Search Results (747)

Background/Objectives: Respiratory syncytial virus (RSV) causes morbidity in older adults with cardiovascular disease, in whom infection may precipitate severe lower respiratory tract disease, hospitalization, functional decline, and cardiovascular destabilization. We evaluate the evidence for RSV vaccination in cardiovascular disease and propose a jurisdiction-adaptable framework for integrating vaccination into cardiovascular care. Methods: Observational studies, randomized trials, pragmatic and test-negative studies, prespecified cardiovascular analyses of DAN-RSV, and eligibility recommendations were narratively synthesized and translated into a pathway encompassing patient identification, eligibility and risk assessment, vaccine delivery and co-administration, documentation, and follow-up. Results: Acute cardiac events are frequent during RSV hospitalization, and cardiovascular risk may persist after infection. Randomized trials establish protection against RSV-associated lower respiratory tract disease and respiratory illness, while real-world studies support effectiveness against RSV-related hospitalization. DAN-RSV reduced all-cause cardiorespiratory hospitalization but did not demonstrate significant reductions in cardiovascular hospitalization, myocardial infarction, heart failure (HF) hospitalization, atrial fibrillation, stroke, cardiovascular death, or major adverse cardiovascular events; observational associations with lower post-vaccination cardiovascular-event rates remain hypothesis-generating. The framework prioritizes adults aged ≥75 years and those aged 50–74 years with high-risk cardiovascular conditions where consistent with national recommendations, embeds vaccination assessment across cardiology, HF, primary care, pharmacy, and long-term care, and incorporates co-administration, documentation, and outcome surveillance. Conclusions: The principal contribution is a pathway for moving RSV vaccination from recommendation to routine preventive care for adults with cardiovascular disease. It anchors implementation in established RSV and cardiorespiratory benefits while treating cardiovascular-event reduction as a research priority rather than a demonstrated indication. Full article

Background: Legionnaires’ disease (LD) is most often described as caused by a single Legionella pneumophila (Lp) serogroup (SG), typically SG1. However, mixed infections involving multiple SGs or even different Legionella species can occur within a single host. Such cases remain underrecognized and pose challenges for diagnosis, clinical management, and outbreak investigation. Case presentation: A 61-year-old woman developed acute fever, malaise, and productive cough after visiting a wellness spa in France, with radiological findings consistent with a lower respiratory tract infection. The urinary antigen test (UAT) for Lp was negative, but respiratory multiplex PCR was weakly positive. Subsequent testing at the Belgian National Reference Centre (NRC) for Legionella revealed an unexpected discordance between an in-house SG1-specific PCR and culture-based findings. Further analysis identified co-infection with two distinct Lp strains, SG1 (sequence type, ST146) and SG10 (ST1267), using a combination of direct sequence-based typing (SBT) and culture with serogrouping of multiple colonies. The patient improved rapidly after treatment with oral levofloxacin. Conclusions: Mixed Lp SG infections are likely underrecognized in routine practice, as neither UAT, commercial molecular assays, nor characterization of a single cultured isolate may adequately capture within-host strain diversity. Comprehensive diagnostic approaches combining culture with analysis of multiple colonies and molecular tests are essential for accurate case detection and source attribution. Referral to NRCs is recommended when advanced typing methods are unavailable. This first reported Belgian case illustrates the potential implications for patient management and epidemiological investigations, underscoring the need for broader diagnostic strategies. Full article

