BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP.
METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy.
RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy.
CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.

BACKGROUND: Necrotizing fasciitis (NF) is a rare but potentially life-threatening soft tissue infection. The objective of this study was to assess the association between timely surgery within 6 h and hospital mortality in patients with limb NF, and to describe the trends in patients with NF, time to surgery and standardized mortality ratio (SMR) over 11 years.
METHODS: This was a multicenter, retrospective cohort study of all intensive care unit patients who had emergency surgery within 24 h of hospitalization for limb NF between April 1, 2008 and March 31, 2019 in Hong Kong. Timely surgery was defined as the first surgical treatment within 6 h of initial hospitalization. Appropriate antibiotics were achieved if the patient was given antibiotic(s) for all documented pathogens prior to or on day of culture results. The primary outcome was hospital mortality.
RESULTS: There were 495 patients (median age 62 years, 349 (70.5%) males) with limb NF treated by surgery within 24 h of hospitalization over the 11 years. Appropriate antibiotic(s) were used in 392 (79.2%) patients. There were 181 (36.5%) deaths. Timely surgery was not associated with hospital mortality (Relative Risk 0.89, 95% CI: 0.73 to 1.07) but admission year, advanced age, higher severity of illness, comorbidities, renal replacement therapy, vasopressor use, and type of surgery were significant predictors in the multivariable model. There was an upward trend in NF diagnosis (1.9 cases/year, 95% CI: 0.7 to 3.1; P < 0.01; R2 = 0.60) but there was no downward trend in median time to surgery (-0.2 h/year, 95% CI: -0.4 to 0.1; P = 0.16) or SMR (-0.02/year, 95% CI: -0.06 to 0.01; P = 0.22; R2 = 0.16).
CONCLUSIONS: Among patients operated within 24 h, very early surgery within 6-12 h was not associated with survival. Increasing limb NF cases were reported each year but mortality remained high despite a high rate of appropriate antibiotic use and timely surgical intervention.

BACKGROUND: There is no individualized prediction model for intensive care unit (ICU) admission on patients with community-acquired pneumonia (CAP) and connective tissue disease (CTD) so far. In this study, we aimed to establish a machine learning-based model for predicting the need for ICU admission among those patients.
METHODS: This was a retrospective study on patients admitted into a University Hospital in China between November 2008 and November 2021. Patients were included if they were diagnosed with CAP and CTD during admission and hospitalization. Data related to demographics, CTD types, comorbidities, vital signs and laboratory results during the first 24 h of hospitalization were collected. The baseline variables were screened to identify potential predictors via three methods, including univariate analysis, least absolute shrinkage and selection operator (Lasso) regression and Boruta algorithm. Nine supervised machine learning algorithms were used to build prediction models. We evaluated the performances of differentiation, calibration, and clinical utility of all models to determine the optimal model. The Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) techniques were performed to interpret the optimal model.
RESULTS: The included patients were randomly divided into the training set (1070 patients) and the testing set (459 patients) at a ratio of 70:30. The intersection results of three feature selection approaches yielded 16 predictors. The eXtreme gradient boosting (XGBoost) model achieved the highest area under the receiver operating characteristic curve (AUC) (0.941) and accuracy (0.913) among various models. The calibration curve and decision curve analysis (DCA) both suggested that the XGBoost model outperformed other models. The SHAP summary plots illustrated the top 6 features with the greatest importance, including higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), lower level of CD4 + T cell, lymphocyte and serum sodium, and positive serum (1,3)-β-D-glucan test (G test).
CONCLUSIONS: We successfully developed, evaluated and explained a machine learning-based model for predicting ICU admission in patients with CAP and CTD. The XGBoost model could be clinical referenced after external validation and improvement.

BACKGROUND: Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD. However, deep investigation into microbiome distribution of lower respiratory tract of CAP with or without COPD was unknown.
METHODS: So we used metagenomic next generation sequencing (mNGS) to explore the microbiome differences between the two groups.
RESULTS: Thirty-six CAP without COPD and 11 CAP with COPD cases were retrieved. Bronchoalveolar lavage fluid (BALF) was collected and analyzed using untargeted mNGS and bioinformatic analysis. mNGS revealed that CAP with COPD group was abundant with Streptococcus, Prevotella, Bordetella at genus level and Cutibacterium acnes, Rothia mucilaginosa, Bordetella genomosp. 6 at species level. While CAP without COPD group was abundant with Ralstonia, Prevotella, Streptococcus at genus level and Ralstonia pickettii, Rothia mucilaginosa, Prevotella melaninogenica at species level. Meanwhile, both alpha and beta microbiome diversity was similar between groups. Linear discriminant analysis found that pa-raburkholderia, corynebacterium tuberculostearicum and staphylococcus hominis were more enriched in CAP without COPD group while the abundance of streptococcus intermedius, streptococcus constellatus, streptococcus milleri, fusarium was higher in CAP with COPD group.
CONCLUSIONS: These findings revealed that concomitant COPD have an mild impact on lower airway microbiome of CAP patients.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (CA-MRSA), which has the potential to produce serious infections, was a common cause of skin and soft tissue infections, acute purulent lymphadenitis was rare.
METHODS: The patient was a female infant with lumps, tenderness, and fever on the right side of the neck and groin. Laboratory tests suggested a bacterial infection. The diagnosis of acute purulent lymphadenitis was made based on the clinical signs and the results of a supporting exam. After three days, MRSA developed in the secretions of suppurative lymph nodes. Her mother\'s nasopharyngeal swab sample results revealed MRSA. The genotypes of two bacterial strains that underwent molecular analysis were identical.
RESULTS: 17 days after admission, the patient showed signs of clinical recovery.
CONCLUSIONS: The incident brought to light the possible spread of CA-MRSA in the Chinese population. Even without a definite path of infection, CA-MRSA should be taken into consideration when the standard treatment for children with acute purulent lymphadenitis is ineffective. Early infancy MRSA acquisition may be mostly caused by maternal-infant horizontal transmission.

