BACKGROUND: Pneumonia is a common infection that leads to frequent hospitalizations and primary healthcare visits. Previous smaller studies have indicated high prevalence of undiagnosed diabetes mellitus (DM) and increased subsequent risk of coronary heart disease (CHD) among patients with pneumonia. However, previous studies have not used nationwide data that include diagnoses from primary healthcare settings, where most pneumonias are treated. The aim of this study was to examine whether pneumonia is associated with subsequent DM and CHD. METHODS: This was an open nationwide cohort study of adults 35–75 years of age in Sweden 2007–2018, including national registers and population-based primary healthcare data. The outcomes were DM and CHD, and individuals with outcomes diagnosed before the index date (including 2002–2005) were excluded. The index date was set as the first pneumonia diagnosis or the first healthcare contact (in those without pneumonia) during the study period. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. RESULTS: A total of 4,580,606 individuals without previously diagnosed DM and 4,661,052 individuals without previously diagnosed CHD were included; of these, 348,024 individuals were diagnosed with DM and 295,592 with CHD during follow-up, respectively. Pneumonia preceded DM in 104,598 (30.1%) and CHD in 94,087 (31.8%) individuals. Compared with no diagnosis, pneumonia was associated with an age-adjusted HR of 1.12 (95% CI 1.11–1.13) for DM and 1.18 (95% CI 1.17–1.19) for CHD. In the full model, pneumonia was associated with a HR of 1.11 (95% CI 1.10–1.12) for both outcomes. Several complementary analyses were conducted, showing significant associations across most age-groups, in both sexes, across different follow-up periods (e.g. <1 year and ≥ 10 years), and in patients diagnosed with pneumonia in primary healthcare settings. CONCLUSIONS: This nationwide study found that pneumonia is associated with subsequent DM and CHD. The findings indicate that pneumonia has a potential role as a clinical predictor of DM or CHD, including in primary healthcare settings, which warrants further clinical studies.
BACKGROUND: Paediatric pneumonia remains a significant public health concern globally, and the risk factors for pneumonia and carriage vary across different populations. The accuracy of pneumococcal urinary antigen test (PUAT) remains unclear. We aimed to determine the prevalence of pneumococcal carriage, and the risk factors associated with pneumonia and carriage among children aged under 5 years in Peninsular Malaysia, and to evaluate the performance of the PUAT at detecting pneumococcal carriage. MATERIALS AND METHODS: A total of 500 cases of pneumonia and 500 age-matched controls at three tertiary hospitals across three states in Peninsular Malaysia were recruited from October 2021 to August 2023. Nasopharyngeal swabs (NPS) were taken to test for Streptococcus pneumoniae (Spn) using culture and multiplex-PCR while urine samples were collected for PUAT with BinaxNOW®. Logistic regression analyses were fitted for paediatric pneumonia and pneumococcal carriage risk factors. RESULTS: The overall prevalence of nasopharyngeal pneumococcal carriage was 15.4% (n = 154) based on culture and optochin susceptibility, with identical rates observed among children with pneumonia and healthy controls. PUAT positivity was higher among pneumonia cases (11.8%, 59/500) than the controls (8.8%, 44/500) but was not statistically significant (p = 0.119). The carriage prevalence was significantly higher in the east coast (19.5%) compared to the central west coast (9.5%) (p < 0.001). Significant predictors of pneumonia were having siblings aged under 5 years (p = 0.002), pre-existing illness (p < 0.001), exposure to indoor smoking (p = 0.01), overcrowding (p = 0.012), underweight (p = 0.001) and obesity (p = 0.023). The predictors of pneumococcal carriage were recruiting sites and pneumococcal vaccination status. Compared to culture and PCR, the sensitivity and specificity of BinaxNOW® to detect Spn in urine were similar at about 31% and 93%, respectively. CONCLUSION: Pneumococcal carriage prevalence was similar in pneumonia cases and healthy controls, and the true burden of pneumococcal pneumonia in Malaysia remains unknown. Our findings identified risk factors for childhood pneumonia and pneumococcal carriage that are consistent with those reported elsewhere. The BinaxNOW® showed low sensitivity and moderate specificity indicating its limited utility as a standalone diagnostic tool for Spn detection in clinical settings. A focus should be made to recognise risk profiles to support early identification, timely intervention, and prevention strategies for respiratory infections in vulnerable paediatric populations. There is a need for continued Spn carriage surveillance and ongoing research to improve diagnostics to guide public health strategies for the prevention of pneumococcal infections.
