Community-Acquired Pneumonia

BackgroundAdjunctive glucocorticoids may reduce mortality among patients with severe community-acquired pneumonia (CAP) in well-resourced settings. Whether these drugs are beneficial in low-resource settings with limited diagnostic and treatment facilities is unclear.MethodsIn this pragmatic, open-label, randomized, controlled trial conducted in 18 public hospitals in Kenya, we assigned adult patients who had received a diagnosis of CAP and who did not have a clear indication for glucocorticoids to receive either standard care for CAP or oral low-dose glucocorticoids for 10 days in addition to standard care. The primary outcome was death from any cause at 30 days after enrollment.ResultsA total of 2180 patients underwent randomization (1089 assigned to the glucocorticoid group and 1091 to the standard-care group). The median age of the patients was 53 years (interquartile range, 38 to 72); 46% were women. At day 30, deaths were reported in 530 patients (24.3%): 246 patients (22.6%) in the glucocorticoid group and 284 patients (26.0%) in the standard-care group (hazard ratio, 0.84; 95% confidence interval, 0.73 to 0.97; P = 0.02). The frequencies of adverse events and serious adverse events were similar in the two trial groups. Serious adverse events that were considered to be related to glucocorticoid administration occurred in 5 patients (0.5%).ConclusionsIn patients with CAP in a low-resource setting, adjunctive glucocorticoid therapy was associated with a lower risk of death than standard care. (Funded by Wellcome Trust and others; SONIA PACTR number, PACTR202111481740832; ISRCTN number, ISRCTN36138594.).

An observational, single-center study was conducted among hospitalized children with community-acquired pneumonia in the Baoding area. The objective was to compare the respiratory pathogen profiles and epidemiological patterns during and after the lifting of non-pharmaceutical interventions (NPIs, including mask-wearing, social distancing, lockdowns, etc.). A total of 9,362 hospitalized children diagnosed with CAP in Baoding from January 2022 to December 2023 were included. Both viral and bacterial pathogens were detected by multiplex PCR. The NPIs were lifted in Baoding from 2 December 2022. A comparative analysis was conducted on demographic data, epidemiological data, pathogen detection rates, and co-infection patterns that were compared between the full year 2022 and 2023. The detection rate of at least one pathogen significantly increased from 74.2% (2,925/3,940) in 2022 to 86.5% (4,690/5,422) in 2023 (P Mycoplasma pneumoniae, Streptococcus pneumoniae, human rhinovirus, respiratory syncytial virus (RSV), and Haemophilus influenzae were the predominant pathogens. Notably, co-infection rates rose from 25.1% (988/3,940) in 2022 to 45.1% (2,445/5,422) in 2023 (P < 0.001), particularly viral-bacterial co-infections. The positive detection rates for many pathogens among severe pneumonia cases increased. Additionally, an age shift in infection patterns was observed, with older children showing a higher prevalence of RSV. Following the lifting of NPIs, an increase in the detection rates of pathogens was observed, as were fluctuations in the dynamics of viral and bacterial pathogens, underscoring the urgent need to adapt clinical management and public health policies to address emerging infection trends. IMPORTANCE Community-acquired pneumonia (CAP) remains the leading infectious cause of death in children worldwide. Understanding the pathogens responsible for CAP is essential for effective diagnosis and treatment. This study examines the changes in respiratory pathogens and epidemiological patterns in children with CAP in Baoding, China, before and after the lifting of non-pharmaceutical interventions (NPIs). Data from 9,362 children diagnosed with CAP from January 2022 to December 2023 were analyzed. The detection rate of at least one pathogen increased significantly from 74.2% in 2022 to 86.5% in 2023. Notably, co-infection rates rose from 25.1% to 45.1%, with viral-bacterial co-infections being more common. This research underscores the urgent need to adapt clinical management and public health policies to address the changing infection trends, highlighting their importance and innovation in understanding the impact of NPIs on pediatric respiratory infections.

BACKGROUND: Endothelial glycocalyx degradation has been implicated in the pathogenesis of sepsis. Previous studies linked elevated plasma syndecan-1, an established biomarker of glycocalyx disruption, to mortality in sepsis. We aimed to determine the association of plasma syndecan-1 levels with clinical outcomes and host response changes in patients with community-acquired pneumonia (CAP) with various disease severities. METHODS: We included CAP patients upon presentation in three care settings: emergency department (ED), general ward, and intensive care unit (ICU). We stratified patients in a Normal-Syndecan-1 and an Elevated-Syndecan-1 group based on syndecan-1 levels measured in outpatient controls without infection, and measured 32 biomarkers reflective of five pathophysiological domains involved in sepsis immunopathology: coagulation activation, endothelial cell activation and dysfunction, cytokines, neutrophil degranulation, systemic inflammation and organ damage. We analyzed blood transcriptomes to obtain insight in changes in host response pathways in circulating leukocytes related with glycocalyx disruption. RESULTS: We included 50 non-infectious control patients and 384 CAP patients, with samples collected from 95 in the ED, 124 after admission to the general ward, and 165 after admission to the ICU. The Elevated-Syndecan-1 group showed significantly reduced 30-day survival compared to the Normal-Syndecan-1 group (log-rank p < 0.05). The relationship between syndecan-1 (continuous variable) and 30-day mortality was non-linear and independent of comorbidities and disease severity. Most biomarkers were already strongly elevated in the Normal-Syndecan-1 group relative to non-infectious controls, spanning all pathophysiological domains. All biomarkers showed further increases in the Elevated-Syndecan-1 group relative to non-infectious controls, which was also reflected in direct comparisons between the Normal-Syndecan-1 and Elevated-Syndecan-1 groups. Gene set enrichment analysis of blood leukocytes indicated a link between elevated syndecan-1 and increased expression of genes involved in extracellular matrix organization and hemostasis. CONCLUSIONS: Glycocalyx degradation, as measured by plasma syndecan-1, shows a non-linear association with mortality in patients with CAP. Key systemic host response changes implicated in sepsis pathogenesis occur prior to detectable glycocalyx degradation in this population.