Search Results (545)

Background/Objectives: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia, and the increasing prevalence of macrolide-resistant M. pneumoniae (MRMP) has created a need for rapid assays that simultaneously detect the pathogen and resistance-associated mutations. This study developed and validated a fully automated laboratory-developed test (LDT) using the Hologic Panther Fusion^® system. Methods: The automated MP assay targeting domain V of the 23S rRNA gene was implemented on the Panther Fusion^® platform. Analytical performance was evaluated by determining the limit of detection (LoD), repeatability, reproducibility, and cross-reactivity. Clinical performance was assessed using 419 nasopharyngeal swab specimens (90 positive and 329 negative) and compared with conventional real-time PCR. Mutation status was confirmed by sequencing. Results: The automated MP assay detected wild-type, A2063G, and A2064G targets with an LoD of approximately 1 × 10² copies/μL and showed no cross-reactivity with 16 respiratory pathogens. Clinical sensitivity and specificity were 96.7% (87/90) and 100% (329/329), respectively, with high concordance with conventional real-time PCR and sequencing. Conclusions: The automated MP assay provides rapid and accurate detection of M. pneumoniae and major macrolide resistance mutations, offering a practical molecular diagnostic solution for routine clinical laboratories. Full article

Background: Antimicrobial resistance is a major global health challenge, with multidrug-resistant organisms (MDROs) emerging faster than new antimicrobial agents are being developed. The epidemiology of MDROs varies substantially across healthcare settings; however, newly established hospitals remain understudied. This study aimed to characterise the epidemiology and temporal trends of MDROs in a newly established tertiary hospital. Methods: A five-year retrospective longitudinal surveillance study was conducted from 2019 to 2023 in a newly established tertiary hospital in Southern China. Clinical isolates were collected from intensive care unit (ICU) and non-ICU wards. Nine major MDROs were investigated, including extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) and Escherichia coli (ESBL-ECO); carbapenem-resistant Klebsiella pneumoniae (CRKP), Escherichia coli (CRECO), Acinetobacter baumannii (CRAB), and Pseudomonas aeruginosa (CRPA); methicillin-resistant Staphylococcus aureus (MRSA); and vancomycin-resistant Enterococcus faecium (VREfm) and Enterococcus faecalis (VREfa). Results: A total of 1533 MDRO isolates were identified during the study period. The predominant pathogens were ESBL-ECO (48.1%), ESBL-KP (16.4%), MRSA (11.4%), and CRPA (11.1%). Most isolates were recovered from non-ICU wards (85.4%), and more than half (51.5%) were community-onset. Isolation rates of ESBL-ECO, CRECO, CRAB, and CRPA were significantly higher in the ICU than in non-ICU wards (all p < 0.05). The incidence density rate of hospital-acquired infections caused by ESBL-KP, CRAB, and CRPA was also significantly higher in the ICU (all p < 0.05). Longitudinal analysis revealed divergent trends among MDROs. While most MDRO isolation rates remained below provincial and national benchmark levels, CRKP and CRAB showed significant increasing trends. CRPA exhibited a distinct pattern, increasing rapidly during the early years after hospital opening, exceeding both provincial and national benchmarks by the second year and remaining elevated thereafter. Conclusions: MDRO epidemiology during the first five complete calendar years after hospital opening was characterised by a predominance of ESBL-ECO, ESBL-KP, MRSA, and CRPA, together with substantial non-ICU and community-onset burdens and heterogeneous temporal patterns across organisms. CRPA increased rapidly and remained above the available external benchmark thereafter. These findings highlight the need for hospital-wide, organism-specific MDRO surveillance, while maintaining intensified infection prevention and control in ICUs and continued vigilance for carbapenem-resistant pathogens, particularly CRPA. Full article