An increase in hospitalizations for respiratory illnesses due to Mycoplasma pneumoniae was reported in France in late October 2023. Data in primary care are scarce and microbiological or radiological investigations are not routinely recommended for community-acquired pneumonia. We computed weekly incidence rates of pneumonia and bronchiolitis cases from the electronic records of French general practitioners from January 2016 to August 2024. These weekly incidences were described in the light of the Covid-19 pandemic, overall and by age group. For better interpretation, the weekly incidences of pneumonia and bronchiolitis were compared with virological surveillance data of acute respiratory infections observed in general practice. During the 2016-2024 period, 108,539 cases of pneumonia and 46,411 cases of bronchiolitis were identified from 51,351,414 consultations. The incidence of pneumonia consultations in general practice during the 2022-2023 and 2023-2024 seasons is similar to that observed before the Covid-19 pandemic, after two seasons of low incidence (2020-2021 and 2021-2022). However, the 2023-2024 pneumonia epidemic is the strongest ever observed in children (0-14 years, and especially among the 5-14 years) in general practice since 2016, with an earlier onset. Regarding the incidence of bronchiolitis in children, the 2023-2024 season was in line with the 2021-2022, 2022-2023 and pre-pandemic seasons. No abnormal circulation of classical seasonal viruses was observed during the 2023-2024 season. The sharp increase in pneumonia cases observed this season among children in primary care settings requires the implementation of studies to understand the cause and to confirm or refute the possible association with M. pneumoniae as observed in hospitals. Given the impact of the Covid-19 pandemic on the circulation of pathogens, it would be useful to extend, even on a temporary basis, the traditional microbiological surveillance in primary care to include common bacterial pathogens affecting the upper and lower respiratory tract, such as M. pneumoniae, S. pneumoniae or Streptococcus A.
Streptococcus pneumoniae is an important cause of pneumonia in older adults, however, serotyping and indirect impact information from low and middle-income countries is lacking. Mongolia has a childhood 13-valent pneumococcal conjugate vaccine (PCV13) program, but no adult pneumococcal vaccination program. We describe pneumococcal carriage rates, disease and serotype distribution among adults hospitalised with pneumonia, and explore changes over the COVID-19 pandemic period. Adults (≥ 18 years) hospitalised with clinical pneumonia were enrolled over 3 years (March 2019-February 2022) into a prospective pneumonia surveillance program. Nasopharyngeal swabs were tested to detect pneumococci using lytA qPCR and molecular serotyping by DNA microarray and metagenomics. Pneumococcal pneumonia was identified using serotype-specific urinary antigen detection and BinaxNOW® assays. Pneumococcal carriage and pneumonia prevalence were assessed over the COVID-19 period with log-binomial regression used to estimate prevalence and adjusted prevalence ratios (pre- versus early- and late-COVID-19 periods). Of 3,178 pneumonia cases, S. pneumoniae was identified in 12.1% (333/2,759) of swabs and 8.6% (253/2,925) of urine samples. PCV13 serotype carriage prevalence was 3.1% (82/2,663) and non-PCV13 serotype carriage prevalence 5.7% (152/2,663). In the late-COVID-19 period, pneumococcal carriage prevalence was reduced by 66% (aPR 0.34, 95%CI 0.25-0.46) and pneumococcal pneumonia by 82% (aPR 0.18, 95%CI 0.12-0.27) compared with the pre-COVID-19 transmission period. Despite paediatric vaccination with high coverage, we identified some residual PCV13 serotypes with predominance of non-PCV13 serotypes carried and causing disease in adults. Direct adult vaccination which targets these serotypes will potentially reduce disease in adults in Mongolia.