Background/Objectives: Targeted pulmonary delivery of antibiotics offers a favorable approach for the treatment of lower respiratory tract infections (LRTIs) by enhancing local drug concentrations while minimizing systemic exposure. This study aimed to develop and characterize fatty acid-based nanostructured lipid carrier (NLC) microparticles, including tobramycin-loaded formulations, and assess their potential application as carriers for pulmonary drug delivery. Methods: Tobramycin-loaded NLC microparticles were prepared using a hot emulsification method, with lauric acid as the solid lipid and oleic acid as the liquid lipid. The obtained formulations were characterized in terms of morphology, particle size distribution, zeta potential, thermal properties, encapsulation efficiency, drug-release behavior, aerodynamic properties, and powder flowability. Antibacterial activity was evaluated against S. aureus and P. aeruginosa, while cytocompatibility was assessed using BEAS-2B human-lung epithelial cells. Results: The developed microparticles exhibited spherical morphology, with particle characteristics influenced by lipid composition. Incorporation of oleic acid increased tobramycin encapsulation efficiency, reaching approximately 75% at liquid lipid concentrations of 5–15%. Theoretical aerodynamic diameters remained within the respirable range, and increasing oleic acid content improved powder flowability. Drug-release behavior was strongly dependent on lipid composition, with the optimized formulation providing prolonged tobramycin release over 72 h. All formulations preserved antibacterial activity against S. aureus and P. aeruginosa and demonstrated good cytocompatibility with BEAS-2B cells. Conclusions: Fatty acid-based nanostructured lipid microparticles represent a promising active carrier platform for the pulmonary delivery of tobramycin. The developed system demonstrated efficient drug encapsulation, satisfactory particle characteristics, controlled drug release, preserved antibacterial activity, and good biocompatibility, making them a suitable component of dry powders for inhalation (DPI). Full article

Background/Objectives: Acute lower respiratory infections (ALRIs) are an important cause of morbidity among children under five years of age. This study aimed to identify factors associated with ALRI among children under five treated at a Peruvian emergency hospital. Methods: We conducted an observational, analytical, retrospective cross-sectional study using medical records of children treated in the pediatric emergency department of Hospital de Emergencias José Casimiro Ulloa, Lima, Peru, between January and December 2024. ALRI was defined as a physician-recorded diagnosis of pneumonia or bronchiolitis; the comparison group comprised children with acute bronchitis or upper respiratory tract infection. Crude and adjusted prevalence ratios (PRs) with 95% confidence intervals (CIs) were estimated using Poisson regression with robust variance. Results: The final sample included 322 children, of whom 154 (47.8%) had ALRI. In the adjusted model, age 0 to <2 years (aPR = 1.27; 95% CI: 1.03–1.56), absence of exclusive breastfeeding (aPR = 1.24; 95% CI: 1.02–1.51), birth weight < 1000 g (aPR = 1.43; 95% CI: 1.09–1.87), incomplete immunizations (aPR = 1.28; 95% CI: 1.07–1.53), and passive smoking exposure (aPR = 1.38; 95% CI: 1.15–1.65) were independently associated with higher ALRI prevalence. Conclusions: ALRI accounted for nearly half of the ARI diagnoses in this pediatric emergency analytical sample. Younger age, absence of exclusive breastfeeding, extremely low birth weight, incomplete immunizations, and passive smoking exposure were independently associated with ALRI and may help identify children requiring closer clinical assessment and preventive interventions. Full article

Background/Objectives: Acinetobacter baumannii is a major cause of infections in Intensive Care Units (ICUs), driving mortality through high-level antimicrobial resistance. This study utilized whole-genome sequencing (WGS) to evaluate the phenotypic, genotypic and virulence features of carbapenem-resistant A. baumannii (CRAB), which has caused ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) in the ICU of the University Hospital of Split, Croatia. Methods: Over 1 year, lower respiratory tract specimens from 79 VAP/VAT patients were analyzed. CRAB isolates were identified via MALDI-TOF MS and evaluated for antimicrobial susceptibility, and a representative subset underwent WGS and multilocus sequence typing (MLST). Results: Out of 106 specimens, 18 non-duplicate CRAB strains were isolated. Five isolates underwent genomic analysis, identifying two globally distributed, high-risk Pasteur lineages: ST2 and ST492. These lineages displayed distinct resistomes: ST2 carried bla_OXA-23 and bla_ADC-73, while ST492 harbored plasmid-borne bla_OXA-72 (Rep3-T1/AB082 cluster) and bla_ADC-30. All isolates shared aminoglycoside/macrolide-resistance genes, conserved efflux pumps, and virulence determinants (bau, bas, ent, bar) crucial for acinetobactin synthesis and respiratory colonization. Phylogenetic analysis confirmed regional circulation and genetic links to neighboring countries. Conclusions: This study highlights the evolutionary dynamics of endemic CRAB lineages in a Croatian ICU and their global dissemination, which poses a critical threat, demanding strict infection control and novel therapeutics. Full article