Background: Legionella pneumophila is a leading cause of community- and hospital-acquired pneumonia (HAP/CAP), although the clinical and radiological features associated with infection remain incompletely defined. This study aimed to identify clinical, comorbidity-related, and chest computed tomography (CT) features associated with L. pneumophila pneumonia in hospitalized adults with community-acquired pneumonia (CAP). Methods: A retrospective case–control study was conducted at a tertiary-care university hospital in Italy between January 2019 and August 2025. Eighty patients positive for L. pneumophila were compared with 79 controls negative for L. pneumophila. Demographic, clinical, microbiological, and radiological data were collected, and factors independently associated with infection were evaluated using multivariable logistic regression analysis. Results: Patients with L. pneumophila infection exhibited a greater comorbidity burden, particularly heart failure, and were more frequently smokers. Bilateral lung involvement and hilar/mediastinal lymphadenopathy were significantly more common among Legionella-positive patients, whereas overall pulmonary complications and bilateral pleural effusion were more frequently observed in controls. Multivariable analysis identified comorbidity burden as an independent positive predictor of L. pneumophila infection, while intensive care unit admission, oxygen therapy, and pulmonary complication score were independently associated with a lower likelihood of infection. Conclusions: The integration of comorbidity assessment with readily available chest CT findings may help raise clinical suspicion of L. pneumophila pneumonia and support consideration of appropriate diagnostic testing. Full article

Background and Objectives: Urinary tract infections are common in clinical practice, but in hospital settings, especially among older and catheterized patients, the microbial ecology and resistance burden may differ substantially from community-acquired infections. Local surveillance is therefore essential to support appropriate empirical treatment and antimicrobial stewardship. The objective is to describe the microbiological epidemiology of urinary isolates in a tertiary hospital and evaluate temporal trends in antimicrobial resistance among the most frequently isolated microorganisms. Materials and Methods: This retrospective observational study analyzed microbiology laboratory data from Tor Vergata University Hospital, Rome, Italy, collected from January 2022 to June 2025. After WHONET-based deduplication using a 30-day repeat-isolate rule, 5788 deduplicated urinary isolates and 85,888 microorganism–drug associations were included. Descriptive analyses, cumulative antibiograms/antimycograms, and quarterly resistance trends were assessed using univariable and multivariable regression analyses. Results: The population was predominantly elderly, inpatient, and catheter-exposed. Gram-negative organisms predominated, followed by Gram-positive bacteria and fungi. The most frequent isolates were E. coli, K. pneumoniae, E. faecalis, and C. albicans. Although microorganism distribution remained broadly stable over time, resistance increased in several clinically relevant organism–drug combinations, especially among major Enterobacterales. Conclusions: In this high-complexity hospital population, urinary isolates showed a relatively stable microorganism distribution but progressive changes in susceptibility among selected urinary isolates. These findings support setting-specific microbiological surveillance and stewardship-informed empirical treatment strategies. Full article

Background: Legionella pneumophila is a rare but severe cause of community-acquired pneumonia and can lead to acute respiratory distress syndrome (ARDS). Awake prone positioning (APP) has been recognized as an effective adjunct for non-intubated patients with hypoxemic respiratory failure, primarily studied in coronavirus disease 2019 (COVID-19) and other ARDS etiologies. Its application in Legionella-associated ARDS remains poorly documented. Therefore, in this work, we present a case of Legionella-associated ARDS successfully managed with APP, high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), levofloxacin, and corticosteroids. Case presentation: A 62-year-old male with multiple comorbidities, including type 2 diabetes mellitus (T2DM) and a history of coronary artery bypass surgery, presented with a 3-day history of productive cough, exertional dyspnea, and general malaise. Oxygen saturation on admission was 90%, with fever and tachycardia. Inflammatory markers were markedly elevated. Chest computed tomography (CT) revealed extensive bilateral pulmonary infiltrates. Despite a negative urinary Legionella antigen test, sputum polymerase chain reaction (PCR) confirmed Legionella pneumophila on day 2. A Horowitz index of 147 mmHg on day 2 established moderate ARDS. The patient was treated with HFNC oxygen therapy, NIV, and APP for up to 12 h daily. Antibiotic therapy was initiated with amoxicillin/clavulanic acid and clarithromycin, subsequently streamlined to levofloxacin upon microbiological confirmation. Methylprednisolone 40 mg/day was administered for 8 days as adjunctive ARDS therapy. The patient demonstrated gradual clinical and respiratory improvement without requiring endotracheal intubation. Follow-up chest CT on day 7 showed regression of bilateral consolidations and ground-glass opacities (GGOs). The patient was transferred to pulmonary rehabilitation on day 11 and completed antibiotic therapy as an outpatient. Conclusions: This case illustrates the successful use of APP combined with HFNC and NIV alongside standard medical therapies, including appropriate antibiotics and corticosteroids, to avoid intubation in moderate ARDS secondary to Legionella pneumonia. Early initiation of APP may be a valuable strategy in Legionella-associated ARDS in carefully selected patients. Full article