BACKGROUND: Undernutrition significantly increases the risk of severe infections and mortality in children under five, particularly in low- and middle-income countries. Pneumonia, a leading cause of childhood death, is especially dangerous in undernourished children, yet prognostic measures to identify those at highest risk are lacking. OBJECTIVE: To identify algorithms of poor prognosis in undernourished children with clinical pneumonia for early identification of children at risk for poor outcomes. METHODS: This study analyzed a subset of children enrolled in a cohort designed to identify biomarkers of bacterial pneumonia. Children aged 2–59 months with clinical pneumonia were recruited from two rural Gambian hospitals. Clinical and anthropometric data were collected at baseline, during hospitalization, and at 30-day follow-up. Nutritional status was classified using WHO definitions for stunting (height-for-age Z-scores) and wasting (weight-for-height Z-scores) as severe (Z-scores ≤ -3), moderate (-2 ≥ Z-scores > -3), and mild (-1 ≥ Z-scores > -2). Prognostic outcomes were classified into good and poor. Poor prognosis included death, prolonged hospital stay (≥ 7 days), post-discharge care-seeking, and difficult to feed during admission. Good prognosis was based on a hospital stay < 3 days, with good outcomes within 30 days of the initial visit. Classification tree models and penalized logistic regression models (fit through elastic net) were used to identify combinations of predictors of poor prognosis (prognostic signatures). RESULTS: A total of 246 children with clinical pneumonia and undernutrition (wasting or stunting) were included. Children with poor prognosis presented more frequently with respiratory distress, hypoxemia, reduced capacity oforal feeding difficulty, and anemia. As expected, undernutrition was associated with adverse outcomes. The final prognostic algorithms were accurate to identify undernourished children at risk of poor prognosis: with sensitivity and specificity > 80% and area under the receiver operating characteristic curve ≥ 0.80. Furthermore, we identified accurate prognostic signatures among children with both wasting and stunting. CONCLUSION: Measures collected at admission in undernourished children with clinical pneumonia can identify those at risk of poor outcomes. The prognostic signatures developed in this study may inform early risk stratification and guide timely intervention, particularly in resource-limited settings.
Aspiration pneumonia (AP) in older persons is associated with oropharyngeal dysphagia (OD) and is estimated to account for 5-15% of cases of community-acquired pneumonia (CAP). Artificial Intelligence Massive Screening for OD (AIMS-OD) is an algorithm for identifying OD in older patients on hospital admission using data from electronic health records (EHR). We aimed to assess the prevalence of OD among older patients hospitalized with pneumonia and thus estimate the underdiagnosis of AP based on AIMS-OD. A retrospective observational study included 15,603 patients older than 65 years who were admitted for pneumonia to a general hospital between 2013 and 2022. Clinical data were obtained from EHR. AIMS-OD is an accurate diagnostic algorithm (AUCROC > 0.79, specificity 0.92, PPV 0.86, NPV 0.58) for OD using AI and machine learning. a) AP prevalence following traditional clinical practice (ICD-10 J69.0, AP codification) on discharge was 15.57% (n=2,430, 86.73±7.43 years); b) Estimated AP prevalence related to OD identified with AIMS-OD, was 25.32% (n=3,951, 85.11±8.78 years); c) AIMS-OD identified 84.77% (n=2,060, 87.17±7.09 years) of clinically diagnosed patients (ICD-10 J69.0), and 1,891 additional cases of AP (82.87±9.84 years) undetected by clinical practice, distinguishing them from pneumonia patients without OD in seconds.  CONCLUSION: The prevalence of AP following traditional clinical practice among older patients hospitalized with pneumonia was 15.57%. AIMS-OD revealed a potential prevalence of AP of 25.32%. AIMS-OD allows to increase by 62.6% the detection of AP related to OD versus traditional clinical practice among older patients hospitalized with pneumonia. AIMS-OD allows massive, immediate, and accurate identification of OD on hospital admission, from which AP cases can be identified, enabling early and specific treatment to improve the poor clinical outcomes of these unrecognized patients with AP and prevent its recurrence.
