Guideline-Concordant Therapy for Community-Acquired Pneumonia in the Hospitalized Population: A Systematic Review and Meta-analysis.

Background: A commonly used guideline for community-acquired pneumonia (CAP) is the joint American Thoracic Society and Infectious Diseases Society of America practice guideline. We aimed to investigate the effect of guideline-concordant therapy in the treatment of CAP. Methods: We systematically searched MEDLINE, Embase, CENTRAL, Web of Science, and Scopus from 2007 to December 2023. We screened citations, extracted data, and assessed risk of bias in duplicate. Primary outcomes were mortality rates, intensive care unit (ICU) admission, and length of stay. Secondary outcomes were guideline adherence, readmission, clinical cure rate, and adverse complications. We performed random-effect meta-analysis to estimate the overall effect size and assessed heterogeneity using the I2 statistics. Results: We included 17 observational studies and 82 240 patients, of which 10 studies were comparative and pooled in meta-analysis. Overall guideline adherence rate was 65.2%. Guideline-concordant therapy was associated with a statistically significant reduction in 30-day mortality rate (crude odds ratio [OR], 0.49 [95% confidence interval .34-.70; I2 = 60%]; adjusted OR, 0.49 [.37-.65; I2 = 52%]) and in-hospital mortality rate (crude OR, 0.63 [.43-.92]; I2 = 61%). Due to significant heterogeneity, we could not assess the effect of guideline-concordant therapy on length of stay, ICU admission, readmission, clinical cure rate, and adverse complications. Conclusions: In hospitalized patients with CAP, guideline-concordant therapy was associated with a significant reduction in mortality rate compared with nonconcordant therapy; however, there was limited evidence to support guideline-concordant therapy for other clinical outcomes. Future studies are needed to assess the clinical efficacy and safety of current guideline recommendations.

Controversies in the management of community-acquired pneumonia in adults.

Community-acquired pneumonia (CAP) is a common infectious syndrome in Australia and a leading global cause of morbidity and mortality. It drives a significant amount of antimicrobial prescribing in Australia. Accurate assessment and stratification of CAP severity is important. However, adequate evaluation is challenging and controversy remains about the optimal method. Streptococcus pneumoniae is the most commonly identified bacterial pathogen causing CAP. As such, oral amoxicillin monotherapy is the mainstay of empirical therapy for low-severity CAP. The need to start empirical therapy for pathogens such as Mycoplasma pneumoniae and Legionella species in low-severity CAP remains controversial; evaluating the causative pathogen on clinical grounds alone is difficult. Oral antibiotics recommended for CAP (e.g. amoxicillin, doxycycline) have excellent bioavailability and may be used instead of intravenous therapy in some hospitalised patients. A duration of 5 days of antibiotic therapy is recommended in clinical practice guidelines for patients with uncomplicated CAP who meet stability criteria at follow-up.

Optimizing discharge antimicrobial therapy: Evaluation of a transitions of care process and electronic scoring system for patients with community-acquired pneumonia or chronic obstructive pulmonary disease.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Prescribing excess antibiotic duration at hospital discharge is common. A pharmacist-led Antimicrobial Stewardship Program Transition of Care (ASP TOC) intervention was associated with improved discharge prescribing. To improve the sustainability of this service, an electronic scoring system (ESS), which included the ASP TOC electronic variable, was implemented in the electronic medical record to prioritize pharmacist workload. The purpose of this study was to evaluate the implementation of the ASP TOC variable in the ESS in patients with community-acquired pneumonia (CAP) or chronic obstructive pulmonary disease (COPD). METHODS: This institutional review board-approved, retrospective quasi-experiment included patients discharged on oral antibiotics for CAP or COPD exacerbation (lower respiratory tract infection) from November 1, 2021, to March 1, 2022 (the preintervention period) and November 1, 2022, to March 1, 2023 (the postintervention period). The primary endpoint was optimized discharge antimicrobial regimen. A sample of at least 194 patients was required to achieve 80% power to detect a 20% difference in the frequency of optimized therapy. Multivariable logistic regression was used to identify factors associated with optimized regimens. RESULTS: Similar baseline characteristics were observed in both study groups (n = 100 for both groups). The frequency of optimized discharge regimens improved from 69% to 82% (P = 0.033). The percentage of ASP TOC interventions documented as completed by a pharmacist increased from 4% to 25% (P < 0.001). ASP TOC intervention, female gender, and COPD were independently associated with an optimized discharge regimen (adjusted odds ratios, 6.57, 1.61, and 3.89, respectively; 95% CI, 1.51-28.63, 0.81-3.17, and 1.85-8.20, respectively). CONCLUSION: After the launch of the ASP TOC variable, there was an increase in optimized discharge regimens and ASP TOC interventions completed. Pharmacists' use of the ASP TOC variable through an ESS can aid in improving discharge prescribing.

