Infants who are HIV-exposed uninfected (HEU) are at greater risk of death compared with infants who are HIV-unexposed, particularly in the first 6 months of life. We investigated the causes of death (CoD) of HEU and HIV-unexposed infants using postmortem minimally invasive tissue sampling. This prospective, observational study enrolled decedents less than 6 months of age at a secondary-tertiary level care hospital in Soweto, South Africa. The minimally invasive tissue sampling included needle core-biopsy sampling for histopathology of brain, lung and liver tissue. Microbiologic culture and/or molecular tests were performed on lungs, liver, blood and cerebrospinal fluid. Underlying, immediate and antecedent CoD were determined by a multidisciplinary team of medical experts. The median age (9 [interquartile range 3, 30] vs. 8 [interquartile range 3, 22] days) and sex distribution (female 58.5% vs. 47.9%) were similar between HEU (n = 65) and HIV-unexposed (n = 119) decedents. A larger proportion of HEU decedents (60%, 39/65) compared with HIV-unexposed decedents (44.5%, 53/119; P = 0.045) had preterm birth as an underlying CoD. Among HEU infants compared with HIV-unexposed infants, sepsis was attributed as an immediate or antecedent cause of death in 46.2% (30/65) versus 36.1% (43/119), respectively. Of the 30 HEU infants with sepsis, 76.7% (23/30) were classified as presumed hospital acquired, most commonly associated with Acinetobacter baumannii (56.5% [13/23]) and Klebsiella pneumoniae (13.0% [3/23]). Similarly, among HIV-unexposed infants with sepsis (n = 43), 72.3% (31/43) were classified as presumed hospital acquired, with A. baumannii (38.9% [12/31]) and K. pneumoniae (38.9% [12/31]) as the predominant pathogens. Pneumonia was attributed as an immediate or antecedent cause of death in 32.3% (21/65) of HEU and 36.1% (43/119) of HIV-unexposed infants. Among those with pneumonia, presumed hospital-acquired pneumonia was identified in 47.6% (10/21) of HEU and 72.1% (31/43) of HIV-unexposed infants (P = 0.035), most frequently due to A. baumannii (50.0% [5/10] HEU; 41.9% [13/31] HIV-unexposed) and K. pneumoniae (30.0% [3/10] HEU; 19.4% [6/31] HIV-unexposed). Presumed community-acquired pneumonia was identified in 52.4% (11/21) of HEU and 27.9% (12/43) of HIV-unexposed infants (P = 0.035). The predominant community-acquired pathogens were respiratory syncytial virus (36.4% [4/11] HEU; 25.0% [3/12] HIV-unexposed) and K. pneumoniae (36.4% [4/11] HEU; 8.3% [1/12] HIV-unexposed). Our study highlights preterm birth as an important underlying CoD among HEU and HIV-unexposed decedents. There was a larger proportion of presumed community-acquired pneumonia deaths in HEU compared with HIV-unexposed decedents. Further research is warranted to explore these differences and develop effective preventive strategies.

Excessive antibiotic use promotes resistance and side effects and increases healthcare costs. Antibiotics are often prescribed to treat community-acquired pneumonia (CAP). The optimal duration of treatment is debated. In this study, we compare the efficacy of shorter and longer antibiotic treatment for CAP in the outpatient setting and evaluate the pertinent economic, environmental, ethical, and societal issues. Relevant articles published up until 5 February 2024 were identified by searches in the electronic databases MEDLINE, Embase, and CENTRAL as well as in trial registries and in reference lists of systematic reviews, including health technology assessment (HTA) reports. All randomized controlled trials (RCTs) comparing short- and long-term antibiotic treatment in children with outpatient CAP were included in the benefit assessment. A 10% difference was set as the non-inferiority margin. Seven RCTs that studied a total of 8590 children were included. In young children with clinically diagnosed CAP, a three-day course of amoxicillin was non-inferior to 5-, 7-, or 10-day courses with respect to treatment success (relative risk [RR] 0.99; 95% confidence interval [0.96; 1.02]). Shorter treatment was associated with fewer (non-severe) adverse events (0.87, [0.78; 0.96]). Relapses and deaths were rare overall. Where shorter treatment was equally effective, it also had economic and ecological benefits. Three days of antibiotic treatment with amoxicillin may be just as effective as longer treatment, and also better tolerated, in younger children with clinically diagnosed, outpatient, non-severe CAP, and would conserve resources. These findings can be taken into account in the formulation of guideline recommendations.