INTRODUCTION: Pneumonia is one of the most common and deadly infectious diseases affecting under-five children, responsible for about 15% of all deaths in this age group worldwide. In Ethiopia, the prevalence ranges from 16% to 21%, contributing substantially to under-five mortality. Despite national child survival efforts, pneumonia-related deaths remain a major public health concern. Understanding the burden and identifying key risk factors are essential for effective prevention and timely intervention. This study aimed to estimate the time to death and identify its predictors among under-five children with acute pneumonia using Bayesian parametric survival analysis. METHODS: A retrospective study was conducted with 451 under-five children diagnosed with acute pneumonia. Three survival analysis models were applied: the Cox proportional hazards model, the parametric accelerated failure time (AFT) model, and the Bayesian parametric survival model. In the Bayesian model, Markov Chain Monte Carlo (MCMC) methods such as Gibbs sampling and the Metropolis-Hastings algorithm were employed to obtain samples from the posterior distributions of the parameters. Each model was evaluated using appropriate model selection criteria to identify the best-fitting approach. RESULTS: The Bayesian Lognormal AFT model identified several significant predictors of time to death among under-five children with acute pneumonia. All model parameters showed good convergence, with Monte Carlo errors under 5% of their standard deviations. Female children had shorter survival times compared to males (AF = 0.46; 95% CI: 0.36–0.97). Children aged 1–11 months had better survival outcomes (AF = 0.10; 95% CI: 0.05–0.21) than those aged 48–59 months. Rural residence (AF = 1.48; 95% CI: 1.03–2.09), diagnosis during spring (AF = 0.73; 95% CI: 0.52–0.92) and summer (AF = 0.66; 95% CI: 0.49–0.84), comorbidities (AF = 1.26; 95% CI: 1.03–1.65), severe acute malnutrition (AF = 0.26; 95% CI: 0.13–0.43), anemia (AF = 0.88; 95% CI: 0.73–0.93), low weight (AF = 0.72; 95% CI: 0.55–0.90), and home delivery (AF = 0.75; 95% CI: 0.59–0.95) were all associated with reduced survival times. CONCLUSION: This study identified key predictors of mortality among under-five children with acute pneumonia using a Bayesian parametric survival model. Female, rural residence, severe acute malnutrition, comorbidity, anemia, and low weight were significantly associated with reduced survival times. Seasonal variation and place of delivery also influenced mortality, highlighting the impact of environmental and health system factors. These findings emphasize the need for targeted interventions focusing on early diagnosis, nutritional support, and tailored care for high-risk groups. Furthermore, the Federal Ministry of Health could enhance community awareness of early pneumonia detection and effective home management, particularly in rural areas where mortality risk is higher.
BACKGROUND: Pneumonia remains a leading cause of morbidity and mortality globally, necessitating reliable clinical prediction tools to guide medical management decisions. The Pneumonia Severity Index (PSI), CURB-65, and CRB-65 are clinical scoring tools used to assess the severity of community-acquired pneumonia (CAP), aiding in risk stratification and guiding decisions on hospitalization, level of care and prognosis. Comparative data on their utility, specifically in immunocompetent patients hospitalized in internal medicine wards, are limited. This study aimed to evaluate the predictive capabilities of these scoring tools for mortality and intensive care unit (ICU) transfers in a large cohort of hospitalized patients. METHODS: We conducted a retrospective, single-center cohort study including 12,670 immunocompetent patients hospitalized with pneumonia in the internal medicine division. PSI, CURB-65, and CRB-65 performance was compared across multiple outcomes, including in-hospital mortality, 30-, 60-, 90-day mortality, and ICU transfer from ward. Subgroup analyses were performed for key comorbidities (chronic obstructive pulmonary disease [COPD], congestive heart failure [CHF], diabetes, chronic kidney disease [CKD] and hypertension). RESULTS: PSI consistently demonstrated significantly superior discrimination between survivors and non-survivors across all mortality outcomes with AUC range of 0.73–0.75 (p < 0.001, FDR-corrected). In the subgroup analysis by comorbidities, PSI was significantly superior to the other scoring systems only in diabetes patients in 60 and 90-day mortality (AUC = 0.70–0.71). CURB-65 performed comparably to PSI in most of the cases and was superior to CRB-65 only in diabetes and hypertension patients. When predicting ICU transfer during hospitalization, there were no significant differences between the scoring tools, and all demonstrated low predictive capability. CONCLUSION: The PSI demonstrates superior discriminative ability in immunocompetent patients hospitalized with pneumonia. However, its greater complexity should be considered when evaluating its practicality for routine use.