Background: Upper airway tract infections (UATIs) are among the most common infectious diseases worldwide, accounting for an estimated 12.8 billion episodes annually and more than 8 million disability-adjusted life years (DALYs). Despite their generally self-limiting nature, their cumulative clinical, socioeconomic, and public health burden remains substantial, particularly in children, older adults, and low- and middle-income countries (LMICs). Methods: We performed a structured narrative review of the peer-reviewed literature and reports from major international health organizations to summarize the current evidence on the epidemiology, etiology, clinical impact, socioeconomic burden, prevention strategies, and future challenges associated with UATIs. Particular attention was given to the influence of antimicrobial resistance, vaccination policies, and lessons learned from the COVID-19 pandemic. Results: UATIs remain one of the leading causes of healthcare utilization worldwide. Children experience the highest incidence, averaging 6–8 episodes annually, whereas vulnerable populations are at increased risk of complications and hospitalization. Marked geographical disparities persist, with LMICs experiencing a disproportionate burden due to limited healthcare access, lower vaccination coverage, and higher complication rates. Inappropriate antibiotic prescribing continues to accelerate antimicrobial resistance, while the COVID-19 pandemic profoundly altered the epidemiology of respiratory infections and demonstrated the effectiveness of non-pharmaceutical interventions. Advances in vaccination, antimicrobial stewardship, rapid diagnostics, and novel therapeutic strategies offer promising opportunities to reduce disease burden. Conclusions: Reducing the global burden of UATIs requires integrated public health strategies combining equitable vaccine access, effective antimicrobial stewardship, strengthened healthcare systems, and sustained surveillance. Lessons learned from the COVID-19 pandemic provide a unique opportunity to improve preparedness for future respiratory outbreaks while addressing persistent regional inequalities in prevention and care. Full article

Background: Acute bronchiolitis is among the most common causes of lower-respiratory-tract infection in infancy and remains a clinically heterogeneous syndrome. Current international guidelines recommend supportive management and generally discourage routine bronchodilator administration; however, a subset of patients may be physiologically responsive. Tidal-breathing analysis (TBA) is a non-invasive, bedside method for objectively assessing respiratory mechanics and may objectively quantify physiological changes following bronchodilator administration in older children. Case Presentation: We report the case of a 23-month-old boy presenting with a severe RSV bronchiolitis-like wheezing illness complicated by acute respiratory failure. Bronchodilator responsiveness was evaluated using predefined TBA parameters before and after administration of an inhaled bronchodilator. Following treatment, the patient’s time to peak tidal expiratory flow (tPTEF) increased from 0.17 to 0.33 s (+94%), while his tPTEF/TE ratio increased from 0.12 to 0.27 (+125%). Expiratory time (TE) and total respiratory cycle duration (Ttot) decreased by 12.6% and 5.1%, respectively, whereas tidal volume (VT) and minute ventilation (MV) increased by 12.1% and 18.3%. Peak expiratory flow remained unchanged (0.14 L/s before and after bronchodilator administration). Discussion: To the best of our knowledge, this is among the first reports of using bedside TBA to characterize acute bronchodilator responsiveness in a severe bronchiolitis-like illness. The improvement in expiratory timing indices, along with the shorter expiratory time without changes in peak expiratory flow, is consistent with improved expiratory flow dynamics following bronchodilator administration. These findings could support the hypothesis that a bronchodilator-responsive physiological phenotype may exist. Previous studies have demonstrated an association between severe bronchiolitis during infancy and subsequent recurrent wheezing or asthma; however, whether acute bronchodilator responsiveness, measured objectively via TBA, is an indication of this phenotype represents a testable hypothesis for future longitudinal studies. Conclusions: This case illustrates the feasibility of bedside TBA for identifying physiological bronchodilator responsiveness in severe bronchiolitis-like illness. Prospective longitudinal studies should be conducted to determine whether TBA-defined responsiveness represents an early physiological marker requiring prospective validation and whether such physiological stratification may support individualized follow-up strategies. Full article

