Search Results (9,546)

Background: Following a significant decline during the 2020–2021 SARS-CoV-2 pandemic, Mycoplasma pneumoniae (MP) experienced a resurgence across Europe in 2023–2024. Although macrolide-resistant MP has increased globally, severe disease can occur even in the absence of resistance, which highlights the importance of rapid molecular characterization for clinical purposes. In this context, clinical severity is often improperly used as a surrogate marker of macrolide resistance, potentially driving unnecessary antibiotic escalation. Methods: We report a severe MP pneumonia occurring during the 2023–2024 resurgence and evaluate macrolide resistance through a rapid two-step workflow (Real Time-PCR screening for A2063G/A2064G followed by confirmatory 23S rRNA sequencing), to assess whether severity predicts resistance and to support antibiotic stewardship. Results: The patient developed acute hypoxic respiratory failure (PaO₂ 54.9 mmHg; P/F ratio 110), extensive centrilobular micronodules on chest CT imaging, significant systemic inflammation and elevated liver enzymes. Respiratory support was escalated from a Venturi mask to a high-flow nasal cannula and BiPAP. MP infection was confirmed by multiplex Real Time-PCR (RT-PCR) and supported by positive IgM/IgG serology. RT-PCR targeting A2063G/A2064G mutations revealed no resistance-associated variants, and Sanger sequencing of an 807 bp 23S rRNA fragment confirmed a wild-type genotype. Despite severe hypoxemic respiratory failure, no resistance-associated variants were detected, documenting a clear severity–genotype mismatch. Clinical and radiological improvement followed second-line antibiotic therapy. Conclusions: Severe MP pneumonia can occur despite the absence of macrolide resistance. During MP re-emergence, clinical severity should not be used to infer macrolide resistance. Integrating nucleic acid amplification test (NAAT) diagnosis with rapid genotyping/confirmatory 23S rRNA sequencing can prevent misclassification, reduce unwarranted broad-spectrum escalation, and strengthen antimicrobial stewardship decisions. Full article

Next-generation vaccines are being developed to elicit durable and cross-protective immune responses against diverse pathogens, particularly those targeting the respiratory and enteric systems. By strategically engaging T cell-centric antigen design, mucosal immune engagement, and induction of trained innate immunity, these innovative platforms are expected to reshape the paradigm of immunoprophylaxis and to offer promising avenues for enhanced protection against complex infectious diseases. Conventional antibody-based vaccines, though effective against many infections, often lack the capacity to induce durable or cross-protective immunity at mucosal surfaces. Advances in antigen design, delivery platforms, and adjuvant technologies now facilitate precise activation of tissue-resident memory T cells and enhancement of mucosal secretory IgA responses, thereby achieving sterilizing immunity at barrier surfaces while reinforcing systemic immune protection. Advanced delivery platforms, including lipid nanoparticles, viral vectors, and nano or liposomal carriers, further refine antigen presentation, enhancing stability, targeting, and overall immunogenicity. Concurrently, progress in understanding trained innate immunity highlights opportunities to induce broad, non-antigen-specific protection through epigenetic and metabolic reprogramming of innate cells. The integration of these adaptive and innate mechanisms may enhance early pathogen control, limits transmission, and strengthens defense against variant and antimicrobial-resistant pathogens across diverse populations. However, translating these immunological insights into safe, scalable, and globally accessible vaccines remains a major challenge. This review explores the emerging conceptual framework of next-generation vaccines that demonstrate partial integration of these axes in preclinical models, though human translation and functional synergy require Phase II validation. It highlights progress toward next-generation vaccines leveraging integrated adaptive and innate immune reprogramming for superior protection against respiratory and enteric pathogens. Full article

