Search Results (520)

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant pathogen for both hospital-acquired and community-acquired infections, characterized by its strong epidemic potential and high mortality rate, posing a severe threat to global public health. CRKP spreads widely across the globe through the horizontal transfer of plasmid-mediated resistance genes such as *blaKPC*, *blaNDM*, and *blaOXA-48*. The clinical treatment options for this bacterium are limited, and its resistance has been increasing year by year, urgently necessitating the development of new antimicrobial drugs or alternative strategies. In recent years, the CRISPR-Cas system has shown great potential in the diagnosis and treatment of CRKP, including rapid detection and identification, gene editing, antimicrobial strategies, and resistance inhibition. For instance, CRISPR-Cas12a/13a can be used for the rapid detection and identification of CRKP, while CRISPR-Cas9/Cas3 can target resistance genes to reverse the resistance of strains. With the advancement of delivery and biotechnologies, the CRISPR-Cas system is expected to become an important tool against drug-resistant CRKP. This review focuses on the application of the CRISPR-Cas system in the detection and treatment of CRKP, analyzing its technical advantages, limitations, and future development directions. Full article

Background/Objectives: Patients in long-term care hospitals (LTCHs) are at increased risk of harboring antimicrobial-resistant organisms due to frequent healthcare exposure and multiple comorbidities. This retrospective observational study aimed to compare the antimicrobial susceptibility of bacterial isolates from LTCH-onset infections (LTCHIs) with those from community-acquired infections (CAIs) in elderly patients. Methods: This study was conducted at a 700-bed urban tertiary university hospital and included patients aged ≥65 years with positive cultures for bacteremia, lower respiratory tract infections (LRTIs), or urinary tract infections (UTIs) within 48 h of admission. Medical records, including antimicrobial susceptibility test results, were reviewed for a total of 1780 patients and their isolates. Antimicrobial susceptibility patterns were compared between LTCHI and CAI patients. Results: Patients with LTCHI exhibited significantly higher antimicrobial non-susceptibility than those with CAIs across multiple pathogens and antimicrobial classes (p < 0.05). In bacteremia, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae from LTCHI cases showed increased non-susceptibility to β-lactams and fluoroquinolones. In LRTIs, Pseudomonas aeruginosa and Acinetobacter baumannii demonstrated high non-susceptibility to carbapenems (52.9% and 90%, respectively) and aminoglycosides. In UTIs, LTCHI isolates exhibited broader resistance among Enterobacterales and P. aeruginosa. Notably, the proportion of multidrug-resistant organisms, including carbapenem-resistant Enterobacterales (15.4–50.0%) and carbapenem-resistant Acinetobacter baumannii (90.5%), was substantially higher in the LTCHI group across all infection sites. Conclusions: Elderly patients with LTCHI are more likely to harbor antimicrobial-resistant pathogens than those with CAIs. Careful consideration of LTCHI origin is therefore essential for empirical antibiotic selection and for strategies aimed at limiting further resistance. Full article

Pseudomonas fluorescens is a rare, environmental Gram-negative bacterium that has been rarely reported as a cause of respiratory tract infections. This paper presents a case of a 72-year-old male who developed community-acquired pneumonia due to P. fluorescens. The diagnosis was made by sputum culture and he responded to meropenem treatment. A literature search revealed three previously reported cases of P. fluorescens pneumonia. These cases primarily affected elderly male patients. All reported patients demonstrated positive clinical outcomes following appropriate antimicrobial therapy. This case highlights that although P. fluorescens is often considered a colonizer, it may act as a potential pathogen in selected clinical settings. Full article