Comparison of NEWS2 and PSI as mortality predictors in patients with community acquired pneumonia.

In the West, National Early Warning Score 2 (NEWS2) is commonly applied to predict the severity of illness using only bedside variables unlike the extensive Pneumonia Severity Index (PSI). The objective of this study was to compare these scores as mortality predictors in patients admitted with community acquired pneumonia (CAP). This cross-sectional study was conducted in Jinnah Postgraduate Medical Centre, Karachi, Pakistan, for six months in 2020 on 116 patients presenting with CAP. Cases of aspiration pneumonia, hospital acquired pneumonia, pulmonary tuberculosis, pulmonary embolism, and pulmonary oedema were excluded. In-hospital mortality was taken as the outcome of this study. The mean age of the participants was 46.9±20.5 years. The in-hospital mortalities were 45(38.8%). NEWS2 was 97.8% sensitive but only 15.5% specific in predicting the outcome, whereas PSI was less sensitive (68.9%) but more specific (50.7%), which showed that in comparison with PSI, NEWS2 is a more sensitive mortality predicting score among hospitalised CAP patients.

Association between advanced lung cancer inflammation index and in-hospital mortality in ICU patients with community-acquired pneumonia: A retrospective analysis of the MIMIC-IV database.

Objective: The objective of the present study was to explore the correlation between the advanced lung cancer inflammation index (ALI) and in-hospital mortality among patients diagnosed with community-acquired pneumonia (CAP). Methods: Data from the Medical Information Mart for Intensive Care-IV database were adopted to analyze the in-hospital mortality of ICU patients with CAP. Upon admission to the ICU, fundamental data including vital signs, critical illness scores, comorbidities, and laboratory results, were collected. The in-hospital mortality of all CAP patients was documented. Multivariate logistic regression (MLR) models and restricted cubic spline (RCS) analysis together with subgroup analyses were conducted. Results: This study includes 311 CAP individuals, involving 218 survivors as well as 93 nonsurvivors. The participants had an average age of 63.57 years, and the females accounted for approximately 45.33%. The in-hospital mortality was documented to be 29.90%. MLR analysis found that ALI was identified as an independent predictor for in-hospital mortality among patients with CAP solely in the Q1 group with ALI ≤ 39.38 (HR: 2.227, 95% CI: 1.026-4.831, P = 0.043). RCS analysis showed a nonlinear relationship between the ALI and in-hospital mortality, with a turning point at 81, and on the left side of the inflection point, a negative correlation was observed between ALI and in-hospital mortality (HR: 0.984, 95% CI: 0.975-0.994, P = 0.002). The subgroup with high blood pressure showed significant interaction with the ALI. Conclusion: The present study demonstrated a nonlinear correlation of the ALI with in-hospital mortality among individuals with CAP. Additional confirmation of these findings requires conducting larger prospective investigations.

A Diagnostic Dilemma: A Case of Complicated Pneumonia With Pyelonephritis and Subclinical Myocarditis.

A 41-year-old woman presented with a 3.5-month history of fever, weakness, productive cough, and burning micturition along with generalized weakness and significant weight loss. Chest X-ray revealed bilateral infiltrates and bilateral pleural effusion, and the workup suggested community-acquired pneumonia (CAP). However, the course was complicated by persistent fevers, elevated inflammatory markers, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), and pelvic fluid collection. Extensive investigations, including bronchoscopy and lung biopsy, failed to identify a specific pathogen. Pulmonary vasculitis and lymphoma were ruled out. Antibiotic and corticosteroid therapy resulted in clinical improvement. While the cause remains unknown, brucellosis and aspergillosis were considered but ruled out with advanced testing. The underlying etiology remains elusive, highlighting the diagnostic challenges in CAP with atypical presentations.