Lower respiratory tract infections caused by the respiratory syncytial virus (RSV) pose a major global public health challenge. The use of next-generation sequencing technologies enables detailed monitoring of viral genetic variability, which is crucial for evaluating the efficacy of immunoprophylactic measures. In this study, whole-genome sequencing of RSV was performed on 106 samples collected in the Russian Federation between September 2021 and April 2025. Three NGS platforms were employed: Illumina MiSeq, Oxford Nanopore Technologies MinION, and Qitan Tech QNome-3841. Using discrete phylogeographic methods, we estimated a minimum of 45 introduction events into Russia for RSV-A and 39 for RSV-B among the genomes included in the analysis. Most events were represented by a single Russian genome. These results indicate recurrent introductions of RSV into Russia from abroad. Given the limited genomic sampling available, most of these introductions were not associated with detectable transmission within the country. Full article

Airborne transmission represents a primary route of influenza virus dissemination. In animal infection models, conventional intranasal instillation fails to recapitulate the physiological features of natural respiratory infection. Existing aerosol-based challenge methods—including whole-body inhalation and oronasal exposure—face limitations in precise quantification of the delivered infectious dose. Moreover, oronasal exposure systems require specialized, high-cost instrumentation. This study established an economical and dosing-controlled aerosol challenge method utilizing a lung fluid quantitative nebulizer, which can deliver aerosolized virus directly to the lower respiratory tract via endotracheal intubation. The count median aerodynamic diameter (CMAD) of aerosols generated by the nebulizer was 2.28 μm. We compared pulmonary deposition efficiency and pathogenicity between lung-delivery aerosol inhalation and conventional intranasal instillation of PR8 influenza virus in mice. The pulmonary deposition rate for the aerosol inhalation was 63.1%, with an LD₅₀ of 31.1 EID₅₀; in contrast, intranasal instillation achieved a pulmonary deposition rate of 20.0% and an LD₅₀ of 115.0 EID₅₀. Histopathological analysis revealed significantly more severe lesions in lungs of mice challenged via lung-delivery aerosol inhalation relative to those receiving intranasal instillation. Furthermore, using a guinea pig model and a recombinant PR8 virus expressing Gaussia luciferase (PR8-Gluc), we demonstrated that pulmonary aerosol inhalation resulted in both more homogeneous spatial distribution and higher viral loads across lung tissues. Our results demonstrate that animals are more sensitive to lung-delivery inhaled virus than virus delivered by intranasal instillation. This study provides an optimized, economical, and technically straightforward aerosol challenge method with controlled administered dosing for viral infection models. Full article

High-throughput metagenomic sequencing and advances in mucosal immunology have refuted the traditional physiological concept of a sterile respiratory tract. The oral cavity has been recognized as a dynamic determinant of systemic health. As in other parts of the body, recent studies also suggest that pulmonary health may be linked to oral health. Under eubiotic conditions, the oral microbiome maintains local immunological homeostasis and colonization resistance. Oral dysbiosis, characterized by sequential shifts in microbial communities and the proliferation of the pathogenic red complex (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia), induces a state of chronic systemic inflammation, potentially involved in an infectious axis between the oral cavity and the lung. This review evaluates the tripartite systemic pathways of metastatic infection, metastatic injury, and metastatic inflammation that govern the translocation of oral pathobionts and their bioactive components, including lipopolysaccharides, outer membrane vesicles, and matrix metalloproteinases, to the lower respiratory tract via microaspiration and hematogenous circulation. The clinical implications across the chronic respiratory disease spectrum are examined, with a focus on how deficits in oral microbial diversity influence chronic obstructive pulmonary disease (COPD) pathogenesis, modulate the pulmonary virome and mycobiome, and stimulate maladaptive trained immunity. Furthermore, the contribution of biological aging is assessed, highlighting the roles of immunosenescence, inflammaging, and physiological reflex decline within the broader mucosal continuum. Finally, the clinical translation of this axis is analyzed, emphasizing the integration of saliva-based point-of-care nano-theranostics, metatranscriptomic profiling, and targeted interventions—such as professional oral biofilm management in intensive care settings and precision microbiome engineering—to preserve respiratory function and restore immune homeostasis. Full article