Periventricular nodular heterotopia (PVNH) is a genetically heterogeneous malformation of cortical development with variable neurological outcomes. Among recessive forms, ARFGEF2-related disorder is uniquely characterised by the association of diffuse PVNH and progressive microcephaly. We describe a two-year-old boy born to consanguineous parents who presented with severe developmental delay, hypotonia, progressive microcephaly, and infantile-onset epileptic spasms with developmental regression. Brain MRI showed extensive bilateral PVNH associated with callosal hypoplasia and ventriculomegaly. EEG revealed dysmature background activity with multifocal epileptiform discharges and runs of asynchronous fast activity during sleep. Genetic testing identified a novel homozygous nonsense variant in ARFGEF2. The clinical course was characterised by drug-resistant epilepsy and multisystemic involvement, including feeding difficulties and recurrent respiratory infections. To contextualise this case, we performed a comprehensive review of previously reported patients, further delineating the clinical, neuroradiological, and electroclinical spectrum of ARFGEF2-related disorder. This case highlights progressive microcephaly as a key distinguishing feature of ARFGEF2-related PVNH and underscores the importance of early genetic diagnosis to guide targeted surveillance for extra-CNS complications and multidisciplinary care. Full article

Background: The relationship between allergic status, SARS-CoV-2 infection, Long COVID, and post-restriction respiratory outcomes in children remains incompletely understood. This study aimed to explore the associations between allergic status and Long COVID, as well as between SARS-CoV-2 vaccination and post-restriction changes in allergic rhinitis (AR), asthma, and upper respiratory infections, in a pediatric tertiary-care cohort. Methods: We conducted a single-center, questionnaire-based observational study involving children aged 0–16 years, who were followed at the Pediatric Allergy Clinic of Umberto I Hospital in Rome. Parents completed an email-based questionnaire addressing SARS-CoV-2 infection, vaccination, persistent post-infectious symptoms, allergic diseases, and respiratory infections following restrictions. Analyses of Long COVID were limited to children with confirmed SARS-CoV-2 infection. Results: A total of 214 questionnaires were analyzed. Allergic status was not significantly associated with SARS-CoV-2 infection in the overall cohort. Among infected children, allergic status was independently associated with higher odds of Long COVID (adjusted OR 3.12, 95% CI 1.20–8.09; p = 0.019). Severe acute infection was also strongly associated with Long COVID (adjusted OR 6.84, 95% CI 2.72–17.21; p < 0.001). Complete vaccination was associated with lower odds of SARS-CoV-2 infection in the overall sample (adjusted OR 0.20, 95% CI 0.09–0.46; p < 0.001) but was not independently associated with Long COVID among infected children. After the removal of COVID-19 restrictions, 90.1% of allergic children reported worsening AR and 52.0% reported worsening asthma, with no significant association with SARS-CoV-2 infection or Long COVID. Group A Streptocossus (GAS) pharyngitis was reported in 50.0% and viral pharyngitis in 10.7% of the cohort, with no significant differences between allergic and non-allergic children. Conclusions: In this single-center, questionnaire-based pediatric cohort, allergic status was correlated with increased likelihood of Long COVID among children with confirmed SARS-CoV-2 infection; however, it was not associated with a higher risk of infection itself. Complete vaccination was linked to a reduced risk of infection, whereas no independent correlation with Long COVID was identified. Post-restriction exacerbation of allergic respiratory symptoms was prevalent, while the incidence of bacterial and viral pharyngitis did not vary significantly according to allergic status. Full article

Pharmacomicrobiomics is the study of drug–microbiome interactions. It examines the dynamic relationship between the drug, the host, and the microbiome, and has become a rapidly evolving area in the realm of pharmacology and personalized medicine. Emerging evidence demonstrates that the gut microbiome can influence the pharmacodynamics and pharmacokinetics of drugs through various mechanisms, while drugs can simultaneously alter microbial composition. Treatment approaches include regular targeted pharmaceutical therapies (e.g., antibiotics, antidepressants) and alternative treatment approaches (e.g., CAM treatments such as supplements and herbs). Microbiome-based medication treatment is an alternative treatment approach that has been studied extensively in the last decade. This article reviews the current knowledge on drug–microbiome interactions across multiple therapeutic systems, including cardiovascular, central nervous system, gastrointestinal, respiratory, endocrine, oncologic, musculoskeletal, anti-infective therapies, and supplements (such as melatonin). We also highlight the various pathways by which microbes can alter the mechanisms (such as drug absorption), bioavailability, efficacy, and incidence of adverse effects, along with highlighting the clinical implications of drug-induced dysbiosis. Full article