Pneumonia in Geriatric Patients and Prediction of Mortality Based on the Pneumonia Severity Index (PSI), CURB-65, Frailty Index (FI), and FI-Lab21 Scores.

Background Elderly individuals have higher rates of morbidity, death, and financial burden due to community-acquired pneumonia (CAP). Objectives The study aimed to assess the outcomes of geriatric pneumonia patients and the prediction of mortality based on the pneumonia severity index (PSI), CURB-65 (confusion, urea, respiratory rate, blood pressure, and 65-year-old score), frailty index (frailty index), and FI-Lab21 (21-item frailty index based on laboratory) scores. Methods A prospective observational study was conducted on 100 elderly patients (≥ 65 years) with CAP. PSI, CURB-65, FI, and FI-Lab21 scores were determined. The outcome measures were 30-day mortality and the risk factors of mortality. The mortality predictive value of scores were compared. Results The mean age of the study subjects was 72.14 ± 6.1 years. Specifically, 76 (76%) were male, and 24 (24%) were females. During the follow-up, there was a 30-day mortality rate of 57%. On performing multivariate regression, the PSI score and severely frail were significant independent risk factors of mortality, with an odds ratio of 1.046 and 52.213, respectively. Area under the ROC curve (AUC) showed that the performance of the PSI score (AUC: 0.952; 95% CI: 0.910-0.994), CURB-65 score (AUC: 0.936; 95% CI: 0.893-0.978), and severely frail (AUC: 0.907; 95% CI: 0.851-0.962) was outstanding, while FI-Lab21 (AUC: 0.515; 95% CI: 0.400-0.631) was non-significant. Among all the parameters, the PSI score was the best predictor of mortality at the cutoff points of >121 with a diagnostic accuracy of 92%. Conclusion CAP in the elderly carries a high mortality rate. Out of PSI, CURB-65, FI, and FI-Lab21 scores, the PSI holds the best predicting ability for mortality.

A Single Lung Abscess Caused by Panton-Valentine Leukocidin-Producing Methicillin-Resistant Staphylococcus aureus.

This case report presents a rare occurrence of a single lung abscess caused by Panton-Valentine leukocidin (PVL)-producing methicillin-resistant Staphylococcus aureus (MRSA) in a 38-year-old immunocompetent man. The patient, of Southeast Asian origin, presented with symptoms of fever, chest pain, cough, and shortness of breath following a recent flu-like illness. Imaging indicated a cavitary lung lesion in the left lower lobe, suggestive of a lung abscess. Initial antibiotic treatment failed, and drainage of the abscess confirmed MRSA with the PVL gene, indicating a community-acquired MRSA infection. The patient received intravenous vancomycin followed by oral linezolid, leading to the resolution of the abscess. Contact tracing and decolonization measures were implemented. This case highlights the importance of considering PVL-producing S. aureus as a potential pathogen in severe necrotizing pneumonia or sepsis and underscores the need for prompt diagnosis, appropriate antibiotic therapy, and infection control measures in managing such infections.

The impact of the COVID-19 pandemic on Staphylococcus aureus infections in pediatric patients admitted with community acquired pneumonia.

The COVID-19 pandemic has significantly transformed the infection spectrum of various pathogens. This study aimed to evaluate the impact of the COVID-19 pandemic on Staphylococcus aureus (S. aureus) infections among pediatric patients with community acquired pneumonia (CAP). We retrospectively reviewed pediatric CAP admissions before (from 2018 to 2019) and during (from 2020 to 2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) profiles of S. aureus isolates were examined to assess the pandemic's effect. As a result, a total of 399 pediatric CAP patients with S. aureus infections were included. The positivity rate, gender, and age distribution of patients were similar across both periods. There was a marked reduction in respiratory co-infections with Haemophilus influenzae (H. influenzae) during the COVID-19 pandemic, compared to 2019. Additionally, there were significant changes in the resistance profiles of S. aureus isolates to various antibiotics. Resistance to oxacillin and tetracycline increased, whereas resistance to penicillin, gentamicin, and quinolones decreased. Notably, resistance to erythromycin significantly decreased in methicillin-resistant S. aureus (MRSA) strains. The number of S. aureus isolates, the proportion of viral co-infections, and the number of resistant strains typically peaked seasonally, primarily in the first or fourth quarters of 2018, 2019, and 2021. However, shifts in these patterns were noted in the first quarter of 2020 and the fourth quarter of 2022. These findings reveal that the COVID-19 pandemic has significantly altered the infection dynamics of S. aureus among pediatric CAP patients, as evidenced by changes in respiratory co-infections, AMR patterns, and seasonal trends.