Complicated community-acquired pneumonia (cCAP) remains a major cause of morbidity in children. Although pneumococcal conjugate vaccines (PCVs) have reduced invasive disease, severe complications such as empyema and lung abscess persist. A retrospective analysis was conducted on 69 children treated at the University Children’s Hospital Belgrade between 2019 and 2024. Data included demographic characteristics, pneumococcal vaccination status, and radiologically confirmed complications. Patients were classified by residence and vaccination status. Statistical analysis included chi-square (χ²) tests, odds ratios (ORs) with 95% confidence intervals, and multivariable logistic regression. Pleuropneumonia and pleural effusion were the most frequent complications, while empyema and lung abscess were the most severe. Both occurred significantly more often in unvaccinated children (p = 0.0054 and p = 0.0027). Multivariable analysis confirmed vaccination as an independent protective factor against empyema (adjusted OR = 0.19, 95% CI 0.06–0.61). No significant regional differences were observed after accounting for vaccination status. Vaccination showed a strong protective effect against empyema and lung abscess (OR = 0.24 and 0.04, respectively). Unvaccinated children had significantly longer hospital stays, indicating a more severe clinical course. Prolonged hospitalization was associated with intensified antibiotic therapy, reflecting underlying disease severity. Lack of pneumococcal vaccination is strongly associated with severe complications in children with cCAP. Maintaining high PCV coverage remains essential, alongside early recognition and timely management of pleural disease. Full article

In this work, we propose ARTEMIS, a novel and highly interpretable deep learning pipeline for the automatic classification of Chest X-ray (CXR) and Computed Tomography (CT) images into different categories related to important clinical outcomes: COVID-19 infection, Community-Acquired Pneumonia (CAP) cases, and Normal cases. Unlike existing models based on the static feature enhancement step, ARTEMIS proposes a learnable preprocessing component that dynamically adapts the image contrast and sharpness in training mode, facilitating adaptive optimization. Our hybrid network combines EfficientNet-B0 backbone with built-in SE attention with the optional lightweight Transformer encoder block to jointly learn local radiological features and global relationships between pixels. Comprehensive experiments have been conducted on five different datasets, which comprise four publicly available ones and one novel CT dataset annotated by radiologists, including X-ray and CT modalities. Experimental results show strong robustness and generalization with macro F1-scores greater than 96% on public datasets and 99.39% accuracy on our new CT dataset. To interpret the decision-making process, Grad-CAM++ is employed to generate class-discriminative saliency maps; the highlighted regions are systematically validated against established radiological criteria by a board-certified radiologist, confirming that model decisions are grounded in clinically meaningful pulmonary findings rather than imaging artifacts. Full article

Background/Objectives: In Europe, Pseudomonas aeruginosa is the second most common cause of ventilator-associated pneumonia in intensive care units. Intrinsic antibiotic resistance and acquired carbapenemases can lead to high mortality. To guide more targeted antimicrobial therapy and adequate infection control measures, we performed a multicenter study on the prevalence and genetic basis of carbapenem resistance among P. aeruginosa (CR-PA) across 17 community hospitals in Austria. Methods: During a 3-month period, we collected 621 P. aeruginosa isolates from 560 patients. Antibiotic susceptibility testing was performed according to EUCAST guidelines, and all CR-PA isolates were subjected to whole genome sequencing. Results: Antibiotic susceptibility testing revealed carbapenem resistance in 5.41% (36/621) of the investigated P. aeruginosa isolates. Only 3 produced a carbapenemase (2 Verona Integron-encoded Metallo- ß-lactamases and 1 Imipenemase Metallo-ß-lactamase) and carried a carbapenemase-encoding gene. Among the studied P. aeruginosa isolates there was a high genetic diversity, excluding a single driving epidemic lineage in the included Austrian hospitals. Conclusions: The absence of interhospital clonal dominance suggests that carbapenem resistance emerged independently in different centers, likely driven by local antibiotic selection pressures rather than regional clonal spread. Full article

