Search Results (2,173)

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/Objectives: Candida species are among the leading causes of fungal infections, especially in immunosuppressed patients. In recent years, the increase in non-albicans species has altered the epidemiological landscape, requiring updated local surveillance data. Therefore, this study aims to analyze the epidemiological pattern of Candida spp. involved in various clinical manifestations. Methods: This was a retrospective observational descriptive study of clinical Candida isolates recovered from patients at a single tertiary care hospital in Puebla, Mexico, between 2021 and 2022. Sociodemographic and clinical data were collected from medical records. Candida spp. isolates were recovered from the hospital’s clinical specimen collection and identified using conventional methods and phylogenetic analysis. Results: Ninety isolates were recovered from a total of 88 patients during the study period. The majority of patients were women (60.2%), and among the age groups, the largest proportion corresponded to older adults (≥60 years, 25%). Candida was most frequently isolated from the urinary tract (47.7%), followed by the respiratory tract (19.3%) and the vulvovaginal tract (14.7%). Candida albicans was the predominant species (51.1%), followed by Nakaseomyces glabratus (32.2%) and other species such as Pichia kudriavzevii (5.5%), Candida tropicalis (3.3%), Candida dubliniensis (3.3%), Candida parapsilosis (2.2%), and Candida orthopsilosis (1.1%). The study showed discrepancies between conventional identification methods and molecular analysis. Of the 33 isolates evaluated using culture methods, only 21 matched the identification by PCR and phylogenetic analysis. In the case of the BD Phoenix automated system, 20 matches with and 13 discrepancies from the molecular tests were recorded. Conclusions: Our findings revealed the significant presence of species belonging to the non-albicans family in specific clinical contexts, highlighting the urgent need to monitor the epidemiological profile. The observed discrepancies between phenotypic and molecular identification methods suggest that species identification based solely on phenotypic approaches should be interpreted with caution. Full article

Enterovirus D68 (EV-D68) is a re-emerging pathogen associated with severe acute flaccid myelitis (AFM) and pneumonia, predominantly in children but also capable of causing severe disease in immunocompromised adults. Seroprevalence data are essential for understanding population immunity, age-specific susceptibility, and viral transmission dynamics; yet, such data for the period after the COVID-19 pandemic are scarce. We conducted a cross-sectional serological survey to characterize the neutralizing antibody profile of EV-D68 among children in Xiamen, China, in 2022. A total of 453 children aged 0–16 years (217 with acute respiratory tract infection [ARTI] and 236 without) were enrolled. Neutralizing antibody (NtAb) titers against the EV-D68 STL strain were measured using a microneutralization assay, seropositivity was defined as a titer ≥1:16. Multivariable regression and analysis of covariance were used to adjust for age and sex. Overall seroprevalence was 96.0% (435/453), exceeding 90.0% in every age subgroup (0–1 y: 100%; 1–3 y: 97.6%; 3–5 y: 92.6%; ≥5 y: 96.2%). The geometric mean titer (GMT) was 76.78 (95% CI: 68.32–85.24). After adjustment, ARTI status was not significantly associated with seropositivity (adjusted OR = 1.42, 95% CI: 0.46–4.41, p = 0.542). In an exploratory comparison, children with ARTI showed nominally higher antibody titers than those without (Mann–Whitney U test, p = 0.003), although the absence of EV-D68-specific PCR testing precludes etiologic attribution of respiratory symptoms to EV-D68 infection. Infants < 1 year showed the highest GMT (86.31), while children aged 1–3 years had the lowest GMT (63.52) and the largest low-titer fraction, indicating a susceptibility gap. Our study revealed EV-D68 circulated endemically in this pediatric population, establishing a high population immune baseline (>90.0%) with distinct age-dependent patterns. These findings provide key reference data for ongoing serosurveillance, outbreak risk assessment, and the evaluation of future vaccines or immunoprophylactic strategies should they become available. Full article

Pelargonium graveolens L’Hér. is a widely distributed aromatic plant that has been utilized in traditional medicine for an extended period. It is currently experiencing a surge in popularity in modern phytotherapy. The ethnopharmacological uses of this species include treatment of respiratory tract infections, digestive disorders, and analgesia. The plant’s multifaceted biological activity is attributed to the presence of monoterpenes, such as citronellol and geraniol, as well as non-volatile polyphenolic fractions and organic acids. Research has demonstrated the efficacy of PGEO (P. graveolens essential oil) in mitigating inflammation, a phenomenon attributable to the suppression of NF-κB and MAPK signaling pathways, as well as the inhibition of inflammatory mediators such as histamine, prostaglandins (PGs), and nitric oxide (NO). Furthermore, a broad spectrum of antimicrobial activity has been demonstrated against pathogens such as MRSA and Mycobacterium tuberculosis, whilst myricetin derivatives have been shown to enable the effective eradication of bacterial biofilms. It is also noteworthy that the oil’s components can reduce ACE2 receptor expression, indicating their potential to inhibit SARS-CoV-2 infection. Active compounds, such as geraniol, have been shown to modulate metabolic processes through interaction with LXR and FXR nuclear receptors. In addition, these compounds have been observed to exhibit spasmolytic effects within the gastrointestinal tract by blocking calcium channels. The influence on the HPA axis and the GABAergic system provides a scientific rationale for the plant’s traditional use in reducing stress and anxiety. Nevertheless, variations in chemical composition, determined by geographical origin, and an insufficient number of rigorous clinical data hinder the full medical implementation of this plant. It is imperative that further standardization of extracts and their verification in clinical trials is undertaken. 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