BACKGROUND: The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia.
METHODS: This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed.
RESULTS: A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P < 0.05). The Barthel Index used to assess the activities of daily living was an independent risk factor for the severity and mortality of COVID-19 and linearly correlated with the LOS (P < 0.05). The cluster analysis based on the CGA indicators divided the geriatric pneumonia patients into three groups: Cluster 1 (n = 276), named low ability group, with the worst CGA, laboratory tests, severity, mortality, and LOS; Cluster 3 (n = 228), called high ability group with the best above indicators; Cluster 2 (n = 288), named medium ability group, falls between the two.
CONCLUSIONS: The Barthel Index indicates that decreased activities of daily living are an independent risk factor for the severity, mortality, and LOS of geriatric COVID-19. Geriatric syndrome can help judge the prognosis of pneumonia in older adults.

Over the past two to three decades, the emergence and re-emergence of new infectious diseases, advances in molecular detection techniques of pathogens, antibiotic resistance, changes in population lifestyle and immune status (including vaccination), and other factors have led to new evolutions in the etiology of community-acquired pneumonia (CAP). (1) Although Streptococcus pneumoniae remains a common pathogen of CAP, it is no longer the leading cause in China and the United States. According to the results of 2 multicenter studies in China in the early 21st century, Streptococcus pneumoniae accounted for 10.3% and 12.0% of adult CAP pathogens, respectively, ranking second. A study on key pathogens of adult CAP in nine cities in mainland China from 2014 to 2019 using real-time quantitative PCR and conventional culture on respiratory and blood specimens showed an overall prevalence of Streptococcus pneumoniae of 7.43%, ranking sixth. However, its ranking varied from third to seventh among the nine cities. (2) Challenges and concerns about viruses have increased. National surveillance of acute respiratory tract infections and epidemiology in China from 2009 to 2019 indicated that the positivity rates for viral infections in adult pneumonia was 20.5%. These rates were similar to the results of the CDC\'s CAP pathogen study in the United States, although the rankings were different (viruses ranked second in China and first in the United States). Over the past 20 years, the emergence of new viral respiratory infections caused by mutant strains or zoonotic strains has significantly increased the challenges and threats posed by viral respiratory infections. (3) The role of Mycoplasma pneumoniae (M pneumoniae) in adult CAP and the need for routine empirical antibiotic coverage are controversial. In addition to the influence of epidemic cycles, the prevalence of M pneumoniae is influenced by factors such as age, season, study design, and detection methods, and geographical distribution is also an important influencing factor. Although M. pneumoniae ranks first among CAP pathogens in mainland China (11.05%), there are significant regional differences. In Beijing, Xi\'an, and Changchun M. pneumoniae ranks first, while in Harbin, Nanjing, and Fuzhou it ranks second to sixth. In Wuhan, Shenzhen, and Chengdu M. pneumoniae ranks after the tenth position. Available evidence supports the notion that routine coverage of M. pneumoniae is not necessary for empirical treatment of CAP, except in severe cases. In regions with a high prevalence of M. pneumoniae, the decision to cover atypical pathogens in patients with mild to moderate CAP should be based on local data and individualized. (4) CAP caused by multidrug-resistant bacteria, especially multidrug-resistant Gram-negative bacilli (GNB), has become a concern. According to a systematic review of Chinese literature, Klebsiella pneumoniae accounted for 8.12% of adult CAP patients, ranking fifth, and Pseudomonas aeruginosa accounted for 4.7% (ninth). The China Antimicrobial Resistance Surveillance System (CARSS) reported an average resistance rate of 27.7% for Klebsiella pneumoniae to third-generation cephalosporins and a resistance rate of 10.0% to carbapenems in 2021. The average resistance rate of Pseudomonas aeruginosa to carbapenems was 16.6%. Early empirical treatment should consider predicting the resistance profile using a \"locally validated risk factor\" scoring system. (5) Co-infections are common but under-reported. The development of non-culture detection techniques over the past 40 years has significantly increased the detection rate of respiratory pathogens, especially viruses, leading to an increasing number of reports of bacterial-viral co-infections in CAP. It has been reported that co-infections account for 39% of severe CAP cases on ventilators in the ICU. Currently, there is inconsistency and confusion regarding the definition and concept of co-infection, the choice of detection techniques, and the differentiation between co-detection and co-infection. Many reports of co-infections in COVID-19 lacked pathogenic evidence, and some even listed \"effective antibiotic treatment\" as one of the diagnostic criteria for viral-bacterial co-infections, suggesting to some extent an overuse of antibiotics in COVID-19. Due to the diverse etiological spectrum of CAP between regions in the recent years, it is challenging to develop unified guidelines for the management of CAP in large countries. This article provides recommendations for the development of local guidelines for the diagnosis and treatment of CAP.
近二三十年来新发和再发感（传）染病频现、病原学分子检测技术进步、抗生素耐药、人群生活方式和免疫状态变化（包括疫苗接种）等原因，致CAP病原学发生新的演变。（1）肺炎链球菌虽然仍是CAP的常见病原体，但在中国和美国已不居首位。（2）病毒的挑战与困扰增加。（3）肺炎支原体在成人CAP的地位和经验性抗菌治疗常规覆盖的观点存在争议。（4）CAP多耐药菌特别多重耐药GNB感染受到关注。（5）共感染常见而报道混乱。由于CAP病原学演变呈现出多样化、地方化的趋势，给大国制订统一指南带来困难，本文对制订地方性CAP诊治指导意见提出建议。.