Aim: Community-acquired bacterial pneumonia (CABP) remains a major cause of morbidity and mortality worldwide, particularly among elderly and susceptible populations. Escalating antimicrobial resistance among prevalent CABP pathogens in China, combined with safety limitations of existing regimens, underscores the urgent need for novel therapeutic strategies. Lefamulin (LEF) and omadacycline (OMA), recently approved in mainland China, offer promising alternatives, but direct comparative evidence is lacking. This study aims to indirectly compare the clinical efficacy and safety outcomes of LEF versus OMA in the treatment of CABP and to explore subgroup differences in high-risk populations. Materials & methods: A systematic literature review was conducted across PubMed, Embase, the Cochrane Library and ClinicalTrials.gov from inception through March 2024, limited to English-language studies, to identify phase III randomized controlled trials evaluating LEF or OMA in adults with CABP. The Bucher method was used for the indirect comparison, with effect estimates reported as risk ratios (RRs) and 95% CIs. Similarities in trial design and populations supported the transitivity assumption. Primary end points were early clinical response (ECR), investigator-assessed clinical response (IACR) at test of cure (TOC) and treatment-emergent adverse events leading to death. Subgroup analyses were further stratified by patient age (elderly patients), presence of comorbidities and causative pathogens. Results: Three randomized controlled trials involving 2063 patients were included in this study. LEF and OMA demonstrated comparable efficacy in terms of ECR (RR: 1.01, 95% CI: 0.93-1.09) and in terms of IACR at TOC (RR: 0.95, 95% CI: 0.88-1.02). The relative risk of treatment-emergent adverse events leading to death in the LEF group compared with the OMA group was 0.67 (95% CI: 0.15-3.02), with no statistically significant difference observed. In subgroup analysis, LEF demonstrated statistically significant superiority over OMA in treating patients with Haemophilus influenzae infections (RR: 1.28, 95% CI: 1.03-1.60). No other subgroups reached statistical significance. LEF showed a numerical trend toward favoring in multiple subgroups, including the elderly, patients with comorbidities, and those infected with specific pathogens, particularly in the ECR analysis. Meanwhile, OMA demonstrated potential numerical advantages in a few subgroups defined by comorbidities or specific pathogens for IACR at TOC. Conclusions: Both LEF and OMA have been shown to be effective and safe in treating CABP. LEF demonstrated significant benefit in Haemophilus influenzae infections and consistently favorable trends in high-risk or specific infected subgroups. OMA also shows favorable trends in certain patient groups. These findings highlight the need to further accumulate additional clinical data or real-world evidence to support future comparative research. The introduction of novel antibiotics, such as LEF and OMA, represents an important step toward addressing the pressing challenge of antimicrobial resistance and improving outcomes for patients with CABP in China.