Background: Respiratory infections in critically ill patients remain a major challenge in intensive care units (ICUs), with high morbidity and mortality. Conventional microbiological methods often fail to identify the causative pathogen promptly, particularly in patients previously exposed to antibiotics. Multiplex molecular platforms, such as the BioFire FilmArray^® Pneumonia Panel Plus (FAPP), allow rapid detection of multiple respiratory pathogens and resistance markers, potentially improving early therapeutic decision-making. The objective of this work is to evaluate the impact of implementing FAPP on antimicrobial therapeutic decisions in critically ill patients with suspected respiratory infection. Methods: We conducted a retrospective cohort study in two mixed ICUs between 2023 and 2024. All respiratory samples in which FAPP was requested were analyzed. The results were compared with conventional cultures, and changes in antimicrobial therapy following the FAPP results were assessed, classified as escalation/initiation or de-escalation/discontinuation. Concordance between FAPP and culture was evaluated, and clinical and demographic variables were analyzed. Differences between groups were assessed using p-values obtained from the chi-square test or the Mann–Whitney test. Results: A total of 363 respiratory samples were included, 88.4% from mechanically ventilated patients. FAPP was positive in 65.3% of samples, whereas cultures were positive in 23.1%. Overall concordance between FAPP and culture was 57.3%. In 42.4% of cases, pathogens were detected exclusively by FAPP. Antimicrobial therapy was modified in 29.8% of patients, predominantly through de-escalation or discontinuation (69.4% of changes). Therapeutic modifications were more frequent in nosocomial infections and in patients with a positive FAPP result. Conclusions: The use of FAPP in critically ill patients with suspected respiratory infection provides rapid microbiological information that significantly influences antimicrobial decision-making, particularly by facilitating antibiotic de-escalation. Although discrepancies with conventional cultures remain and require careful clinical interpretation, FAPP represents a valuable tool for antimicrobial stewardship in the ICU setting. Full article

Primary Epstein–Barr virus (EBV) infection in children exhibits substantial clinical heterogeneity, often complicating early diagnosis and leading to unnecessary antibiotic use. This retrospective study evaluated 695 children (0–18 years) diagnosed with primary EBV infection at a tertiary pediatric center between 2010 and 2015, defined by positive viral capsid antigen (VCA) IgM and negative Epstein–Barr nuclear antigen (EBNA) IgG. Clinical, laboratory, and ultrasonographic findings were compared according to age group (≤4 vs. >4 years) and clinical setting (inpatient vs. outpatient). The median age was 3.75 years (IQR: 2–6.25), and more than half of the patients were ≤4 years. Younger children more frequently presented with nonspecific respiratory and gastrointestinal symptoms, whereas older children more commonly exhibited the classic infectious mononucleosis (IM) phenotype, including sore throat, dysphagia, lymphadenopathy, and hepatosplenomegaly (p < 0.001). Antibiotics were prescribed in 64.2% of patients, while 21.7% required hospitalization. Multivariable logistic regression analyses demonstrated that age was not an independent predictor of hospitalization, classic IM phenotype, or antibiotic use. Instead, specific clinical and laboratory findings—such as lymphopenia, lymphadenopathy, vomiting, thrombocytosis, and tonsillar hypertrophy—emerged as the key determinants of clinical outcomes. To enhance diagnostic discrimination, receiver operating characteristic (ROC) analysis of ANC/ALC and AST/ALT ratios was performed, and a composite risk score (0–2) was derived. Although both markers showed modest discriminative ability (AUC 0.607 and 0.575), their high negative predictive values (>90%) suggest potential utility as rule-out tools. The composite score demonstrated a stepwise increase in the probability of classic IM presentation across age groups. In conclusion, primary EBV infection demonstrates a clear age-related clinical spectrum; however, clinical and laboratory features rather than age alone drive key outcomes. These findings highlight the need for age-specific diagnostic strategies and improved antimicrobial stewardship, while the proposed risk score provides a foundation for future validation studies. Full article