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.

OBJECTIVE: Severe community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCAP is of urgent need. The function of miR-486-5p in SCAP diagnosis and prognosis was evaluated to identify a promising biomarker for SCAP.
METHODS: The serum miR-486-5p in 83 patients with SCAP, 52 healthy individuals, and 68 patients with mild CAP (MCAP) patients were analyzed by PCR. ROC analysis estimated miR-486-5p in screening SCAP, and the Kaplan-Meier and Cox regression analyses evaluated the predictive value of miR-486-5p. The risk factors for MCAP patients developing SCAP were assessed by logistic analysis. The alveolar epithelial cell was treated with Klebsiella pneumonia to mimic the occurrence of SCAP. The targeting mechanism underlying miR-486-5p was evaluated by luciferase reporter assay.
RESULTS: Upregulated serum miR-486-5p screened SCAP from healthy individuals and MCAP patients with high sensitivity and specificity. Increasing serum miR-486-5p predicted the poor outcomes of SCAP and served as a risk factor for MCAP developing into SCAP. K. pneumonia induced suppressed proliferation, significant inflammation and oxidative stress in alveolar epithelial cells, and silencing miR-486-5p attenuated it. miR-486-5p negatively regulated FOXO1, and the knockdown of FOXO1 reversed the effect of miR-486-5p in K. pneumonia-treated alveolar epithelial cells.
CONCLUSIONS: miR-486-5p acted as a biomarker for the screening and monitoring of SCAP and predicting the malignancy of MCAP. Silencing miR-486-5p alleviated inflammation and oxidative stress induced by K. pneumonia via negatively modulating FOXO1.

The COVID-19 pandemic has altered the infection landscape for many pathogens. This retrospective study aimed to compare Haemophilus influenzae (H. influenzae) infections in pediatric CAP patients hospitalized before (2018-2019) and during (2020-2022) the COVID-19 pandemic. We analyzed the clinical epidemiology and antimicrobial resistance (AMR) patterns of H. influenzae from a tertiary hospital in southwest China. A total of 986 pediatric CAP patients with H. influenzae-associated infections were included. Compared to 2018, the positivity rate increased in 2019 but dropped significantly in 2020. Although it rose in the following 2 years, the rate in 2022 remained significantly lower than in 2019. Patients\' age during the pandemic was significantly higher than in 2018 and 2019, while gender composition remained similar across both periods. Notably, there were significant changes in co-infections with several respiratory pathogens during the pandemic. Resistance rates of H. influenzae isolates to antibiotics varied, with the highest resistance observed for ampicillin (85.9%) and the lowest for cefotaxime (0.0%). Resistance profiles to various antibiotics underwent dramatic changes during the COVID-19 pandemic. Resistance to amoxicillin-clavulanate, cefaclor, cefuroxime, trimethoprim-sulfamethoxazole, and the proportion of multi-drug resistant (MDR) isolates significantly decreased. Additionally, MDR isolates, alongside isolates resistant to specific drugs, were notably prevalent in ampicillin-resistant and β-lactamase-positive isolates. The number of pediatric CAP patients, H. influenzae infections, and isolates resistant to certain antibiotics exhibited seasonal patterns, peaking in the winter of 2018 and 2019. During the COVID-19 pandemic, sharp decreases were observed in February 2020, and there was no resurgence in December 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection spectrum of H. influenzae in pediatric CAP patients, as evidenced by shifts in positivity rate, demographic characteristics, respiratory co-infections, AMR patterns, and seasonal trends.