: The present study concluded that a fever persisting for &gt;7 days and an elevation in RR are risk factors for severe pneumonia. Severe pneumonia is also prevented by a normal hematocrit level and BMI. There was a higher rate of severe pneumonia in CAP hospitalizations in children who had fevers lasting longer than seven days as well as tachypnea. According to these findings, RR should be utilized to determine both the severity of pneumonia and the identification of pneumonia. Keywords: Sever community-acquired pneumonia, Risk factors, Childhood pneumonia

Outcomes and Predictors of Severe Community-acquired Pneumonia Among Adults Admitted to the University of Gondar Comprehensive Specialized Hospital: A Prospective Follow-up Study.

Severe community-acquired pneumonia is a common life-threatening infection with a high rate of unfavorable outcome. This study aimed to assess the outcomes and predictors of hospitalized severe community-acquired pneumonia patients at University of Gondar comprehensive specialized hospital. A prospective follow-up study was conducted at University of Gondar comprehensive specialized hospital from May 1 to September 31, 2021. The data was collected by reviewing patients' charts and interviewing the patients themselves. Descriptive statistics, binary and multivariable logistic regression analysis were performed accordingly. Variables with p-value <0.2 on binary logistic regression were analyzed using multivariable logistic regression and variables with p<0.05 were considered to have significant association. A total of 239 admitted patients with severe community-acquired pneumonia were enrolled in the study. An unfavorable outcome was observed in 105 (44%) patients; 24.27% was in-hospital all-cause mortality, 12.5% was nonresolution, 5.8% was complicated cases, and 1.26% were gone against medical care for poor prognosis. After analyzing multivariable logistic regression, confusion (OR= 4.84; 95%CI: 1.47-15.88), anemia (OR= 2.36; 95%CI: 1.01-5.52), leukopenia (OR=4.38; 95%CI: 1.26-15.25), leukocytosis (OR=3.15; 95%CI: 1.23-7.96), elevated creatinine (OR=5.67; 95%CI: 1.72-18.65), intubation (OR=7.27; 95%CI: 1.58-33.37) and antibiotic revision during treatment for a different reason (OR=0.02; 95%CI: 0.01-0.07) were variables significantly associated with unfavorable outcome. Unfavorable outcome was high among hospitalized severe community acquired pneumonia patients, and confusion, elevated creatinine, anemia, leukopenia, leukocytosis, intubation during admission, and antibiotic revision during the course were independent predictors associated significantly with the unfavorable outcome. It is important to consider the development of a treatment protocol for the hospital and to further research incorporating the microbiologic profile of the patients.

Derivation and external validation of a prediction model for pneumococcal urinary antigen test positivity in patients with community-acquired pneumonia.

Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity. Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity. Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27-11.46), severe CAP on admission (OR 1.76, 95% CI 1.56-1.98), substance abuse (OR 1.57, 95% CI 1.27-1.93), smoking (OR 1.23, 95% CI 1.09-1.39), and hyponatremia (OR 1.35, 95% CI 1.17-1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52-0.82), congestive heart failure (OR 0.72, 95% CI 0.63-0.83), obesity (OR 0.71, 95% CI 0.60-0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45-0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests. Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship.