Abstract Background Pneumococcal disease (PD) is a leading cause of morbidity among US children, particularly those with chronic medical conditions (CMC) and immunocompromising conditions (IC), and the decline in PD incidence was less pronounced in the late pneumococcal conjugate vaccine (PCV) 13 period. This study quantified healthcare resource utilization (HCRU) and costs among commercially and Medicaid-insured children with PD. Methods This retrospective observational cohort study used Merative™ MarketScan® Commercial Database and Multi-State Medicaid Databases to identify children with invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) episodes using inpatient and outpatient claims. HCRU and costs per PD episode were assessed in the commercially and Medicaid-insured populations, stratified by age (<2, 2-4, and 5-17 years) and risk group (CMC, IC, and no CMC/IC). Results Between 2018 and 2023, commercially insured children contributed 23.6 million person-years (PY) and Medicaid-insured children contributed 23.4 million PY; 423 and 664 children had IPD, 309,540 and 281,569 had ACP, and 2,721,354 and 2,596,201 had AOM in the commercial and Medicaid populations, respectively. In both databases, HCRU and cost was higher in children with CMC or IC, compared to no CMC/IC across age groups for all PD manifestations. For IPD and ACP, inpatient admissions were 1.4 to 2.2-fold longer for children with CMC or IC. For IPD, costs per episode were 2-to-3-fold higher in children with CMC or IC, compared with those without CMC/IC (Commercial: $76,278 and $72,130 vs. $22,371; Medicaid: $17,389 and $19,945 vs. $6,476, respectively). For ACP, costs were highest in children with IC, followed by CMC and no CMC/IC (Commercial: $7,343, $2,637, and $809; Medicaid: $3,257, $1,160, and $356, respectively). AOM showed a similar pattern, with highest costs in children with IC (Commercial: $608; Medicaid: $178), followed by CMC ($442; $141), and lowest in those without CMC/IC ($368; $123). Conclusions US children with underlying conditions that increase susceptibility to PD experience substantially higher HCRU and costs compared with those without such conditions, across all PD manifestations, regardless of insurance type and age group. These findings underscore the need for risk-based prevention strategies, including vaccination, beyond early childhood in high-risk pediatric populations.
Streptococcus pneumoniae is a leading cause of community-acquired pneumonia (CAP) in adults, yet microbiological diagnosis remains challenging. Quantitative lytA-PCR on nasopharyngeal samples has improved diagnostic yield; however, a substantial proportion of patients with confirmed pneumococcal pneumonia (PPn) remain lytA-negative. We hypothesized that nasopharyngeal microbiota profiles differ according to lytA-PCR status on nasopharynx and may reflect distinct pathogenetic pathways. We conducted a prospective, observational study including adults hospitalized with confirmed PPn. Nasopharyngeal samples were collected before initiation of antimicrobial therapy for lytA-PCR quantification and 16S rRNA gene sequencing. Patients were stratified according to nasopharyngeal lytA-PCR status. Microbiota diversity and composition were analysed at the genus and amplicon sequence variant (ASV) levels. Differential abundance was assessed using ALDEx2, and associations between pneumococcal load and Streptococcus ASVs were explored. Among 38 patients, 24 (63
The main burden of non-invasive pneumococcal diseases in adults is largely due to community-acquired pneumonia (CAP). This study aimed to investigate the distribution and dynamics of pneumococcal vaccine serotypes and to determine the proportion of CAP cases attributable to serotypes covered by 13-valent conjugate vaccine (PCV13), the 20-valent conjugate vaccine (PCV20), and the 23-valent polysaccharide vaccine (PPV23) among adults in Germany from 2020 to 2023. In this prospective multicenter cohort study, we analyzed all adult patients with CAP enrolled between January 1, 2020, and December 31, 2023, at 26 centers in Germany who provided urine samples for serotype-specific urine antigen detection (SSUAD) testing. Annual trends of pneumococcal vaccine serotypes from 2020 to 2023 were calculated for all patients and patient groups at risk using cluster-robust generalized linear models with heteroscedasticity-consistent standard errors. Of the 2,028 patients with all-cause CAP, 1,504 (1,008 patients aged ≥ 60 years, 373 younger patients with at least one comorbidity) had urine samples analyzed with SSUAD tests. Overall proportion of vaccine-type pneumococcal pneumonia among all-cause CAP for PCV13, PCV20, and PPV23 serotypes was 5.41
CURB-65 score usefulness has been assessed in COVID-19 pneumonia, but not in cohorts including immunocompromised patients. SARS-CoV-2 RNAemia is associated with mortality and unfavorable clinical outcomes in COVID-19. This study aimed to develop the VIRA score (Viremia-Integrated Risk Assessment), incorporating CURB-65 and RNAemia, for predicting 30-day COVID-19 pneumonia mortality. We included two multicenter cohorts of COVID-19 pneumonia: 539 immunocompetent and 280 immunocompromised patients, vaccinated against SARS-CoV-2 in 191 (35.4
It has been reported that the introduction of thirteen-valent pneumococcal conjugate vaccine (PCV13) had an influence on antibiotic resistance rates of invasive pneumococcal disease (IPD). Recent data about antibiotic resistance in IPD are scarce. The aim of the current study was to analyse the impact of PCV13 introduction and COVID-19 pandemic on antibiotic resistance in IPD and the effects of antibiotic resistance on mortality. Furthermore, we correlate vaccine and non-vaccine serotypes with antibiotic resistance. We included 8747 IPD cases from a Swiss nationwide IPD surveillance database for 2012–2022. Regression analyses were performed to examine significant trends over time and to identify serotypes and patient characteristics associated with antibiotic resistance. The proportion of non-susceptibility to erythromycin (IRR: 0.9, p < 0.001) and cotrimoxazole (IRR: 0.9, p < 0.001) decreased from 2012 to 2022. Penicillin non-susceptibility remained constant with a dip in 2022 (2012: 9.2
Abstract Adjunctive corticosteroids are increasingly used in Severe Community-Acquired Pneumonia (sCAP) requiring admission to the intensive care unit (ICU), based on evidence derived largely from immunocompetent populations. Immunocompromised hosts, however, represent a distinct and growing subgroup among critically ill patients with sCAP, characterised by baseline immune defects, broader pathogen spectra, and a heightened susceptibility to treatment-related harm. Whether corticosteroid strategies validated in the general population can be safely and effectively extrapolated to immunocompromised ICU patients with sCAP remains uncertain, despite their growing use in contemporary ICU practice. Immunocompromised patients admitted to the ICU with sCAP experience compounded alterations in host defence, driven by pre-existing immune dysfunction and superimposed critical illness–associated immune dysregulation. In this setting, corticosteroids may attenuate inflammation-mediated lung injury, but may also deepen immune suppression, distort clinical evolution, and increase susceptibility to opportunistic superinfections and pathogen reactivation. Randomised trials and meta-analyses supporting corticosteroid use in sCAP have systematically excluded immunocompromised patients, treating immunosuppression as an exclusion criterion rather than a stratification variable, and commonly rely on short-term endpoints that fail to capture delayed infectious complications relevant to this population. Available observational data and pathogen-specific evidence suggest substantial heterogeneity of treatment effect (HTE) across immunocompromised subgroups, influenced by immune substrate, pathogen context, and cumulative immunosuppressive burden. Among the pathogen-specific contexts in which corticosteroids have the strongest evidence, Pneumocystis jirovecii pneumonia (PJP) stands out as the principal indication: adjunctive corticosteroids have demonstrated clear mortality benefit in AIDS-associated severe PJP, though this benefit does not extend uniformly to HIV-negative immunocompromised patients with PJP. Consequently, standard corticosteroid treatment in all CAP subgroups is unlikely to be appropriate. In immunocompromised ICU patients with sCAP, corticosteroid therapy should neither be routinely applied nor categorically avoided. Instead, decisions should be individualised, guided by a clearly defined therapeutic target, careful assessment of immune status, and consideration of the risk for opportunistic infections. When used, corticosteroids should be administered at the lowest effective dose and for the shortest feasible duration. Dedicated studies incorporating immune stratification, pathogen-informed approaches, and outcomes relevant to delayed infections are urgently needed. Until such evidence is available, careful risk-balance assessments to decide steroids in these patients.
Community-acquired pneumonia (CAP) is a leading cause of morbidity in adults with chronic conditions. Although pneumococcal vaccine effectiveness (VE) has been demonstrated in older adults, evidence is scant regarding adults < 65 years. We evaluated pneumococcal VE against CAP-related hospitalization in at-risk adults aged 18–64 years. We conducted a multicentre case-control study in Spain (2020–2024). Cases were adults aged 18–64 years with risk conditions, hospitalized for ≥ 24 h, with radiological and clinical patterns compatible with CAP. Controls were hospitalized patients with risk conditions but without pneumonia. Vaccination status was classified as 23-valent pneumococcal polysaccharide vaccine only, pneumococcal conjugate vaccine only, sequential vaccination, or unvaccinated. Logistic regression was used to estimate crude and adjusted odds ratio (OR) values, with VE calculated as (1–OR) × 100. Analyses were stratified by immune status, and a sensitivity analysis was performed excluding SARS-CoV-2 cases. We included 805 cases and 806 controls. None of the pneumococcal vaccination strategies showed significant effectiveness against hospitalization for CAP. In immunocompromised individuals, 23-valent pneumococcal polysaccharide vaccine showed significantly negative adjusted VE (-142.0, 95
Abstract Acute respiratory distress syndrome (ARDS) remains a high‑mortality condition despite major advances in ventilatory and supportive care. Because lung injury is driven by uncontrolled inflammation and disruption of the alveolar–capillary barrier, corticosteroids have long been considered a biologically plausible therapy. Over several decades, randomized trials have evaluated different corticosteroid types, doses, durations, and initiation timings in heterogeneous populations, including patients with primary ARDS and those with sepsis or pneumonia complicated by ARDS. The COVID‑19 pandemic provided a unique opportunity to study a more homogeneous cause of ARDS, generating additional evidence supporting corticosteroid efficacy in virus‑related respiratory failure. Despite these advances, clinical practice remains variable worldwide. Evolving definitions, diverse trial designs, and etiologic variability have led to uncertainty regarding indication, optimal dosing, drug selection, and treatment duration. The new global definition of ARDS now includes patients supported with noninvasive ventilation or high‑flow nasal oxygen, raising questions about how evidence derived from invasively ventilated populations applies to these groups. Parallel research identifying inflammatory subphenotypes with potentially divergent treatment responses further underscores the need for individualized, evidence‑based strategies. In this review, we examine conceptual, biological, and clinical considerations and synthesize the available evidence to inform decision‑making. We propose a pragmatic, context‑based framework to guide corticosteroid use in ARDS according to etiology and patient characteristics, emphasizing early initiation—ideally within 24–48 hours—and regimens equivalent to ≥80 mg/day of methylprednisolone or ≥400 mg/day of hydrocortisone for at least seven days, which have demonstrated efficacy with an acceptable safety profile. Research priorities include optimizing dose and duration, evaluating non‑ventilated and underrepresented subgroups, and clarifying phenotype‑specific effects and long‑term safety.
Abstract 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.
Abstract 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.
Abstract Background There are significant racial and environmental disparities in the burden of pneumococcal disease. Understanding the role of social determinants of health (SDoH) on pneumococcal disease can help health authorities identify health inequities and develop interventions to reduce these disparities. This targeted literature review (TLR) aimed to examine the clinical and economic burden of pneumococcal disease in US adults with a focus on SDoH such as race, urbanicity, and socioeconomic status. Methods A TLR of studies published between January 2012 and July 2024 was conducted using PubMed (via Medline) and Centers for Disease Control and Prevention (CDC) surveillance data. Supplementary searches were made on Google Scholar to address data gaps. Outcomes of interest were incidence, prevalence, mortality, healthcare resource use, costs, and vaccine coverage rates by race/ethnicity, urbanicity (population density), and socioeconomic variables (income, education, employment status and home ownership). Results Of 4,609 identified publications, 12 studies were included. Black adults had the highest incidence and mortality rates and longest hospital stay due to pneumococcal disease across all adult age groups. Additionally, Black (compared to non-Black) adults were more likely to be hospitalized at younger ages (50–64 years). Black adults ≥50 years incurred significantly higher pneumococcal disease hospitalization costs compared to non-Black adults. Lower urbanicity displayed higher mortality rates for adults with pneumonia. Adult patients 18–64 years living in more disadvantaged areas had a higher risk of hospitalization for IPD. Similarly, adults living in higher levels of area-based poverty had increased rates of CAP hospitalizations. Incidence of community-acquired pneumonia (CAP) was higher in early retirees and their adult dependents compared to their employed counterparts and adult dependents. Vaccination rates were lower in Black adults, rural residents, those with lower SES, education or income, blue-collar workers, and those who did not own a home. Conclusion Disparities in pneumococcal disease burden and vaccination uptake exist among US adults, particularly among Black adults, rural residents and those with lower education and income. There is paucity of studies examining disparities in pneumococcal disease and inequities according to race, urbanicity, and socioeconomic status warranting further investigation of the topic to inform prevention strategies.
Abstract 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.