Respiratory disease remains one of the mostly costly challenges in the U.S. swine industry and is frequently associated with polymicrobial infections. Routine qPCR assays are highly sensitive but are limited in multiplexing capacity and generally do not provide sequencing information for pathogen characterization. We hypothesized that a target next-generation sequencing (tNGS) panel could provide the broad, simultaneous detection of swine respiratory pathogens while preserving clinically relevant sensitivity. A multiplex Ion Torrent tNGS panel was developed and analytically validated using 20 serially diluted qPCR-positive clinical samples and synthetic gBlock controls, followed by diagnostic validation with 25 qPCR positive and 25 qPCR negative respiratory samples. Most targets were detected across clinically relevant pathogens concentrations. Actinobacillus suis primers showed nonspecific amplification, streptococcus suis serotyping was not consistently achievable in clinical samples, and porcine reproductive and respiratory syndrome virus typing was limited to distinguishing North American and European genotypes. Diagnostic agreement with routine qPCR was high (Cohen’s κ = 0.84), although sensitivity decreased for low-abundance targets. The assay detected mixed infections and additional organisms outside routine qPCR panels. These findings support tNGS as a complementary diagnostic and surveillance tool for swine respiratory disease. Full article

This study examined alterations in serum redox biomarkers before and one month after administration of the coronavirus disease 2019 (COVID-19) booster (third) doses across four vaccine regimens. A longitudinal cohort of 410 adults was analyzed following homologous Pfizer-BioNTech, Sinopharm [Vero Cell]-Inactivated, Sputnik V, or heterologous Sinopharm/Pfizer vaccination. Serum total proteins, albumin, total thiols, nitrites, ferric-reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity were measured, with DPPH interpreted as an ex vivo surrogate of serum radical-scavenging capacity. Additional analyses included stratification by prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, multivariable regression, correlation analysis, effect-size estimation, and sensitivity testing. Booster vaccination was associated with modest but consistent decreases in DPPH activity, albumin, and total proteins, whereas FRAP, nitrite, and total thiol levels remained stable. This pattern supports a transient shift in antioxidant buffering capacity but, by itself, does not exclude oxidative stress, as direct oxidative damage markers were not assessed. The most pronounced changes were observed in Sinopharm-based regimens, particularly in the heterologous Sinopharm/Pfizer group. Prior SARS-CoV-2 infection did not materially alter the qualitative response pattern, whereas older age and comorbidities were associated with greater declines in DPPH activity and albumin. Overall, the findings indicate a modest, transient redox-associated response following booster-induced immune activation and suggest that host-related factors, such as age and comorbidity burden, may accentuate short-term changes in antioxidant buffering capacity. Full article

Background and Objectives: Healthcare-associated infections (HAIs) remain a major cause of morbidity and mortality among hospitalized patients. During the COVID-19 pandemic, SARS-CoV-2 infection emerged as a major contributor to HAIs, alongside Clostridioides difficile infection (CDI) and other bacterial infections. This study aimed to evaluate the clinical characteristics and outcomes of HAIs in surgical departments and to identify factors associated with in-hospital mortality. Materials and Methods: We conducted a retrospective observational study including 170 patients with documented HAIs admitted between July 2018 and June 2022 in surgical departments of a county emergency hospital. Patients were categorized into SARS-CoV-2 infection (n = 85), CDI (n = 73), and other bacterial infections (n = 12), the latter being included for descriptive purposes only due to limited sample size. Clinical variables, comorbidities, prior antibiotic exposure, length of hospital stay, and in-hospital mortality were analyzed. Survival analysis and logistic regression were performed to identify predictors of mortality. Results: SARS-CoV-2 infection represented the largest subgroup, followed by CDI. Overall, in-hospital mortality was 15.9%, with comparable rates between SARS-CoV-2 infection (17.6%) and CDI (16.4%), while no deaths were observed in the small subgroup of other bacterial infections. CDI patients had a significantly higher burden of comorbidities (p = 0.004). Kaplan–Meier analysis did not show a statistically significant difference in survival between SARS-CoV-2 and CDI groups (log-rank p = 0.28). In univariate analysis, acute respiratory failure (OR ≈ 13.5, p < 0.001), chronic kidney disease (OR ≈ 4.4, p = 0.018), and number of comorbidities (p = 0.019) were associated with mortality, but none remained significant in multivariable analysis. Conclusions: In-hospital mortality was similar between SARS-CoV-2 infection and CDI, highlighting the persistent clinical impact of CDI in hospitalized patients. Comorbidity burden and acute complications, particularly respiratory failure, were key determinants of mortality. These findings highlight the persistent clinical impact of CDI and the role of comorbidity burden and acute complications, particularly respiratory failure, in shaping in-hospital mortality. The absence of independent predictors in multivariable analysis should be interpreted cautiously given the limited sample size. Full article