Background: Respiratory tract infections (RTIs) and urinary tract infections (UTIs) are among the most common infections in humans. It is estimated that millions of deaths occur each year worldwide due to these infections. Pseudomonas aeruginosa (P. aeruginosa), in particular, represents a public health threat since it has a high ability to acquire resistance to different antibiotic classes. The aim of this study was to determine the prevalence and antimicrobial resistance patterns of P. aeruginosa isolates from patients with RTIs and UTIs in Lebanon. Methods: This retrospective study was performed during 2020–2022 and 2024–2025. Samples were collected from both inpatients and outpatients, where identification and isolation of bacteria were performed along with antibiotic susceptibility testing. Results: The overall prevalence of P. aeruginosa isolates in RTI cases over the study period was 10.9%, and that of UTI cases was 1.3%. The general antimicrobial resistance profile of P. aeruginosa isolates from RTI and UTI cases showed the highest resistance for Piperacillin–Tazobactam and Aztreonam, respectively. For RTIs, antibiotic resistance decreased from 48.1% in 2020 to 36.7% in 2025 and increased from 16.7% to 19.4% for UTIs. Conclusions: According to our research, P. aeruginosa with low antibiotic susceptibility is frequently found in isolated samples, highlighting the significant challenge in treating severe infectious illnesses. To choose focused and efficient antibiotic therapy for RTIs and UTIs and to stop the emergence of multidrug-resistant (MDR) bacteria, it is essential to accurately identify the pathogenic microorganisms and their antibiotic susceptibility patterns. 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

Bovine alphaherpesvirus 1 (BoHV-1) acute infection induces respiratory tract disorders and conjunctivitis and suppresses immune responses that may cause bacterial pneumonia. BoHV-1 infection establishes lifelong latency in sensory neurons in trigeminal ganglia (TG), the central nervous system, and certain cells in the pharyngeal tonsil. BoHV-1 is a chronic problem in the cattle industry because stress, including the synthetic corticosteroid dexamethasone, triggers reactivation from latency after an intravenous injection. The BoHV-1 immediate early transcription unit 1 (IEtu1) promoter drives expression of infected cell protein 0 (bICP0) and bICP4, two viral transcriptional regulators. Stress activates the glucocorticoid receptor (GR), and Krüppel-like factor 15 (KLF15) cooperatively transactivates the BoHV-1 IEtu1 promoter if both GR response elements (GREs) are intact. Since the bICP0 gene contains a separate early (E) promoter, we tested the hypothesis that GR+KLF family members transactivate the bICP0 E-promoter. GR+KLF4, both pioneer transcription factors, cooperatively stimulate bICP0 E-promoter activity in mouse neuroblastoma cells (Neuro-2A), and stimulate productive infection. Notably, the bICP0 E-promoter lacks GREs, suggesting that a novel mechanism triggers transactivation. CA motifs and C-rich Sp1 binding sites in bICP0 E-promoter sequences are crucial for transactivation and binding to GR and KLF4. Full article

Although most upper respiratory tract infections (URTIs) have a viral etiology, antibiotics are widely prescribed, thus contributing substantially to antimicrobial resistance. This study investigated the potential beneficial effects of a novel strain, Limosilactobacillus reuteri LMG P-27481, against major URT pathobionts (Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae) with the aim of reducing or delaying antibiotic use. Antibacterial and immunomodulatory activities were evaluated using L. reuteri alone or combined with resveratrol, a natural compound with antiviral and anti-inflammatory properties. Both agents inhibited pathogen growth, while their combination showed additive antibacterial activity, particularly against Gram-negative bacteria. Antioxidant assays demonstrated significant antioxidant capacity for both agents, with enhanced effects in combination in NBT and ABTS assays but antagonistic in ORAC. Immune mediators (IL-6, IL-8, IL-1β, TNF-α, IL-25, IL-33, CCL17, CCL22) were assessed in epidermal, epithelial, and macrophage cell lines, together with epidermal integrity markers (Filaggrin, Loricrin, Involucrin) in a 3D reconstructed human skin model (EpiDermFT^TM). L. reuteri, resveratrol, and their combination exerted cell-specific effects in the different models, modulating cytokine expression and production, and barrier integrity. Our findings support the potential efficacy of oral L. reuteri LMG P-27481 plus resveratrol in URTIs. 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