Community-acquired pneumonia (CAP), particularly severe CAP (SCAP), poses a significant clinical challenge with high mortality. MicroRNAs, including miR-342-3p, have been implicated in various pulmonary diseases, suggesting a potential role in SCAP. To examine the expression, functional mechanisms, and clinical relevance of miR-342-3p in SCAP. Bioinformatic analysis was performed on two independent GEO datasets (GSE196399 and GSE136390). Serum miR-342-3p levels were measured in a clinical cohort of 109 SCAP patients and 109 healthy controls by RT-qPCR, and its correlation with clinical prognosis was analyzed. An in vitro pneumonia model was established using LPS-stimulated MRC-5 cells. Gain-of-function experiments of miR-342-3p were achieved through mimic transfection. MiR-342-3p's involvement in inflammation, cytotoxicity, and pyroptosis was assessed via ELISA, western blot, CCK-8, and LDH assays. The interaction between miR-342-3p and EP300 was confirmed by dual-luciferase reporter and RNA pull-down assays, and its functional role was confirmed through rescue experiments. The downregulation of miR-342-3p in SCAP patient serum correlated with increased mortality. In vitro, miR-342-3p overexpression reduced LPS-induced inflammation and pyroptosis. Bioinformatics analysis confirmed that histone acetyltransferase EP300 is a candidate target gene for miR-342-3p. Mechanistically, miR-342-3p directly targeted and negatively regulated EP300. Overexpression of EP300 abolished the anti-inflammatory and anti-pyroptotic effects of miR-342-3p through the activation of NF-κB p65. MiR-342-3p acts as a protective factor in SCAP by targeting EP300 to inhibit inflammation and pyroptosis. These results indicate the potential of miR-342-3p as a biomarker and therapeutic target in SCAP.

Respiratory illness is the most frequent reason for unnecessary antibiotic use among hospitalized adults. In randomized trials, procalcitonin and respiratory virus testing without guidance on test interpretation do not influence antibiotic decision-making. We conducted a pragmatic, randomized, controlled trial of antimicrobial stewardship-guided test interpretation versus usual care among hospitalized adults receiving antibiotics for suspected respiratory infection with either low procalcitonin or positive respiratory virus testing at 2 hospitals. The intervention involved a templated note in the electronic health record interpreting test results in terms of the post-test probability of bacterial pneumonia and antibiotic decision-making. When probability of bacterial pneumonia was low, discontinuation of antibiotic therapy was recommended. The primary outcome was in-hospital antibiotic days of therapy. Between 1 November 2023 and 10 January 2025, 107 adults were enrolled, including 65% with low procalcitonin, 30% with positive respiratory virus testing, and 5% with both. The intervention decreased antibiotic use by an average of 4.1 in-hospital days of therapy (7.5 versus 11.6, P = .006). All respiratory antibiotics were discontinued within 5 days of initiation for 76% of intervention patients versus 49% with usual care (P = .004). Length of stay (5.5 days intervention versus 6.6 days usual care, P = .16) and 30-day readmission (7% intervention versus 19% usual care, P = .079) did not significantly differ between groups. In this proof-of-concept study, antimicrobial stewardship-guided interpretation of laboratory tests for viral infection using a simple template safely decreased unnecessary antibiotic use for hospitalized adults with community-acquired respiratory illness. Clinical Trial Registration. NCT05976581.

Risk prediction models for community-acquired pneumonia (CAP) in hospitalised children are limited, especially in upper-middle-income countries. We developed a PaEdiatric Pneumonia Severity (PEPS) score to aid early risk stratification and examined its discriminatory ability. Prospective cohort study. Between April 2022 and April 2023, children aged 1 month to <12 years hospitalised with radiographic-confirmed CAP were enrolled in Sabah, Malaysia. Key clinical factors were collected to develop risk profiles for mild, moderate, and severe CAP. The PEPS score was derived from the final multivariable model and its ability to discriminate CAP severity assessed. Among 868 children, 639 (73.6%) had mild, 83 (9.6%) moderate, and 146 (16.8%) severe CAP. Independent factors associated with moderate/severe CAP were age <6 months (adjusted OR (ORadj)=6.81, 95% CI 4.65 to 9.98), partial/unvaccinated status (ORadj=2.66, 95% CI 1.47 to 4.81), vomiting/refusal of feeds (ORadj=1.77, 95% CI 1.19 to 2.61), hypoxaemia (oxygen saturation 90-93% (ORadj=2.38, 95% CI 1.22 to 4.64); <90% (ORadj=28.88, 95% CI 13.37 to 62.35)) and anaemia (ORadj=1.76, 95% CI 1.17 to 2.67). The model demonstrated excellent discrimination in identifying risk of children having moderate/severe CAP (c-statistic=0.81, 95% CI 0.78 to 0.84). The developed PEPS score (0-13) stratified children into low-risk (score 0-1), moderate-risk (score 2-4) and high-risk (score ≥5) groups with observed rates of moderate/severe CAP 10.9%, 29.1%, and 76.9%, respectively, and demonstrated strong predictive performance for moderate/severe CAP (c-statistic=0.81, 95% CI 0.77 to 0.84). The PEPS score, the first developed in an upper-middle-income country using radiographic-confirmed CAP, accurately discriminates mild from moderate/severe hospitalised CAP. It may support case management in similar settings, but requires external validation before broader implementation.