Swab Testing to Optimize Pneumonia treatment with empiric Vancomycin (STOP-Vanc): study protocol for a randomized controlled trial.

Background: Vancomycin, an antibiotic with activity against Methicillin-resistant Staphylococcus aureus (MRSA), is frequently included in empiric treatment for community-acquired pneumonia (CAP) despite the fact that MRSA is rarely implicated in CAP. Conducting polymerase chain reaction (PCR) testing on nasal swabs to identify the presence of MRSA colonization has been proposed as an antimicrobial stewardship intervention to reduce the use of vancomycin. Observational studies have shown reductions in vancomycin use after implementation of MRSA colonization testing, and this approach has been adopted by CAP guidelines. However, the ability of this intervention to safely reduce vancomycin use has yet to be tested in a randomized controlled trial. Methods: STOP-Vanc is a pragmatic, prospective, single center, non-blinded randomized trial. Adult patients with suspicion for CAP who are receiving vancomycin and admitted to the Medical Intensive Care Unit at Vanderbilt University Medical Center will be screened for eligibility. Eligible patients will be enrolled and randomized in a 1:1 ratio to either receive MRSA nasal swab PCR testing in addition to usual care (intervention group), or usual care alone (control group). PCR testing results will be transmitted through the electronic health record to the treating clinicians. Primary providers of intervention group patients with negative swab results will also receive a page providing clinical guidance recommending discontinuation of vancomycin. The primary outcome will be vancomycin-free hours alive, defined as the number of hours alive and free of the use of vancomycin within the first seven days following trial enrollment estimated using a proportional odds ratio model. Secondary outcomes include 30-day all-cause mortality and time alive off vancomycin. Discussion: STOP-Vanc will provide the first randomized controlled trial data regarding the use of MRSA nasal swab PCR testing to guide antibiotic de-escalation. This study will provide important information regarding the effect of MRSA PCR testing and antimicrobial stewardship guidance on clinical outcomes in an intensive care unit setting. Trial registration: This trial was registered on ClinicalTrials.gov on February 22, 2024. (ClinicalTrials.gov identifier: NCT06272994).

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.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

The relationship between comprehensive geriatric assessment on the pneumonia prognosis of older adults: a cross-sectional study.

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. CONCLUSION: 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.

Adult Pneumococcal Vaccination in Ghana: Current Status and Future Recommendations - Expert Opinion.

Vaccination programs have proven successful in the prevention and control of infectious diseases among children on a global scale, but the majority of adult populations remain unvaccinated. immunocompromised adults as well as older adults aged low-income countries as Streptococcus pneumoniae infections are associated with substantial morbidity and mortality among 65 years and above. Despite the introduction of pneumococcal conjugate vaccines (PCVs), the burden of vaccine-type serotypes remains high in there are no clear policies for adult vaccination. As per the Global Burden of Disease 2019 report, about 120,000 individuals aged 70 years and older died as a result of LRTIs) in sub-Saharan Africa. A medical advisory board meeting was conducted in April 2022 to discuss the burden of pneumococcal diseases in adults, the current status of policies and practices of adult vaccination, unmet needs, and challenges in Ghana. This expert opinion paper outlines the pneumococcal epidemiology and burden of disease in Ghana, as well as the rationale for adult pneumococcal vaccination. It also highlights the potential barriers to adult vaccination and offers recommendations to overcome these obstacles and enhance vaccine acceptance in Ghana.