Klebsiella pneumoniae (K. pneumoniae) is a leading cause of hospital- and community-acquired lower respiratory infections (LRI). The emergence of antimicrobial resistance (AMR), especially carbapenem-resistant strains (CRKP), poses a serious global health threat. Using Global Burden of Disease (GBD) 2021 data, we estimated AMR-related mortality for K. pneumoniae-associated LRI across regions from 1990 to 2021. Joinpoint regression analysis identified temporal trends. Global mortality declined overall, with a 70% reduction in under-5 deaths but a doubling among adults over 70 years. Deaths associated with and attributable to AMR decreased by 18.9% and 4.5%, respectively. The age-standardized mortality rate (ASMR) fell by nearly 50%. In contrast, the mortality burden associated with carbapenem resistance increased markedly, with AMR-associated deaths rising by 157% and disproportionately affecting high-burden regions such as Sub-Saharan Africa and South Asia. Despite overall progress, the increasing mortality burden associated with carbapenem resistance in K. pneumoniae-associated LRI poses a critical and persistent global health threat. Full article

Klebsiella pneumoniae (K. pneumoniae) is a major opportunistic pathogen associated with a broad spectrum of hospital-and community-acquired infections. Biofilm formation contributes to bacterial persistence, stress tolerance, and host immune clearance. In this study, we constructed a transposon mutant library of the clinical K. pneumoniae strain KP20 using a mariner-based mutagenesis system and screened for mutants exhibiting defective biofilm formation. Targeted knockout of thrA significantly reduced biofilm formation and attenuated the adhesion and invasion of K. pneumoniae with respect to human airway epithelial Calu-3 cells and lung adenocarcinoma A549 cells. These phenotypic changes are associated with altered transcription of the gene clusters responsible for type I and type III fimbria biosynthesis. Moreover, deletion of thrA compromised bacterial tolerance to acidic and alkaline stresses and increased susceptibility to phagocytosis by dendritic cells. In a murine infection model, thrA deletion significantly attenuated the virulence of K. pneumoniae and decreased bacterial colonization in target organs. Collectively, these findings indicate that thrA substantially contributes to biofilm formation, pH stress tolerance, host–cell interaction, and virulence in K. pneumoniae. Full article

Background: Community-acquired pneumonia (CAP) remains a leading cause of pediatric morbidity and mortality worldwide, particularly in low-resource settings. Although antimicrobial therapy is the cornerstone of treatment, disease severity is often influenced not only by pathogen burden but also by dysregulated host inflammation. Systemic corticosteroids have therefore been investigated as adjunctive agents to reduce inflammation-mediated lung injury, but their role in children remains controversial. Methods: This narrative review summarizes current evidence on systemic corticosteroid use in pediatric pneumonia. The review focuses on biological mechanisms, clinical indications, patient selection, therapeutic regimens, timing and duration of therapy, clinical outcomes, and safety. Particular attention is given to severe CAP, Mycoplasma pneumoniae pneumonia, complicated pneumonia with parapneumonic effusion or empyema, viral pneumonia, wheezing-associated phenotypes, and immunocompromised children. Results: Available evidence suggests that corticosteroids may provide benefit in selected pediatric phenotypes characterized by severe inflammation, respiratory compromise, refractory disease, or airway hyperreactivity. Reported benefits include faster fever resolution, reduction in inflammatory markers, shorter hospital stay, more rapid clinical stabilization, and improved radiographic recovery, particularly in severe or refractory Mycoplasma pneumoniae pneumonia and selected complicated cases. However, findings are inconsistent, and treatment effects appear strongly dependent on etiology, disease severity, timing of administration, corticosteroid regimen, and patient phenotype. Routine use in uncomplicated CAP or unselected pediatric populations is not supported. Potential adverse effects include hyperglycemia, gastrointestinal and neurobehavioral symptoms, sleep disturbance, immunosuppression with an increased risk of secondary infection, delayed viral clearance in selected viral infections, and possible masking of inadequate anti-infective response or evolving complications. Conclusions: Current evidence supports a cautious, individualized, phenotype-driven approach to corticosteroid therapy in pediatric CAP. Well-designed pediatric randomized controlled trials are needed to define precise indications, optimal regimens, timing, and long-term safety. Full article