Klebsiella pneumoniae is an opportunistic pathogen associated with both community-acquired and nosocomial infections. Multidrug-resistant (MDR) strains are increasingly implicated in urinary tract infections (UTIs), traveller’s diarrhoea, bacteraemia, and sepsis. β-lactam antibiotics are commonly used for treatment; however, antimicrobial resistance has emerged largely due to the production of extended-spectrum β-lactamases (ESBLs), which confer resistance mainly to penicillins, oxyimino-cephalosporins, and monobactams, while cephamycins and carbapenems usually remain stable to ESBL-mediated hydrolysis and compromise therapeutic efficacy. ESBL-producing strains represent a major cause of severe Gram-negative infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae among UTI patients in Jordanian hospitals (Al Mafraq, Ma’an, and Islamic Hospitals), evaluate their antimicrobial susceptibility patterns, and detect antimicrobial resistance genes at the molecular level. A total of 450 urine isolates of K. pneumoniae were collected from UTI patients between November 2023 and May 2024. Isolates were identified in hospital laboratories using standard microbiological methods. Antimicrobial susceptibility testing was performed, and molecular characterisation of ESBL-associated genes was conducted using polymerase chain reaction (PCR). Out of 450 K. pneumoniae isolates collected from UTI patients across three Jordanian regions, 72 (16%) were confirmed as ESBL producers. Among the 72 ESBL-positive K. pneumoniae isolates, 34 (47.2%) were recovered from the Central region, 20 (27.8%) from the North, and 18 (25.0%) from the South. Molecular analysis revealed that 41.7% of ESBL-producing isolates carried the blaCTX-M gene, while 33.3% harboured the blaOXA gene. All ESBL-producing isolates demonstrated antimicrobial resistance to third-generation cephalosporins. A significantly higher proportion of ESBL-producing isolates was identified in female patients (84.7%) compared with males (15.3%). A significant association was observed between blaOXA gene distribution and geographic region (p = 0.016), whereas blaCTX-M gene distribution showed no significant regional association. ESBL-producing K. pneumoniae accounted for a substantial proportion of UTI isolates in Jordan, with blaCTX-M identified as the predominant resistance gene. The higher burden observed in the Central region and among female patients highlights notable distribution patterns in this cohort. These findings emphasise the necessity for sustained molecular surveillance and strengthened antimicrobial stewardship strategies to limit the dissemination of ESBL-producing strains in Jordanian healthcare settings. Full article

Background/Objectives: Community-acquired pneumonia (CAP) is a leading cause of mortality in older adults. Traditional prognostic scores may underestimate risk in frail patients by assuming linear relationships between predictors and outcomes. This study aimed to develop and validate explainable machine learning models integrating the administrative Hospital Frailty Risk Score (HFRS) to predict in-hospital mortality in a nationwide cohort of older adults in Chile. Methods: A retrospective cohort study was conducted using anonymized hospital discharge records from the Chilean National Health Fund (FONASA), including 58,306 hospitalization episodes of adults aged ≥60 years across 72 public hospitals. Fourteen supervised machine learning algorithms were trained using five routinely collected predictors: age, sex, HFRS, Charlson Comorbidity Index, and length of stay. Model performance was evaluated on an independent test set using AUC-ROC. SHAP (SHapley Additive exPlanations) values were calculated to assess global and individual predictor contributions. Results: The Extra Trees classifier achieved the highest discriminative performance (AUC-ROC 0.862), outperforming logistic regression (0.642) and other linear models. SHAP analyses identified HFRS as the most influential predictor (mean |SHAP| = 0.66), followed by length of stay, age, and comorbidities. Conclusions: Ensemble tree-based models incorporating administrative frailty measures provide superior mortality prediction compared to traditional linear approaches. Frailty emerged as the primary driver of risk, supporting scalable early stratification using routinely available hospital data. Full article

Klebsiella pneumoniae is a member of the six highly virulent and antibiotic-resistant bacterial pathogens group (ESKAPE) and poses a significant threat to public health due to its ability to cause both hospital and community-acquired infections. Recent health concerns have emerged about heat-tolerant bacterial contamination in hospital settings, particularly those associated with infant formula preparation. This study aims to evaluate the heat survival of 10 clinical K. pneumoniae strains in infant formula and to investigate the correlation between heat tolerance and the presence of heat shock resistance genes, particularly the clp family of ATPases. Ten strains of K. pneumoniae were exposed to heat at 55 °C for 30 min in infant formula. We assessed their survival rates and determined their D-values. Additionally, we screened for the presence of clpC family genes across representative strains. A wide variation in heat tolerance was observed among the strains. Strain 1701 (ST247, capsular antigen profile O3:K1) exhibited the highest heat tolerance, with a D-value of 12.9 min at 55 °C. The other strains exhibited moderate-to-low heat tolerance. Notably, strain 1701 was the only one that contained the clpC2 gene, suggesting a potential association between the clp gene family and heat resistance. Our results indicate that specific heat shock resistance genes, such as clpC2, may be associated with enhanced heat tolerance observed in K. pneumoniae strains. These findings highlight the potential role of heat shock proteins in bacterial persistence within neonatal healthcare environments. Full article