Background: Data on influenza vaccine effectiveness (VE) against hospitalized severe acute respiratory infection (SARI), particularly in Asia, remain limited for the 2025/26 Northern Hemisphere influenza season. This study aimed to evaluate real-world VE against A(H3N2)-associated SARI hospitalization and provide timely, locally relevant evidence to inform seasonal influenza vaccination policy. Methods: A test-negative design was used to estimate VE against influenza A(H3N2)-associated SARI hospitalization in Beijing, China, from 10 November 2025 to 18 January 2026. VE was estimated by comparing the odds of influenza vaccination between case-patients (those who tested positive for A(H3N2)) with controls (those who tested negative for influenza). Results: Among 1883 enrolled SARI inpatients, 220 (11.7%) tested positive for influenza A(H3N2). Overall vaccination coverage was 11.4%, with the highest coverage observed among children aged 5–17 years (29.6%). Influenza positivity was higher among rural residents, patients with pneumonia or hypoxemia, and those with symptom onset in November. The adjusted overall VE was 7.5% (95% CI: −45.8% to 43.3%). Moderate VE was observed among children aged 5–17 years (45.4%, 95% CI: −33.6% to 79.5%), although the confidence interval included zero and the estimate was not statistically significant. Negative VE estimates were observed among younger children and older adults. Among patients with underlying respiratory conditions, VE was 75.4% (95% CI: −27.4% to 98.7%), although this estimate was also not statistically significant. Conclusions: During the 2025/26 influenza season in Beijing, VE against A(H3N2)-associated SARI hospitalization was suboptimal. Moderate protection was observed among children aged 5–17 years, the group with the highest vaccination coverage, but the estimate was not statistically significant. The low overall VE may be attributable to antigenic mismatch between vaccine and circulating strains, as well as low population-level vaccination coverage. These findings highlight the need to improve vaccine formulations and increase vaccination coverage, particularly among adults and older populations. Full article

Post-infectious bronchiolitis obliterans (PiBO) is a chronic lung disease that develops after severe lower respiratory infections and leads to persistent inflammation and fibrotic changes in the small airways. In the present study, gene expression analysis was used to identify differentially expressed genes (DEGs) in sputum cells derived from PiBO patients and compare them to healthy controls. Clinical history, lung function parameters, and induced sputum samples were collected from nine patients with PiBO and eight healthy controls. Multiplex immunohistochemistry (mIHC) as well as mRNA sequencing (MACE-Seq) were performed. Evaluation of the biological targets was done by KEGG pathway enrichment analysis. PiBO patients showed significantly reduced lung function parameters, an increased neutrophil count, and an altered macrophage profile in sputum. Transcriptome analysis revealed significant upregulation of the TNFα-dependent NFκB signalling pathway, as well as significant downregulation of the oxidative phosphorylation (OXPHOS). Linear regression analyses and mIHC indicated a shift in macrophage polarisation that may contribute to the dysregulated gene expression. Notably, expression of these DEGs significantly correlated with FEV₁ lung function. These findings indicate a central role of macrophages in the immunopathology of PiBO and contribute to our understanding of the molecular mechanisms involved in the disease process. Full article