Background: Pediatric pleural empyema is a major complication of community-acquired pneumonia and remains associated with substantial morbidity despite advances in vaccination, antimicrobial therapy, and supportive care. Intrapleural fibrinolytic therapy has become an important minimally invasive treatment for complicated parapneumonic effusions and empyema, but uncertainty persists regarding the optimal fibrinolytic agent, treatment protocols, patient selection, and indications for surgical intervention. Methods: A narrative review of the literature was conducted to summarize current evidence on the use of intrapleural fibrinolytic therapy in pediatric pleural empyema. Experimental studies, randomized controlled trials, observational studies, systematic reviews, meta-analyses, and international clinical practice guidelines were critically reviewed. Particular attention was paid to the biological rationale for fibrinolysis, pharmacological characteristics of available agents, comparative effectiveness with video-assisted thoracoscopic surgery (VATS), practical treatment protocols, safety, and future research priorities. Results: Intrapleural fibrinolysis effectively improves pleural drainage by lysing fibrin septations during the fibrinopurulent stage of empyema and is associated with shorter hospitalization compared with chest-tube drainage alone. Urokinase remains the fibrinolytic agent supported by the highest-quality pediatric randomized evidence, whereas alteplase has demonstrated favorable outcomes in observational studies and randomized comparisons with VATS. Current evidence indicates comparable clinical outcomes between fibrinolysis and primary VATS in appropriately selected children, although fibrinolysis is generally associated with lower treatment costs and avoidance of surgery in most patients. Conventional-dose fibrinolytic therapy has an acceptable safety profile, with clinically significant bleeding reported only rarely. Current pediatric evidence does not support the routine addition of DNase to tissue plasminogen activator. Conclusions: Intrapleural fibrinolytic therapy represents a safe, effective, and minimally invasive first-line treatment for most children with complicated parapneumonic effusions and pleural empyema requiring drainage. Management should be individualized within a multidisciplinary framework, integrating timely diagnosis, image-guided pleural drainage, appropriate antimicrobial therapy, and selective surgical intervention. Future multicenter studies are needed to optimize fibrinolytic protocols, validate predictive biomarkers, and further standardize clinical management. Full article

Streptococcus pneumoniae is the major causative agent of community-acquired pneumonia, one of the main infectious diseases that causes inflammation in the alveoli and leads to significant morbidity and mortality across various age groups. Current treatments are challenged by multidrug-resistant strains of S. pneumoniae, which has led to the reemergence of pneumonia in recent years; therefore, it is pivotal to identify new drug targets. The enzyme chorismate synthase (CS), involved in the shikimate pathway of S. pneumoniae, aids in the synthesis of vital aromatic amino acids and other metabolites required for bacterial viability. The present study identifies natural compounds that can inhibit CS using an in silico approach, including pharmacophore modeling, virtual screening, molecular docking, ADME analysis, and molecular dynamics (MD) simulations. Our results suggest that the identified compounds can bind effectively to the active site of S. pneumoniae CS (SpCS), exhibiting affinities better than the known inhibitor 1-benzofuran-3-one and close to the enzyme’s natural substrate, 5-enolpyruvylshikimate-3-phosphate (EPSP). This study suggests lead natural compounds as promising candidates for further investigation as potential inhibitors for the treatment of pneumonia, offering a novel strategy to combat this resilient pathogen. Full article