Community-acquired pneumonia (CAP) remains a significant global health challenge. This review summarizes the major advances in clinical research or CAP between October 1, 2024, and September 30, 2025. Given the high prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in China, PCR test for MRMP was recommended in pediatric patients to guide appropriate antibiotic selection. Increased attention is warranted for respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) due to their increasing prevalence and poor prognosis. PSI and CURB-65 scores remain the reliable tools for assessing the severity of CAP, while the SOFA-2 score may offer a promising approach for identifying patients requiring intensive care unit (ICU) admission. Although multiplex PCR (mPCR), targeted next-generation sequencing (tNGS), and metagenomic next-generation sequencing (mNGS) have been widely adopted in clinical practice, current evidence does not demonstrate sufficient benefits in improving patient survival or optimizing antibiotic stewardship. A rational, empirical antibiotic strategy should be individualized according to local pathogen epidemiology, risk of antimicrobial resistance and aspiration, and patient's clinical presentation. Short-course antibiotic therapy guided by "clinical stability" criteria is reliable, yet achieving stability requires more time in elderly patients and cases with comorbidities. Cefpirome and lefamulin are new antimicrobial agents on the market, but further clinical data are needed to support their use in severe cases and elderly patients. Suraxavir marboxil (GP681), a newly antiviral agent drug targeting the polymerase acidic protein of the influenza virus RNA polymerase, has recently been approved in China. Extending the administration of steroids to severe CAP without septic shock should be approached with extreme caution. High level of C-reactive protein may serve as a potential indicator for identifying cases who could benefit from steroids. In addition, RSV vaccines and monoclonal antibodies will emerge as important strategies for preventing RSV pneumonia in high-risk populations.

Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality, particularly in older adults and patients with chronic co-morbidities. Cytokine patterns and simple hematological indices may improve risk stratification beyond conventional clinical scores. In this prospective single-center study, 41 adults with CAP treated at Kaunas Hospital of Lithuanian University of Health Sciences between November 2024 and March 2025 were enrolled. Clinical data, pneumonia severity index (PSI), complete blood count-derived indices (neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], systemic immune-inflammation index [SII]), and serum concentrations of interleukin (IL)-6, IL-8, interferon (IFN)-γ, and G-CSF were obtained on admission (Visit 1) and after 7 days of treatment (Visit 2). Patients were stratified by age (≤65 vs >65 years), co-morbidities, and PSI class. Non-parametric tests and Spearman correlations were applied. The results indicate that patients with co-morbidities and those > 65 years had significantly higher IL-6 levels than younger and non-comorbid patients. IL-6, IFNγ, and G-CSF concentrations were highest at admission and declined by day 7, particularly in PSI Class II patients. Higher PSI classes were associated with increased IL-8, IL-6, and IFNγ. NLR and SII were significantly higher in older patients and in PSI III-IV compared with PSI I-II. IL-6 and G-CSF showed strong positive correlations with NLR and SII, especially in elderly and comorbid patients, whereas PLR displayed weaker and less consistent associations. From these data, it is concluded that in CAP, serum IL-6, IFNγ, and G-CSF reflect age, co-morbidity burden, and disease severity, while NLR and SII closely mirror cytokine-driven systemic inflammation. These readily available indices may serve as cost-effective prognostic markers and, combined with cytokine profiling, could enhance early risk stratification and guide individualized management in CAP.