To ascertain the role of the lung microbiome in the development of severe pneumonia and its potential as a biomarker for disease progression. BAL samples from 34 adults with severe community-acquired pneumonia (CAP) (17 viral, 8 viral coinfected with bacteria and 9 bacterial) admitted to the ICU for acute respiratory failure between 2019 and 2021 were collected within the first 48 h of admission to the ICU. The microbiome was characterized via the Ion 16S Metagenomics Kit and the Ion Torrent sequencing platform. Clinical factors, including survival, mechanical ventilation duration, blood biomarkers and organ failure in terms of acute respiratory distress syndrome (ARDS), shock or acute renal failure, were correlated with microbiome characteristics. The microbiome diversity in patients with viral pneumonia was significantly greater than that in patients with bacterial or coinfected pneumonia: the Shannon diversity index was 3.75 (Q1-Q3: 2.5-4.1) versus 0.4 (Q1-Q3: 0.2-1.3) and 0.48 (Q1-Q3: 0.3-1.1), respectively (p < 0.05). The microbiome diversity index was associated with severity-of-illness (APACHE II), independent of the etiology of pneumonia (B coefficient -1.845; p < 0.01). Patients with severe viral CAP who developed ARDS had a lower presence of Proteobacteria, and those who were complicated with ventilator-associated pneumonia had a higher prevalence of Acinetobacter at admission. The mortality of patients with bacterial or coinfected pneumonia was 35%. In coinfected patients, the diversity index was associated with the development of shock. Patients with severe CAP have low respiratory microbiome diversity, indicating that respiratory microbiome diversity is a potential biomarker of disease severity.
The 2019 American Thoracic Society and Infectious Diseases Society of America community acquired pneumonia guidelines recommend empiric coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa based on previous respiratory isolation, recent IV antibiotic use, and locally validated risk factors. This study aims to describe how local risk factors may be determined efficiently using data retrieved electronically. This retrospective cohort study focused on the time period May 13, 2020, through June 30, 2024. Consecutive adults admitted to one of five acute care facilities with confirmed community-acquired pneumonia were included. Community-acquired pneumonia was defined as the presence of one or more pneumonia diagnosis codes and an order for a respiratory culture or an antimicrobial with the indication of pneumonia or sepsis, 24 h before or within 48 h after the date and time of admission. Patients were excluded if they had a diagnosis code for hospital-acquired or ventilator-associated pneumonia, any subsequent admission in the study period, or if they had a previous respiratory culture positive for methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa within a year of admission. The causative pathogen and the presence or absence of evaluated risk factors were electronically abstracted from billing data and health records. Serial quality assessments of electronic data were performed to improve accuracy until a well validated population was determined. There were 4,558 unique patients included. Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa rates were 0.6% and 0.7%, respectively. Only age was inversely associated with risk of methicillin-resistant Staphylococcus aureus (OR = 0.86, 95% CI: 0.76-0.98). No significant risk factors for Pseudomonas aeruginosa were found. In rural or otherwise resource limited healthcare settings, risk factors for methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa community-acquired pneumonia may be determined using only electronic data capture and the methodology described in this article.
Nucleic acid amplification tests (NAATs) greatly enhance the capacity to identify the etiology of pediatric complicated pneumonia. However, the use of pneumococcal conjugate vaccines could reduce the importance of Streptococcus pneumoniae in pediatric complicated pneumonia with the potential emergence of other bacterial agents. Using an expanded NAAT in culture negative pleural fluid or empyema samples collected in 2010-2024 (n = 554) in Portugal, we show that S. pneumoniae remains the most frequent agent despite decades of pneumococcal conjugate vaccine use and the COVID-19 pandemic. A rebound in pediatric complicated pneumonia occurred post-pandemic, including a rise in cases by Streptococcus pyogenes and Haemophilus influenzae. Empiric therapy of pediatric complicated pneumonia should still consider S. pneumoniae as the most likely cause, even in countries where the pneumococcal conjugate vaccine is in the national immunization program with a high uptake.