Background/Objective: To externally validate our previously published machine learning model for identifying hospitalized patients with community-acquired pneumonia (CAP) at low risk of respiratory deterioration or death using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Methods: This is a retrospective cohort study of adult patients (≥18 years) who were admitted with CAP and acute hypoxemic respiratory failure using the publicly available MIMIC-IV critical care dataset (Beth Israel Deaconess Medical Center, Boston, MA). We conducted an external validation study of a previously developed gradient boosting machine (GBM) model without recalibration using data available within the first 6 h of hospital admission. Results: For the primary composite outcome (need for advanced respiratory support [high flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV)] or in-hospital death), the gradient boosting model demonstrated comparable performance in the derivation and external validation cohorts. The area under the receiver operating characteristic curve (AUC) was 0.713 in the Mayo cohort (n = 4379) and 0.689 in the MIMIC-IV cohort. Accuracy was 0.612 (95% confidence interval [CI], 0.595–0.628) versus 0.606 (95% CI 0.600–0.611), specificity 0.574 versus 0.523, sensitivity 0.723 versus 0.754, NPV 0.860 versus 0.842, and PPV 0.364 versus 0.401, respectively. For secondary outcomes, model discrimination was comparable between cohorts. The AUC for in-hospital mortality was 0.727 in the Mayo Cohort versus 0.733 in MIMIC-IV; for IMV, 0.736 versus 0.724; and for NIMV, 0.732 versus 0.708. Conclusions: Our machine learning algorithm demonstrated good discrimination and a high negative predictive value for identifying low-risk hospitalized CAP patients for respiratory deterioration or death in the external MIMIC-IV dataset, supporting its potential utility for prognostic enrichment in pneumonia clinical trials. Full article

Enterobacteriaceae are a diverse family of Gram-negative, rod-shaped, facultatively anaerobic bacteria that serve as important indicators of food safety. Many species within this family, including common foodborne pathogens, are major contributors to both community- and hospital-acquired infections. The widespread use of antibiotics in agriculture has facilitated the emergence and dissemination of antimicrobial-resistant bacteria in food products, livestock, and the environment. This study investigated the prevalence and genomic characteristics of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae isolated from food sources in Saudi Arabia. A total of 160 isolates preserved in the Saudi Food and Drug Authority (SFDA) biobank were screened for antimicrobial resistance using indicator β-lactam antibiotics according to CLSI guidelines. Phenotypic screening indicated that Escherichia coli O145, E. coli O157, Klebsiella pneumoniae, and Cronobacter sakazakii isolates were not ESBL producers. In contrast, ESBL production was detected among Salmonella spp. isolates, and 13 confirmed ESBL-producing Salmonella isolates were subsequently subjected to whole-genome sequencing (WGS). Genomic analysis identified the ESBL gene blaCTX-M-65, along with multiple antimicrobial resistance determinants, virulence-associated genes, and plasmid replicons, predominantly belonging to the IncFIB and IncX families. These findings provide important insights into the occurrence of ESBL-producing Enterobacteriaceae in food sources and highlight the value of integrating phenotypic and genomic approaches for antimicrobial resistance surveillance within food safety systems. Full article