Objective: To characterize the clinical, radiological, and epidemiological profile of patients hospitalized with community-acquired pneumonia (CAP), compare the characteristics of vaccinated and unvaccinated children and identify factors associated with prolonged hospitalization. Methods: A retrospective, monocentric cohort study was conducted at the Instituto de Puericultura e Pediatria Martagão Gesteira (IPPMG), a University Pediatric Hospital affiliated with the Universidade Federal do Rio de Janeiro (UFRJ), from January 2013 to December 2018. The study included children and adolescents aged 29 days to 14 years hospitalized with CAP. Data on demographics, clinical presentation, radiological findings, vaccination status, comorbidities, and hospitalization outcomes were analyzed. Bivariate and multivariate logistic regression analyses were performed to identify factors associated with prolonged hospitalization (&gt;10 days). Results: Among 185 patients analyzed, 58.9% were male and 89.7% were under 5 years of age. Comorbidities were present in 61.5% of patients, with neurological disorders being the most frequent (22.0%). 10-valent pneumococcal conjugate vaccine (PCV10) vaccination coverage was 75.6%. Vaccinated patients had significantly higher median age (22 vs. 15 months; P = .048) and daycare attendance (32.5% vs. 7.7%; P = .012), but lower occurrence of neurological disorders (17.8% vs. 33%; P = .041) and other comorbidities (13.6% vs. 30.8%; P = .014). Alveolar consolidation was the most common radiological finding, and pleural effusion was the most frequent complication (21.9%). The median hospitalization duration was 11 days. In the multivariate analysis, neurological disorders and pleural effusion were independent predictors of prolonged hospitalization (&gt;10 days). Conclusion: Despite high PCV10 vaccination coverage, severe CAP requiring hospitalization continues to occur, particularly in patients with underlying comorbidities. Neurological disorders and pleural effusion were significant predictors of prolonged hospitalization. Cite this article as: Santana BP, D’Elia C, Sant’Anna CC, Sant’Anna MFBP. Hospitalized children and adolescents with community-acquired pneumonia: clinical and epidemiological profile after the introduction of the 10-valent pneumococcal conjugate vaccine. Cerrahpaşa Med J 2026, 50, 0093, doi:10.5152/cjm.2026.25093.

Diagnosing invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD) remains challenging due to the non-specific nature of imaging findings, the limited sensitivity of current diagnostic methods, and the difficulty of obtaining appropriate clinical specimens. To evaluate the diagnostic accuracy of sputum galactomannan (GM) testing in COPD patients with IPA. In this multicenter cross-sectional study, COPD patients with suspected IPA and patients with community-acquired pneumonia (CAP) were enrolled. GM testing was performed on sputum, serum, and bronchoalveolar lavage fluid (BALF) samples, while fungal culture was conducted on sputum samples. Diagnostic performance was assessed using the EORTC/MSGERC criteria as the reference standard. A total of 134 patients were included, comprising the COPD + IPA group (n = 43), the COPD + CAP group (n = 70), and the CAP group (n = 21). The areas under the receiver operating characteristic curve (AUCs) for GM detection in sputum, BALF, and serum were 0.833 (95% CI: 0.753-0.913), 0.884 (95% CI: 0.799-0.970), and 0.659 (95% CI: 0.552-0.766), respectively. The optimal cut-off values for sputum and BALF GM were 1.64 and 1.12, respectively. At these thresholds, sputum GM demonstrated a sensitivity of 79.1% and specificity of 75.7%, while BALF GM showed a sensitivity of 76.5% and specificity of 96.6%. Sputum GM testing demonstrates significant diagnostic value for IPA in COPD patients and provides a non-invasive alternative with reliable performance, making it a promising tool for preliminary screening and reducing the need for invasive procedures in clinical practice. ChiCTR2400089800.