Pneumonia remains a significant global health concern, particularly among those requiring admission to the intensive care unit (ICU). Despite the availability of international guidelines, there remains heterogeneity in clinical management. The D-PRISM study aimed to develop a global overview of how pneumonias (i.e., community-acquired (CAP), hospital-acquired (HAP), and Ventilator-associated pneumonia (VAP)) are diagnosed and treated in the ICU and compare differences in clinical practice worldwide. The D-PRISM study was a multinational, survey-based investigation to assess the diagnosis and treatment of pneumonia in the ICU. A self-administered online questionnaire was distributed to intensive care clinicians from 72 countries between September to November 2022. The questionnaire included sections on professional profiles, current clinical practice in diagnosing and managing CAP, HAP, and VAP, and the availability of microbiology diagnostic tests. Multivariable analysis using multiple regression analysis was used to assess the relationship between reported antibiotic duration and organisational variables collected in the study. A total of 1296 valid responses were collected from ICU clinicians, spread between low-and-middle income (LMIC) and high-income countries (HIC), with LMIC respondents comprising 51% of respondents. There is heterogeneity across the diagnostic processes, including clinical assessment, where 30% (389) did not consider radiological evidence essential to diagnose pneumonia, variable collection of microbiological samples, and use and practice in bronchoscopy. Microbiological diagnostics were least frequently available in low and lower-middle-income nation settings. Modal intended antibiotic treatment duration was 5-7 days for all types of pneumonia. Shorter durations of antibiotic treatment were associated with antimicrobial stewardship (AMS) programs, high national income status, and formal intensive care training. This study highlighted variations in clinical practice and diagnostic capabilities for pneumonia, particularly issues with access to diagnostic tools in LMICs were identified. There is a clear need for improved adherence to existing guidelines and standardized approaches to diagnosing and treating pneumonia in the ICU. Trial registration As a survey of current practice, this study was not registered. It was reviewed and endorsed by the European Society of Intensive Care Medicine.
Streptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced. A total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response. S. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406). In almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine.
Pneumococcal pneumonia is a common disease with a significant impact on morbidity and mortality among the elderly population. The main purpose of this meta-analysis was to estimate the prevalence of community-acquired pneumonia (CAP) in elderly individuals caused by Streptococcus pneumoniae (S. pneumoniae). A systematic search of the PubMed, Web of Science, and Scopus databases was conducted for relevant studies published between January 2013 and December 2023. Subgroup analysis and meta-regression were used to identify the sources of heterogeneity affecting the 87,430 patient studies obtained from 47 papers that met the inclusion and exclusion criteria. The combined prevalence rate for S. pneumoniae among all CAP patients included in the study was 14.8% (95% confidence interval [CI]: 12.3-17.8%). The 5-year pooled prevalence decreased from 16.5% (95% CI: 15.0-18.2%) in 1996-2000 to 8.4% (95% CI: 6.3-11.0%) in 2016-2020 for bacterial culture alone and from 17.4% (95% CI: 16.3-18.7%) to 13.5% (95% CI: 10.7-16.8%) for bacterial culture and urinary antigen testing (UAT) combined (P < 0.001). The most prevalent serotype was serotype 3, followed by serotypes 8, 19 A, 22 F, 11 A, 5, 9 N, 12 F, 6 A, and 10 A. The vaccine-serotype coverage was 53.5% for PCV 13, 60.5% for PCV 15, 85.2% for PCV 20 and 88.6% for PPSV 23. These findings indicate a decrease in the overall burden of pneumococcal CAP among elderly individuals over the decade, which lends support to the proposition that the delivery of immunization should be expanded across the life course.
A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population. We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: "regular" users (≥ 4 prescriptions), "irregular" users (1-3 prescriptions) and "non-users" (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models. A total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6-82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04-1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25-1.55). We also observed a small increased risk for all-cause mortality in the "regular ICS user" group compared with the "non-user" control group (HRadj = 1.19, 1.06-1.33). We found no evidence of an association between PPI prescribing and all-cause mortality. Prolonged prescription of medications used to treat common comorbidities in IPF may be associated with increased risks for severe respiratory infections. These findings point to a need to adopt an adequate risk-benefit balance approach to the prescribing of ICS-containing inhalers and PPIs in people with IPF without evidence of comorbidities, especially older patients and/or those with more advanced disease in whom respiratory infections are more likely to result in poorer outcomes.