The global prevalence of pulmonary infections caused by non-tuberculous Mycobacteria (NTM), particularly the Mycobacterium avium complex (MAC), is increasing. Since NTM are ubiquitous in moist environments and resistant to standard disinfectants, this study evaluated the efficacy of chlorous acid water (CAW) against them. CAW demonstrated superior sanitizing effects compared to sodium hypochlorite (NaClO), efficiently inactivating NTM at 100 mg/L free available chlorine even in the presence of organic matter, where 1000 mg/L NaClO failed. Instead, subcellular fractionation and protein analysis revealed that CAW penetrates the cell to induce extensive aggregation of internal functional proteins, leading to the rapid collapse of membrane potential and ATP production. Furthermore, CAW exhibited significantly lower cytotoxicity toward human lung-derived A549 cells than NaClO. These results indicate that CAW inactivates NTM effectively by targeting internal protein stability and the respiratory chain, offering a potent and safer disinfection strategy for clinical and domestic environments. Full article

Antimicrobial resistance (AMR) in companion animals is an escalating concern at the interface of veterinary medicine and public health. Dogs and cats, the most commonly treated companion species, are frequently prescribed antimicrobials for dermatological, otic, urinary, and respiratory infections—often involving drug classes that are critically important in human medicine. This overlap underscores the need for judicious use and integrated stewardship within a One Health framework. This narrative review synthesizes current evidence on AMR in companion animals and its implications for One Health. Studies were included if they reported AMR in dogs and cats and addressed zoonotic aspects. Staphylococcus pseudintermedius, S. aureus, Escherichia coli, Pseudomonas aeruginosa, and Enterococcus sp. are examples of clinically significant organisms that are becoming more resistant to several antibiotic classes, which can result in treatment failures and extended illness. Horizontal gene transfer facilitates the spread of resistance determinants across bacterial populations. Improved surveillance systems, prudent antibiotic use, regular culture and susceptibility testing, and enhanced antimicrobial stewardship in veterinary practice are just a few of the many strategies needed to address AMR in companion animals. The integration of companion animals into AMR surveillance, stewardship programs, and infection control strategies is essential. Coordinated One Health interventions are urgently required to mitigate the spread of AMR. Full article

Background/Objective: Respiratory syncytial virus (RSV) is an often under-recognized cause of respiratory illness in older adults. Clinical overlap with bacterial infections and delayed virologic confirmation may lead to the unnecessary prescription of antibiotics and antimicrobial resistance (AMR). This systematic review was conducted to assess antibiotic prescription in older adults with RSV and the factors influencing these decisions. Methods: This systematic review was preregistered in PROSPERO (CRD42024586905) and reported according to PRISMA guidelines. PubMed/MEDLINE, Embase, Web of Science, Cochrane CENTRAL, and Scopus were searched for studies published between January 2000 and August 2025. Eligible studies were those including adults aged ≥60 or ≥65 years with RSV infection and reporting antibiotic use. Data on antibiotic prescription, confirmed bacterial infection, hospitalization, length of stay (LOS), and prescribing indications were extracted. Results: Eight observational studies across inpatient, outpatient, emergency, and primary-care settings were included. Antibiotic prescribing ranged from 40.0% to 97.7%, whereas confirmed bacterial infection did not exceed 20% in any study. Antibiotic prescribing was associated with diagnostic uncertainty, radiologic findings, inflammatory markers, respiratory distress, delayed RSV testing, and multimorbidity rather than microbiological confirmation. Hospitalization rates varied across settings, and the LOS ranged from 3.5 to 11 days. None of the studies reported antibiotic discontinuation following RSV confirmation. Conclusions: Older adults with RSV frequently receive antibiotics despite low rates of confirmed bacterial infection, indicating substantial empirical prescribing. Improved rapid diagnostics, reassessment of therapy, and strengthened antimicrobial stewardship may help reduce unnecessary antibiotic use. RSV vaccination may be a promising strategy for reducing severe disease and hospitalization, with a potential indirect effect on antibiotic use, although these effects remain hypothetical. Full article