Dual-targeting ketolide-quinolone hybrids overcome erm-mediated resistant pathogens via ribosomal and DNA gyrase inhibition.

Inflammation plays a central role in atherosclerosis development and subsequent cardiovascular complications, including heart attack and stroke. Patients with inflammatory conditions such as community-acquired pneumonia (CAP) present with an elevated risk of cardiovascular events, which is likely driven by unresolved systemic inflammation. Targeting this heightened inflammatory burden may present a novel therapeutic strategy to attenuate heart attack risk in CAP survivors. Icosapent ethyl (IPE), an omega-3 fatty acid, demonstrates both pro-resolving and cardioprotective properties. The Targeting Vascular Inflammation In Patients with CAP (TIN-CAP) trial aims to evaluate the efficacy of IPE in mitigating vascular inflammation in CAP survivors. TIN-CAP is a multicentre, randomised, double-blind, placebo-controlled trial. Eligible adults diagnosed with CAP in hospital or the emergency department will complete baseline assessments within 14 days of diagnosis including 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT angiography, bloodwork and quality of life evaluation (EuroQol - 5 Dimensions (EQ-5D)). Participants will then be randomised 1:1 to receive IPE (4 g/day) or placebo for 6 months. Follow-up visits will occur at 30 days (bloodwork and EQ-5D only) and 6 months. The primary endpoint is the change in FDG uptake in the ascending aorta from baseline to 6 months between IPE and placebo groups. Secondary endpoints include FDG uptake in the bone marrow, spleen, lungs and other vasculature, in addition to major adverse cardiac events and quality of life assessments. An initial lead-in cohort of 18 patients will be enrolled to assess recruitment, imaging feasibility and IPE tolerability prior to full trial enrolment. These patients will remain blinded and will be included in the final analysis (Vanguard design). The TIN-CAP trial has been approved provincially by the Clinical Trials Ontario Research Ethics Board (approval number: 5045). Participants will provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and conference presentations. NCT06710080.

BackgroundCommunity-acquired pneumonia (CAP) represents a substantial global health burden; however, the characteristics of its etiological spectrum remain incompletely defined. Targeted next-generation sequencing (tNGS) has significantly advanced the understanding of the etiological spectrum. This study aimed to investigate the pathogen characteristics in CAP patients across different age groups and severity levels based on tNGS results.MethodsWe retrospectively analyzed the etiological test results of 272 hospitalized CAP patients at the First Hospital of Shanxi Medical University (Taiyuan, China) from 2021 to 2024. Patients were stratified by age and Pneumonia Severity Index (PSI) score, and their clinical characteristics, etiological spectrum, and infection patterns were systematically evaluated.ResultsAmong the 145 patients included in the final analysis, 34.48% had simple infections, while 65.52% had multiple infections. Elderly patients (≥80 years) exhibited the highest proportion of mixed infections (81.82%), with the detection rates of viruses and fungi—such as Epstein-Barr virus, Human herpesvirus 5, Candida glabrata, and Candida albicans—increasing significantly with advancing age. Younger patients (18–39 years) were more susceptible to atypical pathogen infections (eg, Mycoplasma pneumoniae). The proportion of mixed infections in severe cases was significantly higher than that in mild cases (76.92% vs 59.14%), and triple co-infections (involving bacteria, viruses, and fungi) were significantly concentrated in the severe group. Significant specific differences in the composition of the etiological spectrum were also observed among different age and severity groups; for instance, the detection rates of Klebsiella spp. and Acinetobacter baumannii were higher in the elderly and severe groups, whereas atypical pathogens were mainly concentrated in the young group.ConclusionThe etiological spectrum of CAP exhibits significant differences across different age groups and disease severity levels. Therefore, stratified diagnosis and therapeutic strategies should be developed based on age and disease severity to optimize prognosis and reduce the misuse of antibiotics.