Eosinopenia has been reported as a marker of severity in infections, but its prognostic value in patients with severe community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) is unclear. We retrospectively analyzed 496 patients with severe CAP admitted to the ICU and stratified them according to the presence of eosinopenia on admission. We compared clinical characteristics, laboratory data, microbiological etiology, treatment, complications, and outcomes between groups. Independent factors associated with 30-day mortality were identified using multivariable Cox regression. Discriminative performance of eosinophil count, severity scores (CRB-65, CURB-65, PSI), and a modified CURB-65 incorporating eosinopenia (CURB-65Eos) were assessed using ROC curves. Eosinopenia was present in 163/496 patients (33
Corticosteroids have long been used as immunomodulatory agents in viral respiratory infections, but their role in influenza and COVID-19 remains controversial. While both diseases share overlapping pathogenic mechanisms involving hyperinflammation and immune dysregulation, clinical evidence suggests divergent outcomes in response to corticosteroid therapy. This review critically examines the evidence regarding corticosteroid use in influenza and COVID-19, focusing on their impact on mortality, disease progression, and secondary infections. A narrative review was conducted including randomized controlled trials, meta-analyses, and major observational studies published between 2000 and 2025. Data were analyzed comparatively for influenza (seasonal and pandemic strains) and SARS-CoV-2 infection. In influenza, most studies associate corticosteroid administration—particularly at high doses or prolonged courses—with increased mortality, delayed viral clearance, and higher rates of secondary bacterial pneumonia. Conversely, in COVID-19, randomized trials such as RECOVERY demonstrated that low-to-moderate doses of dexamethasone significantly reduce mortality in patients requiring oxygen or mechanical ventilation, without clear benefit in mild disease. These opposing outcomes highlight the importance of timing, dosing, and patient selection, reflecting distinct immunopathological trajectories between the two infections. Corticosteroid therapy exerts context-dependent effects in viral pneumonia. While detrimental in most cases of influenza, it is beneficial in severe COVID-19 when guided by systemic inflammation. Future strategies should focus on personalized and real-time immune monitoring to tailor immunomodulatory interventions to each patient’s inflammatory and virological status.
Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Although corticosteroids have been proposed as immunomodulatory, controversies surrounding the results of clinical trials have limited their widespread use. This review aims to determine which biomarker-guided corticosteroid treatment for CAP is generally agreed upon in the latest published studies and to discuss the main aspects to be taken into consideration based on lessons learnt from patients with conditions such as influenza, SARS-CoV-2 infection or the recently identified subphenotypes in acute respiratory distress syndrome (ARDS). Most studies have demonstrated that high C-reactive protein concentrations at the time of admission are associated with a hyperinflammatory state and that patients are more likely to benefit from corticosteroid treatment if they have high concentrations. High levels of C-reactive protein (CRP) were used as an inclusion criterion in one clinical trial, demonstrating that treatment failure was reduced in the corticosteroid group. A post-hoc analysis of the results of several studies also showed that CRP levels above 200 mg/L were associated with benefits in patients receiving corticosteroids. Recent guidelines have proposed the use of corticosteroids in patients with severe CAP or septic shock. Corticosteroids could be more beneficial for patients with a hyperinflammatory subphenotype; however, there are currently no prospective studies evaluating this approach. Further studies are needed to clarify the role of biomarkers in personalised medicine for patients with CAP. In the meantime, patients with severe CAP or high CRP levels should be treated with corticosteroids.
In most patients with CAP, corticosteroids should be avoided due to complications such as immunosuppression and hyperglycaemia. Studies of hydrocortisone have shown corticosteroids might be of benefit in patients with severe CAP and high inflammation measured by CRP. Differences in results between trials of corticosteroid therapy suggest heterogenicity in study populations and the need for future studies in standardized populations. Scientific evidence shows corticosteroid use can reduce short-term mortality and the need for mechanical ventilation in hospitalized patients with severe CAP. However, this approach should not be generalized to all patients with CAP. Use should be guided by biomarkers such as CRP to identify patients who will benefit the most. Corticosteroids should not be routinelly used in viral pneumonia, with the exception of hypoxemic SARS-CoV-2 pneumonia, in which their benefit is well established.
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. 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). 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. 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.