Background/Objectives: 23-valent pneumococcal polysaccharide vaccine (PPV23) effectiveness against community-acquired pneumonia (CAP) remains controversial, with critical gaps in low-coverage settings and beyond 5 years post-vaccination. We estimated real-world PPV23 effectiveness against CAP hospitalization and characterized its duration among elderly adults in a low-coverage region. Methods: A multicenter matched case–control study was conducted across 14 hospitals in Eastern China (2018–2022). Cases were patients aged ≥60 years hospitalized with clinically diagnosed CAP. Up to three controls per case were matched on sex, age (±3 years), admission date (±5 days), hospital, and residential community. Conditional logistic regression estimated vaccine effectiveness (VE), adjusting for chronic comorbidities and healthcare utilization. Results: Among 6645 cases and 15,806 controls, 5-year PPV23 coverage was 2.14% (cases) and 2.76% (controls). PPV23 was associated with a 22.5% reduction in CAP hospitalization (adjusted VE = 22.5%, 95% CI: 4.1% to 37.3%). Protection was concentrated in non-severe CAP (adjusted VE = 25.7%, 95% CI: 7.0% to 40.7%), with no significant effect in severe CAP (adjusted VE = −11.7%, 95% CI: −115.1% to 42.0%). Extending the exposure window to 6 years yielded no significant VE (adjusted VE = 17.3%, 95% CI: −1.8% to 32.8%). Conclusions: PPV23 provides meaningful protection against CAP hospitalization in elderly adults in low-coverage settings, only for non-severe disease. Waning efficacy beyond 5 years supports revaccination at that interval. Full article

Community-acquired pneumonia is one of the main causes of morbidity and mortality due to infections worldwide. This has led to the study of the use of corticosteroids as adjunctive therapy, which has shown an inclination to provide clinical benefits. However, controversy persists regarding the use of one corticosteroid over another Objectives: Evaluate the outcomes associated with the use of hydrocortisone versus methylprednisolone in patients with community-acquired pneumonia. Methods: We conducted a multicenter retrospective cohort study that included hospitalized adults diagnosed with CAP at two high-complexity clinics in Colombia between 2010 and 2020. Propensity score matching was used in a 1:1 ratio to balance the baseline characteristics between the hydrocortisone and methylprednisolone groups. The primary outcome was 30-day mortality. Secondary outcomes included septic shock, vasopressor use, admission to the intensive care unit, mechanical ventilation, and other hospital outcomes. Survival analyses were performed using Kaplan–Meier curves and estimates of the average treatment effect, as well as subgroup analyses according to the dose and duration of treatment. Results: The study initially included 366 patients, with significant baseline differences between groups. After matching, an adjusted cohort of 168 patients (84 per group) was obtained, with an adequate balance of clinical, paraclinical, and severity-related variables. No statistically significant differences were found in 30-day mortality between patients who received hydrocortisone and those who received methylprednisolone before or after matching. Additionally, no differences were detected in the secondary clinical outcomes. Survival analyses revealed no differences according to corticosteroid type, treatment duration, or administered dose. Conclusions: In this retrospective propensity-score-matched cohort study, no differences were observed in 30-day mortality or other clinical outcomes between hydrocortisone and methylprednisolone in patients with community-acquired pneumonia. Full article

Background/Objectives: Community-acquired pneumonia (CAP) is a leading cause of ICU admission and death in older adults, yet the severity scores used in this setting were not developed for, or validated in, older intensive care patients. We compared a pneumonia-specific score (SMART-COP) with the general ICU scores SOFA and APACHE II and with CURB-65 for predicting adverse outcomes in this population. Methods: In this single-center prospective observational study, 227 consecutive patients aged ≥65 years admitted to the ICU with CAP were enrolled. SMART-COP and CURB-65 were calculated at hospital admission and SOFA and APACHE II at ICU admission. The discrimination of each score for four outcomes—in-ICU mortality, need for intubation, vasopressor requirement, and hospital-acquired pneumonia (HAP)—was assessed by ROC analysis, and areas under the curve (AUCs) were compared pairwise using the DeLong test. Results: All four scores predicted mortality, intubation, and vasopressor requirement (all p ≤ 0.001), but none discriminated well for HAP (all AUCs < 0.70). SMART-COP had the highest AUCs for mortality (0.846) and intubation (0.870), significantly exceeding CURB-65 (both p < 0.01) while performing comparably to SOFA and APACHE II. SOFA was the strongest predictor of vasopressor requirement (AUC: 0.867). Conclusions: In older ICU patients with CAP, SMART-COP—calculable from routine parameters at admission—matched far more complex ICU scores for mortality and intubation and outperformed CURB-65. The optimal score depends on the outcome of interest. Full article