Omadacycline is an FDA-approved oral and intravenous treatment for adults with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection that demonstrates potent in vitro activity and in vivo efficacy versus Mycobacterium abscessus. A randomized, double-blind, placebo-controlled, multicenter phase 2 study of omadacycline monotherapy was conducted in adults with nontuberculous mycobacterial pulmonary disease (NTM-PD) caused by M. abscessus. Eligible patients meeting the diagnostic criteria for NTM-PD were randomized 1.5:1 to receive omadacycline 300 mg orally once daily or placebo for 84 days. Randomization was stratified by prior antibiotic treatment for M. abscessus (yes/no). Sixty-six patients were randomized (41 omadacycline, 25 placebo). At baseline, cough, fatigue, mucus production, shortness of breath, and throat clearing were the most bothersome and common symptoms (68.2%-95.4% of patients). For the primary endpoint, 34.1% and 20.0% of omadacycline and placebo patients, respectively, were responders by definition 1 (improvement in symptom severity at day 84 for at least half of baseline symptoms) and 34.1% and 12.0%, respectively, were responders by definition 2 (definition 1 plus no deterioration in severity of any baseline symptom). Key secondary and exploratory clinical and microbiological endpoints also favored omadacycline compared with placebo. Four (9.8%) patients discontinued omadacycline therapy due to a treatment-emergent adverse event (TEAE). The most frequent omadacycline-related TEAEs were gastrointestinal, particularly nausea. Results consistently favored omadacycline monotherapy over placebo across several endpoints in NTM-PD caused by M. abscessus. Omadacycline was well tolerated; nausea was the most frequent TEAE. Further investigations are warranted.

[This retracts the article DOI: 10.7759/cureus.103212.].

Letter to the Editor Regarding "A Clinicoradiological and Bacteriological Profile of Community-acquired Pneumonia in a Tertiary Care Center in Eastern India".

Mycoplasma pneumoniae, a globally prevalent cause of community-acquired pneumonia in children and young adults, is typically diagnosed using molecular methods, including DNA- or RNA-based nucleic acid amplification tests (NAATs). While RNA-based NAAT is considered to reflect the viability and replication status of M. pneumoniae, a direct comparison of the clinical performance between DNA- and RNA-based NAATs has been lacking. This study aimed to compare these NAATs in clinical pediatric M. pneumoniae samples and elucidate the reasons for their differential detection outcomes. This study analyzed clinical M. pneumoniae samples from pediatric patients across different sample types, seasons, age, and sex subgroups between January and December 2018. The underlying reasons for their differential detection outcomes were further elucidated through in vitro culture and cell infection models. A total of 3180 clinical samples were analyzed. The performance of DNA- and RNA-based NAATs showed specific disparities, particularly associated with sample type and patient age, but not with sampling season or patient sex. In vitro experiments revealed that M. pneumoniae-RNA (MP-RNA) has higher synthesis and degradation rates, whereas M. pneumoniae-DNA (MP-DNA) accumulates and is sustained longer in the growth dynamics of the pathogen. The differential nucleic acid kinetics of M. pneumoniae across respiratory microenvironments likely explain the observed variations in clinical detection. These findings may enable evidence-based selection of DNA- or RNA-based NAATs according to patient age and sample type, thereby improving the reliable detection of M. pneumoniae in children.