Background/Objectives: Frank’s sign (FS), an acquired diagonal earlobe crease, has been associated with underlying cardiovascular (CV) disease. Pneumonia, a leading cause of hospitalization, may trigger CV events. FS may help identify patients at increased risk of CV complications following pneumonia. We aimed to evaluate the association between FS and CV events following pneumonia. Methods: We conducted a single-center prospective cohort study of internal medicine patients hospitalized with community-acquired pneumonia at a secondary hospital in Switzerland, followed for 18 months. FS was assessed at inclusion by trained investigators. Baseline characteristics were recorded. The primary outcome was a composite of CV endpoints: new-onset atrial fibrillation/flutter, myocardial infarction, hospitalization for heart failure, peripheral arterial ischemic events, or stroke. Events were identified through hospital records and general practitioner data between 2020 and 2023. Results: Among 203 patients (median age 76.0 years [IQR 65.0 to 83.0]; 41.4% female), 71.2% had FS. During follow-up, 103 CV events occurred. In univariate Cox analysis, FS was associated with an increased hazard of CV events (p = 0.042). After adjustment for confounders, FS was not significantly associated with CV events (HR 0.97; 95% CI 0.59–1.59). Only a history of CV disease and CV risk factors were associated with an increased hazard of subsequent cardiovascular events following pneumonia. Conclusions: In this population of patients hospitalized with pneumonia, Frank’s sign was not independently associated with cardiovascular events and appears to reflect underlying cardiovascular risk burden. It should not be interpreted as an independent prognostic marker. Full article

Background: Mycoplasma pneumoniae (MP) is an important pathogen responsible for community-acquired respiratory infections in children. Global surveillance during the COVID-19 pandemic revealed a marked decline in MP activity. However, beginning in early summer 2023, multiple regions across China reported an unexpected resurgence of MP infections, highlighting the need for detailed epidemiological analysis. Objective: This study aimed to characterize the epidemiological features of MP seropositivity among children in Chengdu, southwest China, and to compare its patterns between the COVID-19 pandemic and post pandemic periods. Methods: A retrospective analysis was conducted on MP testing data from 39,552 children with acute respiratory infections who were treated at West China Second University Hospital, Sichuan University, between January 2022 and December 2023. Results: Both the number of MP tests conducted and the seropositivity rate were significantly lower during the pandemic period than during the post pandemic phase. Compared with male children, female children were more susceptible to MP seropositivity. In terms of age distribution, seropositivity rates were highest among toddlers (1–3 years) and school-aged children (6–14 years). During the pandemic period (2022), MP antibody-positive cases were observed mainly between January and July, whereas in the post pandemic phase (2023), the epidemic peak shifted from June to December. Conclusions: In this single-centre study in Chengdu, nonpharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic was associated with a marked reduction in MP transmission. After these restrictions were lifted, a rebound in MP antibody positivity was observed among children in Chengdu, compared to the NPI period (2022), the post-NPI period (2023) showed a later seasonal peak, which may represent a delayed return to pre-pandemic patterns. Continuous strengthening of MP surveillance is necessary to provide early warning of potential resurgences and outbreak risks. Full article

Background/Objectives: Ceftaroline fosamil (CFT) is a fifth-generation cephalosporin approved in Spain for skin and soft tissue infections and community-acquired pneumonia. CFT may also be useful against endovascular infections. This real-world study aimed to evaluate its effectiveness and safety in patients with Gram-positive (GP) infective endocarditis (IE). Methods: This observational, retrospective multicenter study enrolled adults with GP-IE treated with CFT for ≥48 h. Recruitment extended from CFT incorporation in participating hospitals through May 2024. Data were gathered on demographic, clinical, and microbiological variables, adverse effects, overall and IE-related mortality, relapses, and a composite unfavorable outcome. Results: Seventy-six patients (65.8% male) were enrolled, with a mean age of 68.9 ± 12.8 years and an age-adjusted Charlson index of 4; 55.3% had previous moderate/severe valvular heart disease, 35.5% had atrial fibrillation, 34.2% chronic heart failure, 17.1% chronic kidney disease, and 22.4% septic shock. IE was native valve-related in 53.9%, involving the aortic valve in 38.2% and the mitral in 30.3%. Staphylococcus aureus was isolated in 48.7%, being methicillin-resistant in 40.5% of cases. CFT was salvage therapy in 65.8% and combined with other antibiotics in 94.7%. Valve replacement was indicated in 64.5% but performed in only 67.3% of these. At six months, the adverse effect rate was 9.2%, overall crude mortality 38.2%, infection-related mortality 28.9%, and composite unfavorable outcome 40.1%. In multivariate analysis, mortality-related factors were age-adjusted Charlson index, septic shock, and methicillin-sensitive S. aureus. Conclusions: CFT showed favorable outcomes and acceptable safety in the real-life treatment of GP-related IE in clinically complex patients with high comorbidity and previous antibiotic therapy failures. Full article