Pneumococcal pneumonia continues to be a significant global health burden, affecting both children and adults. Traditional diagnostic methods for sputum analysis remain challenging. The objective of this study was twofold: to develop a rapid and easy-to-perform assay for the identification of Streptococcus pneumoniae (Spn) directly in sputum specimens using fluorescence microscopy, and to characterize with high-resolution confocal microscopy the ultrastructure of pneumococci residing in human sputum. We fluorescently labeled antibodies against the pneumococcal capsule (Spn-FLUO). The specificity and sensitivity of Spn-FLUO for detecting Spn was evaluated in vitro and in vivo using mouse models of carriage and disease, human nasopharyngeal specimens, and sputum from patients with pneumococcal pneumonia. Spn was confirmed in the specimens using culture and a species-specific qPCR assay. Spn strains were serotyped by Quellung. Confocal microscopy and Imaris software analysis were utilized to resolve the ultrastructure of pneumococci in human sputum. Compared with cultures and qPCR, Spn-FLUO demonstrated high sensitivity (78-96%) in nasopharyngeal samples from mice and humans. The limit of detection (LOD) in nasopharyngeal samples was ≥ 1.6 × 10⁴ GenEq/ml. The specificity in human nasopharyngeal specimens was 100%. In lung specimens from mice infected with pneumococci, Spn-FLUO reached 100% sensitivity with a LOD of ≥ 1.39 × 10⁴ GenEq/ml. In human sputum, the sensitivity for detecting Spn was 92.7% with a LOD of 3.6 × 10³ GenEq/ml. Ultrastructural studies revealed that pneumococci are expectorated as large aggregates with a median size of 1336 μm². Spn-FLUO is a rapid and sensitive assay for detecting Spn in human sputum within 30 min, encompassing a range of both vaccine and non-vaccine serotypes associated with pneumococcal pneumonia. The study highlights that most pneumococci form aggregates in human sputum.
Community-acquired pneumonia (CAP) causes substantial morbidity and mortality, particularly in patients with chronic obstructive pulmonary disease (COPD). This study compares the microbial detections in CAP patients with and without COPD using culture based and molecular diagnostic methods. This prospective study included 412 hospitalized pneumonia patients (136 with COPD). Lower respiratory tract samples were analysed with traditional cultures and a multiplex PCR panel (FilmArray Pneumonia Panel Plus). Multivariable Poisson regression identified predictors of Pseudomonas aeruginosa detection, and logistic regression estimated detection probability using the top predictors. Overall pathogen detection rates were similar between groups, but P. aeruginosa was significantly more common in COPD patients (12.5% vs. 3.1%; p < 0.001). In adjusted analyses, each additional year of age increased the risk of P. aeruginosa by 5% (RR 1.05; 95% CI 1.01-1.09), while advanced COPD (GOLD 3-4) conferred a four-fold higher risk (RR 4.29; 95% CI 1.94-9.46), diabetes mellitus a four-fold risk (RR 4.04; 95% CI 1.97-8.29), and prior P. aeruginosa detection a five-fold risk (RR 5.03; 95% CI 2.44-10.36). Inhaler use, bronchiectasis, and recent hospitalization were not independently associated. Although overall microbial detection rates were comparable between groups, P. aeruginosa was disproportionately prevalent in high-risk COPD individuals. While most COPD patients with pneumonia can be managed with standard empirical antibiotics, empirical coverage for P. aeruginosa should be considered for selected high-risk patients. Prospective studies are warranted to evaluate targeted P. aeruginosa coverage to optimize antibiotic stewardship and improve outcomes.
BACKGROUND: Severe community-acquired pneumonia (sCAP) is a major contributor to global hospital mortality, with some patients rapidly progressing to death within a few days due to acute respiratory distress syndrome (ARDS), septic shock, or multiorgan failure (MOFS). Despite the significant health burden, these cases remain poorly defined, often overlooked in clinical practice, and insufficiently addressed in existing guidelines. METHODS: In this multicenter retrospective study, we analyzed 1,517 hospitalized patients with sCAP for assessing the incidence of fulminant pneumonia -defined as sCAP leading to death within 7 days from hospital admission- and to identify factors associated with either an increased or reduced risk of unfavorable outcome. RESULTS: Our findings revealed a 5.9% incidence of fulminant pneumonia, with early death primarily due to ARDS (93%), sepsis (70%), and MOFS (73%). Older age, obesity, diabetes, cardiovascular disease, and elevated serum creatinine were associated with increased risk, while early corticosteroid administration was associated with a significant mortality reduction within seven days, both in the univariate and multivariate analyses (OR 0.22, CI 95% 0.12–0.38, p < 0.001). Baseline respiratory impairment and inflammatory markers were not associated with early mortality. CONCLUSION: These findings highlight the importance of recognizing sCAP as a time-dependent condition, requiring early identification and treatment of cases at risk for developing fulminant pneumonia at hospital admission. Larger studies and randomized controlled trials are necessary to validate these findings and optimize treatment strategies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT06516601.