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are clinically relevant pathogens in lung transplant (LT) recipients, but their impact on lung function and the benefit of ribavirin remains uncertain. We conducted a prospective multicenter observational cohort study of adult LT recipients with RSV or hMPV infection diagnosed between 2021 and 2024 at five centers, with follow-up for up to 12 months. Ribavirin was prescribed at the treating physician’s discretion. Multivariable analysis assessed the association between ribavirin and percentage change in forced expiratory volume in the first second (FEV₁) at 90 days, using FEV₁ three months before infection as baseline and adjusting for baseline FEV₁, pre-existing chronic lung allograft dysfunction, and time since transplantation. Seventy-six patients were included; 60 (78.9%) had RSV and 16 (21.1%) hMPV. Lower respiratory tract infection occurred in 48.7%, and an acute ≥10% FEV₁ decline at 14 days was observed in 29.3%. Among patients with lower respiratory tract infection, 45.9% received corticosteroids alone and 37.8% corticosteroids plus ribavirin. No statistically significant between-group differences in allograft dysfunction or mortality were observed. RSV and hMPV infections after LT were frequently associated with lower respiratory involvement and lung function decline. In this observational cohort, ribavirin use was not independently associated with 90-day FEV₁ change; however, residual confounding and limited statistical power preclude conclusions regarding treatment efficacy. Full article

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab, a long-acting monoclonal antibody, provides single-dose protection during the RSV season, but the effectiveness of prophylaxis programs depends on sustained parental acceptance and high uptake. This study evaluated changes in parental knowledge, perceptions, and willingness to accept nirsevimab across two consecutive RSV seasons in Emilia-Romagna, Italy. Methods: Two multicenter cross-sectional surveys were conducted during consecutive RSV seasons, 2024–2025 and 2025–2026, using a comparable questionnaire and recruitment approach. Parents or legal guardians of infants eligible for nirsevimab completed a semi-structured questionnaire during routine counseling in neonatal units. Survey 1 included 1042 respondents and survey 2 included 867 respondents. Sociodemographic characteristics, RSV awareness, knowledge and perception of nirsevimab, willingness to accept prophylaxis, trust in healthcare providers and the healthcare system, preferred information sources, and willingness to pay were compared between seasons. Results: Willingness to administer nirsevimab remained high and stable—87.04% in survey 1 and 88.00% in survey 2. Awareness of RSV-related risks increased from 68.23% to 73.47% (p < 0.05), and correct identification of nirsevimab as an antibody increased from 65.93% to 71.74% (p < 0.01). Explicit refusal rose slightly from 2.21% to 3.81% (p < 0.05). In survey 2, acceptance was associated with higher education, awareness of RSV risks, perceived child susceptibility, confidence in efficacy, lower concern about side effects, trust in pediatricians and the healthcare system, and willingness to pay. Notably, acceptance in 2025–2026 was higher among infants born in September–December than among those born in January–March, indicating a late-season decline. Conclusions: Parental acceptance of nirsevimab remained high across two seasons. Future campaigns should address residual knowledge gaps, reinforce communication on safety and efficacy, and sustain high coverage throughout the entire RSV season, particularly among infants born in its final months. Full article