To determine whether dysregulated copper metabolism and cuproptosis contribute to acute lung injury (ALI), and to evaluate whether targeting copper homeostasis mitigates lung inflammation and injury. Integrative analysis of RNA-seq data from patients with severe community-acquired pneumonia revealed increased enrichment of copper metabolism-related gene sets and differential expression of cuproptosis-related genes. Notably, immune deconvolution of patient RNA-seq data demonstrated prominent macrophage enrichment, suggesting that macrophages represent a major cell group in which dysregulated copper metabolism may occur during ALI. In a lipopolysaccharide (LPS)-induced mouse ALI model, lung copper levels were elevated, accompanied by molecular features of cuproptosis, including increased DLAT oligomerization and destabilization of Fe-S cluster proteins. Pretreatment with the copper chelator tetrathiomolybdate alleviated lung injury and inflammatory response, while suppressing cuproptosis-related molecular features invivo. In alveolar macrophages, LPS challenge increased intracellular Cu+ concentration and promoted DLAT oligomerization, and impaired Fe-S protein stability. Mechanistically, both copper chelation and knockdown of upstream cuproptosis regulator reduced DLAT oligomerization, restored Fe-S proteins, alleviated mitochondrial dysfunction, and decreased CD86+ macrophage polarization. Importantly, altered expression of copper transporters was observed, suggesting a remodeling of copper metabolic homeostasis during ALI. This study identifies cuproptosis as a previously unrecognized driver of ALI, mechanistically linking copper dysregulation to mitochondrial damage and inflammatory activation of alveolar macrophages, and demonstrates the therapeutic benefit of copper chelation or cuproptosis suppression. Antioxid. Redox Signal. 00, 000-000.

BACKGROUND Pulmonary abscess is an uncommon complication of pneumonia in pediatric patients. Diagnosis is challenging because early manifestations frequently overlap with those of community-acquired pneumonia. Despite advances in imaging modalities and antimicrobial therapy, pediatric pulmonary abscess remains clinically relevant due to its variable presentation and the difficulty of early identification. This report of pediatric pulmonary abscess highlights clinical features and diagnostic tools that may inform clinical management. CASE REPORT We describe 2 pediatric patients with pulmonary abscess complicating pneumonia. The first was a 4-year-old girl with community-acquired pneumonia who developed a cavitary lesion in the left lower lobe accompanied by empyema, persistent fever, and progressive respiratory compromise despite initial therapy. The second was a 17-month-old boy with right multilobar pneumonia that was complicated by a large right upper lobe abscess and pleural effusion after prolonged febrile illness and multiple evaluations at other hospitals before referral to our institution. In both patients, limited conventional microbiological testing failed to identify a bacterial pathogen, underscoring the diagnostic challenges. Both patients were exclusively treated with intravenous antibiotics followed by oral therapy; surgical and interventional drainage were omitted. Outpatient follow-up at 2 to 6 months confirmed complete clinical recovery and full radiological resolution. CONCLUSIONS These cases emphasize the importance of considering pulmonary abscess as a complication of persistent or worsening pneumonia in children. Early recognition, appropriate imaging, and timely antimicrobial therapy adjustment are essential to prevent complications and support recovery. Individualized follow-up incorporating clinical and radiological assessment ensures complete resolution and appropriate therapeutic response monitoring.

Mycoplasma pneumoniae (MP) is a leading cause of pediatric community-acquired pneumonia, with clinical manifestations ranging from self-limiting disease to severe refractory pneumonia and long-term pulmonary sequelae. Three interrelated, partially overlapping yet still contested processes can explain the core pathogenic mechanisms of MP pneumonia (MPP). In the acute phase, immune dysregulation is characterized by excessive cytokine release and abnormal activation of innate and adaptive immune cells; however, the origin and regulation of this excessive inflammation remain controversial. During the immune evasion phase, MP employs multiple escape strategies, including adhesion proteins, CARDS toxins, and genomic plasticity, to circumvent host defenses, establish persistent infections, and further leave hidden dangers for acute phase inflammatory dysregulation and chronic phase structural remodeling. However, the exact molecular mediators remain unclear. Macrolide antibiotics remain the primary clinical treatment; however, therapeutic limitations persist owing to increasing drug resistance and the lack of immunopathological interventions. In the migration phase, sustained immune activation and abnormal repair processes persist even after pathogen clearance, resulting in chronic lung injury and fibrosis, with underlying immunological mechanisms still poorly understood. This review synthesizes current insights into immune dysregulation across the acute-to-chronic spectrum of MPP, identifies unresolved immunopathological bottlenecks, and highlights translational opportunities for immune-targeted interventions beyond antibiotics.