Current guidelines recommend empiric antibiotic therapy for patients who require hospitalization for community-acquired pneumonia (CAP). We sought to determine whether clinical, imaging or laboratory features in patients hospitalized for CAP in whom PCR is positive for a respiratory virus enable exclusion of bacterial coinfection so that antibiotics can be withheld. For this prospective study, we selected patients in whom an etiologic diagnosis was likely to be reached, namely those who provided a high-quality sputum sample at or shortly after admission, and in whom PCR was done to test for a respiratory virus. We performed quantitative bacteriologic studies on sputum to determine the presence of bacterial infection or coinfection and reviewed all clinical, imaging and laboratory studies. Of 122 CAP patients studied, 77 (63.1%) had bacterial infection, 16 (13.1%) viral infection, and 29 (23.8%) bacterial/viral coinfection. Underlying pulmonary disease and a history of smoking were more common in bacterial pneumonia. Upper respiratory symptoms were more common, and mean white blood cell (WBC) counts were lower viral pneumonia. Nevertheless, no clinical, laboratory or imaging findings allowed exclusion of bacterial coinfection in patients who tested positive for a respiratory virus. In fact, patients with bacterial/viral coinfection were sicker than those with bacterial or viral pneumonia; 30% were admitted required transfer to the ICU during their hospital course, compared to 17% and 19% of patients with bacterial or viral infection, respectively (p < .05). In this study, 64.4% of patients who tested positive for a respiratory virus had a bacterial coinfection. If a test for a respiratory virus test is positive in a patient hospitalized for CAP, no sufficiently differentiating features exclude bacterial coinfection, thereby supporting the recommendation that empiric antibiotics be administered to all patients who are sufficiently ill to require hospitalization for CAP.
Randomized Controlled Trials (RCTs) assessing adjuvant corticosteroids for hospitalized Community-Acquired Pneumonia (CAP) show mixed results, suggesting Heterogeneity of Treatment Effect (HTE). Current guidelines conflict: some restrict use to septic shock, while others advocate for broader application in severe CAP. Among three recent, large RCTs focused on severe CAP, however, only one demonstrated significant benefit, raising the question: should severity-based treatment guidance really be preferred?. The debate surrounding corticosteroid use in CAP is complicated by two issues: the lack of a unified definition for ‘severe CAP’, with definitions either based on the American Thoracic Society criteria or severity scores like the Pneumonia Severity Index, and the reliance on Aggregate Data Meta-Analyses (ADMAs). ADMAs synthesize trial results by categorizing entire RCTs as severe or non-severe, while most RCT populations included patients with varying disease severities. Individual Patient Data Meta-Analyses (IPDMAs) enable stratification on a patient-level. Our recent IPDMA utilized multivariate predictive HTE modelling in six RCT datasets to identify patient characteristics predicting corticosteroid benefit, which suggested C-reactive protein (CRP) as a predictor of benefit. Therefore, this finding was externally validated in two other RCTs, revealing statistically significant HTE found across baseline CRP subgroups (i.e., ≤ 204 mg/L vs. >204 mg/L), while no such HTE was found across severity-based subgroups. These findings may advocate for corticosteroid treatment guided by CRP instead of disease severity. CRP, however, is unlikely the sole driver of corticosteroids benefit, as other potential sources of HTE like imaging or cytokines (‘known unknowns’) or other unmeasured variables (‘ unknown unknowns’) may exist, and moreover, our IPDMA post-hoc suggested HTE across aetiology and treatment timing. Moving forward, the efficacy of precision medicine in CAP hinges on rigorous replication of HTE findings —being notoriously susceptible to false positives— in independent datasets, and harmonized and standardized data collection in future trials. Based on current evidence, CRP may serve as a pragmatic tool to guide corticosteroid treatment, but given to the drug’s “pendulum swings” from broad use to avoidance over the last decades, caution remains essential.