Background/Objectives: Return to the pre-hospital residence is a meaningful patient-centered outcome after hospitalization for pneumonia or lower respiratory tract infection (LRTI). We examined factors associated with 30-day non-return, including prespecified baseline characteristics, the initial empirical antimicrobial therapy pattern, and initial treatment failure within 7 days. Methods: This retrospective observational study included 126 consecutive patients aged ≥65 years admitted with pneumonia or LRTI to a community-based general hospital in Japan. Patients who died within 48 h were excluded. Three multivariable logistic regression models were fitted: Model 1 evaluated prespecified baseline characteristics; Models 2 and 3 added the initial empirical antimicrobial therapy pattern and initial treatment failure within 7 days, respectively. Initial treatment failure was treated as a post-baseline marker of an unfavorable early clinical course. Results: The median age was 89.0 years, and 56 patients (44.4%) returned to their pre-hospital residence within 30 days. Higher serum albumin was associated with lower adjusted odds of non-return across all models (OR range, 0.365–0.407 per 1 g/dL increase). Initial treatment failure was associated with higher adjusted odds of non-return (OR, 3.296; 95% CI, 1.095–9.923), whereas the initial empirical antimicrobial therapy pattern showed no statistically significant overall association (global p = 0.859). The principal findings were materially unchanged in sensitivity analyses addressing early deaths and the treatment-failure definition. However, in other supportive analyses, the associations remained directionally consistent but were attenuated and no longer statistically significant in the analysis restricted to 30-day survivors; in addition, the serum albumin association in Model 3 did not retain statistical significance in some leave-one-out analyses. Conclusions: Higher serum albumin at admission was associated with lower odds of 30-day non-return, whereas initial treatment failure was associated with higher odds. Initial treatment failure should be interpreted as a post-baseline marker of an unfavorable early clinical course rather than as an independent baseline predictor. No statistically significant association with the initial empirical antimicrobial therapy pattern was detected. These findings do not establish causality. Full article

Background: Empiric antibiotic prescribing is frequently used in low- and middle-income countries because microbiological diagnostic capacity is often limited, highlighting the need for locally generated microbiological data to support evidence-informed empiric antibiotic selection. However, data on pediatric antibiotic prescribing practices in Mozambique remain scarce. This study aimed to characterize empiric antibiotic prescribing among hospitalized pediatric patients at Maputo Central Hospital prior to the implementation of a syndromic antibiogram intervention. Methods: An exploratory, retrospective, descriptive baseline analysis was conducted among pediatric patients aged 1 month to 14 years admitted with suspected bacterial infections between January and December 2023, prior to the implementation of a syndromic antibiogram intervention. Sociodemographic, clinical, microbiological, and antibiotic prescribing data were extracted from clinical records. Antibiotics were classified according to the WHO AWaRe framework, and associations between patient characteristics, treatment strategies, and outcomes were analyzed using R software version 4.6.0. Results: A total of 358 pediatric patients were included, with a median age of 14 months (IQR: 6–48), and 57% were male. Lower respiratory tract infections were the most frequent diagnosis. Empiric treatment predominated, accounting for 89% of cases, whereas microbiologically guided therapy was observed in only 11%. Urinary tract infections showed significantly higher proportions of microbiologically guided treatment compared with respiratory infections (p < 0.001). Monotherapy predominated, while Watch antibiotics accounted for 64.7% of prescriptions. Prolonged hospitalization was associated with respiratory distress, decreased skin turgor, referral status, infection type, and anemia. Conclusions: Pediatric antibiotic prescribing was characterized by extensive empiric therapy and high Watch antibiotic use, highlighting important antimicrobial stewardship challenges in Mozambique. Full article

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract infection in early infancy, with the highest burden concentrated in the first months of life. Two immunoprophylactic strategies—maternal RSVpreF vaccination and long-acting monoclonal antibodies—now offer effective early life protection, yet differ in biological mechanisms, operational requirements, and programmatic implications. Maternal vaccination induces high-quality neutralizing antibodies that are transferred transplacentally, providing immediate protection from birth and integrating efficiently into antenatal care platforms. However, its effectiveness is constrained by gestational timing, physiological antibody waning, and reduced protection when vaccination occurs shortly before delivery. Long-acting monoclonal antibodies, including nirsevimab and clesrovimab, bypass maternal immune variability and provide standardized, season-long protection across gestational ages, including preterm infants. Economic evaluations demonstrate that both strategies can be cost-effective, though their relative value depends on local epidemiology, pricing, and coverage patterns. Economic outcomes for monoclonal antibodies and maternal vaccination are highly context-dependent and influenced by regional RSV epidemiology, healthcare utilization, product pricing, and implementation capacity, rather than universally favoring one strategy over the other. Global equity considerations remain critical: disparities in antenatal care access, supply chain fragility, and pricing differentials may widen gaps between high- and low-income countries. Remaining evidence gaps—including long-term safety monitoring, durability of protection, viral evolution, and implementation challenges—underscore the need for continued research and careful integration of these tools into national immunization programs. Full article