The diagnostic performance of the BioFire® FilmArray® Pneumonia Panel Plus (FAPP) compared to standard microbial culture (SMC) during bronchiectasis (BE) exacerbations is unknown. To compare the microbiological diagnostic performance between FAPP and SMC during BE exacerbations. A prospective observational study was conducted in adults with a BE exacerbation at the Hospital Clinic of Barcelona (Spain) June 2020 to April 2022. All sputum samples underwent processing using both the FAPP and SMC (n = 109) but we focused in good quality samples (n = 73). The FAPP detected pathogens in a higher percentage (n = 64, 88
Invasive pulmonary aspergillosis (IPA) is a life-threatening fungal infection traditionally associated with severely immunocompromised hosts, particularly those with hematologic malignancies. However, its epidemiological profile has shifted in recent years, with a rising incidence among critically ill patients in intensive care units (ICUs), many of whom lack classical risk factors. This change is driven by increased use of corticosteroids and immunomodulatory therapies, the growing prevalence of chronic lung disease, and severe viral pneumonias such as influenza and COVID-19. In these patients, airway epithelial injury, immune dysregulation, and mechanical ventilation facilitate fungal invasion even in the absence of profound immunosuppression. Corticosteroids play a central role in IPA pathogenesis. While they limit hyperinflammation, they simultaneously impair fungal clearance by suppressing NF-κB signaling, downregulating TNF-α production, and promoting IL-10 secretion, resulting in a Th2-skewed immune profile. Neutrophil recruitment persists but becomes dysregulated, contributing to tissue injury rather than effective pathogen elimination. Corticosteroids may also directly enhance Aspergillus growth, further compounding risk. Diagnosis of IPA in ICU patients remain challenging because radiological hallmarks such as the halo sign are uncommon, and distinguishing colonization from invasive disease is difficult. Serum and bronchoalveolar lavage galactomannan, β-D-glucan assays, and PCR can improve early detection, but no single test is definitive in this heterogeneous population. As much as possible, high-quality lower respiratory tract samples should be obtained. Furthermore, effective treatment requires not only timely diagnosis, but also careful selection of antifungal taking into consideration pharmacologic challenges of ICU patients and pharmacodynamics of antifungals. Recognition of high-risk patients such as those receiving corticosteroids, those with chronic lung disease, severe viral pneumonia, or requiring invasive ventilation is critical to improve outcomes. Mortality in this group can exceed that of neutropenic patients, underscoring the need for heightened clinical suspicion and timely antifungal therapy. A deeper understanding of the immunopathogenesis of IPA in non-neutropenic patients, particularly the dual effects of corticosteroids on inflammation and host defense, may inform risk stratification and guide earlier intervention. Enhanced surveillance, prompt diagnostic workup, and judicious use of immunomodulatory therapy represent key strategies to mitigate the rising burden of this devastating infection in ICU settings.
The incidence of pneumococcal disease differs based on demographic and clinical factors, yet the impact of area-level social determinants of health, particularly for children, remains less understood. We characterized the relationship between individual and area-level social vulnerability and incidence of all-cause pneumonia (ACP), acute otitis media (AOM), and invasive pneumococcal disease (IPD) among children across the US. Using a retrospective observational design, we measured disease incidence among children 18 years and younger covered by Medicaid, using claims from 2017 through 2019. We measured social vulnerability using quintiles of the county-level Minority Health Social Vulnerability Index (MHSVI) and its six subthemes (Socioeconomic Status; Household Composition and Disability; Minority Status and Language; Housing Type and Transportation; Health Care Infrastructure and Access; Medical Vulnerability). After calculating county-level ACP, AOM, and IPD incidence rates overall and among counties in each MHSVI quintile, we used Poisson regression to characterize the relationship between social vulnerability and disease incidence, controlling for confounding by child demographic characteristics. We analyzed this relationship overall and within age and race/ethnicity subgroups. Across 38.1 million children, ACP, AOM, and IPD incidence rates were 1,767, 16,486, and 3.3 per 100,000 person-years, respectively. ACP and AOM incidence rates were lower among children in the most versus least socially vulnerable counties (unadjusted incidence rate ratio = 0.89 and 0.75, respectively; both P < 0.0001); differences were attenuated but remained statistically significant after adjusting for child demographics. The direction of the relationship between ACP and AOM incidence and vulnerability varied by type of vulnerability: incidence was lower in counties that were most (versus least) vulnerable based on Minority Status and Language or Housing Type and Transportation, but higher in those most vulnerable based on Household Characteristics or Disability and Medical Vulnerability. Differences in IPD incidence between the most versus least vulnerable counties were generally non-significant, due to the low overall incidence. Incidence of AOM and ACP in children varies significantly by demographic characteristics and county-level medical and non-medical social determinants of health. Social vulnerability may be useful to identify factors associated with disparities in pneumococcal disease and develop targeted interventions to reduce them.