Les programmes de vaccination ont prouvé leur succès dans la prévention et le contrôle des maladies infectieuses chez les enfants à l'échelle mondiale, mais la majorité des populations adultes restent non vaccinées. Les infections à Streptococcus pneumoniae sont associées à une morbidité et une mortalité substantielles chez les adultes immunodéprimés ainsi que chez les personnes âgées de 65 ans et plus. Malgré l'introduction des vaccins conjugués contre le pneumocoque (VCP), la charge des sérotypes vaccinaux reste élevée dans les pays à faible revenu car il n'existe pas de politiques claires en matière de vaccination des adultes. Selon le rapport sur la charge mondiale de morbidité de 2019, environ 120 000 personnes âgées de 70 ans et plus sont décédées des suites d'infections des voies respiratoires inférieures (IVRI) en Afrique subsaharienne. Une réunion du conseil consultatif médical a eu lieu en avril 2022 pour discuter du fardeau des maladies pneumococciques chez les adultes, de l'état actuel des politiques et pratiques de vaccination des adultes, des besoins non satisfaits et des défis au Ghana. Cet article d'opinion d'experts présente l'épidémiologie pneumococcique et le fardeau de la maladie au Ghana, ainsi que les arguments en faveur de la vaccination pneumococcique des adultes. Il met également en lumière les obstacles potentiels à la vaccination des adultes et propose des recommandations pour surmonter ces obstacles et améliorer l'acceptation des vaccins au Ghana. MOTS-CLÉS: Maladie pneumococcique, Fardeau de la maladie, Vaccin conjugué contre le pneumocoque, Vaccination des adultes, Streptococcus pneumoniae, Ghana, Défis de la vaccination, Immunisation des adultes, VCP-13, Pneumonie acquise en communauté.

The etiological diagnostic value of metagenomic next-generation sequencing in suspected community-acquired pneumonia.

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.

Enhancing pathogen description and antibiotic regimen selection in community-acquired pneumonia through RT-qPCR assays.

Background: Adults with community-acquired pneumonia (CAP) in China suffer high morbidity. CAP is caused by a multitude of pathogens; however, pathogen-directed clinical symptoms are often lacking. Therefore, patients lacking an accurate microbiological diagnosis are administered with empirical antimicrobials. Methods: We collected bronchoalveolar lavage fluid, as well as clinical and laboratory data from 650 adult patients with CAP admitted to three hospitals in Hubei, Sichuan, and Zhejiang provinces in China. Specimens were cultured and tested using real-time reverse transcription qPCR (RT-qPCR) assays for the presence of 42 respiratory bacteria and viruses. CAP was investigated with respect to regions, genders, and age and patterns of infections or co-infections. Employing clinical guidelines adapted for diagnosis, we assessed retrospectively the appropriate pathogen-directed therapy and compared it with the initial empirical therapies. Results: Our study identified that 21.38% (139/650) of the patients were classified as having Severe CAP (S-CAP), with a higher prevalence among males, older adults, and during the warm season. Bacterial pathogens were detected in 35.53% (231/650) of cases. K. pneumoniae, H. influenzae, and S. aureus were the most prevalent bacteria across different demographics and regions. Viral pathogens were found in 48.76% (317/650) of patients Epstein-Barr, Human rhinovirus, and Cytomegalovirus were the most common viruses. Co-infections were present in 24.31% (158/650) of cases, with viral-bacterial co-infections being the most frequent. The RT-qPCR demonstrated significantly higher detection rates for key pathogens compared to standard culture methods. It showed potential in optimizing antimicrobial prescriptions by allowing for de-escalation in 18.30% (95/518) of patients, among which reducing the number of excessive antibiotics mainly comprised decreasing the use of 2nd or 3rd generation cephalosporins (5.79%, 30/518) and ß-lactamase inhibitor combinations. Conclusion: The study highlights the significant burden of S-CAP, particularly among specific demographics and seasons. The prevalence of bacterial and viral pathogens, along with the high rate of co-infections, emphasizes the need for comprehensive diagnostic approaches. The RT-qPCR assays emerge as a superior diagnostic tool, offering enhanced pathogen detection capabilities and facilitating more precise antimicrobial therapy. This could lead to improved patient outcomes and contribute to the rational use of antimicrobials, addressing the growing concern of antibiotic resistance.

Epidemiology and risk factors of community-acquired pneumonia in patients with different causes of immunosuppression.

Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated.We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities.942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3-2.5]) and consecutive death (HR 1.9[1.8-2.1]). Organ and stem cell transplantation (HR 3.2[2.6-4.0] and 2.8[2.1-3.7], respectively), HIV (HR 3.2[1.9-5.4]) and systemic steroids (> 20 mg prednisone daily dose equivalent (HR 2.7[2.4-3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0-24.5]), especially HIV (HR 34.1[7.6-153]) and systemic steroids (HR 8.2[4.6-14.8]).Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.