Background/Objectives: Mycoplasma pneumoniae (MP) is a frequent cause of community-acquired pneumonia, but it is increasingly recognized for extrapulmonary complications, specifically Mycoplasma pneumoniae-induced rash and mucositis (MIRM). This systematic review aims to comprehensively assess the frequency of clinical features, diagnostic criteria and outcomes of oral mucositis in patients with confirmed MP infection. Methods: A systematic review was conducted following PRISMA guidelines across PubMed, Web of Science and Scopus, covering the period 2015–2025. Inclusion criteria encompassed in vivo studies, case reports, and case series in English focusing on MP-associated mucositis. Methodological quality was assessed using JBI checklists for case-based evidence and the Newcastle–Ottawa Scale for cohort studies. Two clinical cases were reported. Results: Out of 242 identified records, 42 studies were included, involving 140 patients with a notable male predominance (62%). Oral involvement was reported in 92.9% of cases, often characterized by severe ulcerations, hemorrhagic crusting, and debilitating pain. Intensive Care Unit admission was required in 21.5% of cases due to severe systemic or mucosal disease, with 14.3% necessitating parenteral nutrition. Quality assessment indicated moderate-to-high methodological rigor across most included studies. Conclusions: MIRM represents a significant clinical entity where oral mucositis is a dominant feature, often preceding or overshadowing respiratory symptoms. Early recognition by oral health professionals is crucial to avoid misdiagnosis, ensure appropriate multidisciplinary care, and implement supportive or immunomodulatory therapies that reduce morbidity and hospitalization length. Full article

Background and Clinical Significance: Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant disorder caused by pathogenic variants in the SERPINA1 gene, resulting in reduced circulating alpha-1 antitrypsin (AAT) or production of dysfunctional protein. AAT is the principal inhibitor of neutrophil elastase, and its deficiency leads to unchecked proteolytic activity, progressive destruction of lung parenchyma, and increased susceptibility to infections. Severe deficiency, particularly in individuals homozygous for the Z allele (PI*ZZ), predisposes to early-onset panacinar emphysema, chronic airflow obstruction, and liver disease. Despite its clinical relevance, AATD remains markedly underdiagnosed and is frequently misclassified as smoking-related chronic obstructive pulmonary disease (COPD), delaying access to disease-modifying therapy, genetic counselling, and preventive strategies. Early recognition is therefore essential to improve outcomes. Case Presentation: We report the case of a 68-year-old ex-smoker with a long-standing diagnosis of “COPD” who presented with acute-on-chronic type 2 respiratory failure and community-acquired pneumonia. Spirometry revealed severe airflow obstruction, and high-resolution computed tomography demonstrated extensive basilar panlobular emphysema, raising suspicion for AATD. Serum AAT concentration was critically low at 26.8 mg·dL⁻¹, and isoelectric focusing confirmed a PI*ZZ phenotype. Next-generation sequencing identified homozygosity for the SERPINA1 c.1096G>A (Z) variant, with no additional pathogenic alleles. Cascade family screening revealed multiple heterozygous PI*MZ relatives. Before augmentation therapy could be initiated, the patient developed severe Legionella pneumophila pneumonia with secondary bacterial superinfection, progressing to refractory septic shock and death. Conclusions: This case illustrates how AATD can masquerade as smoking-related COPD for years, leading to missed opportunities for timely intervention. It underscores the importance of testing all adults with COPD or refractory asthma at least once, regardless of age or smoking history. Early diagnosis enables initiation of augmentation therapy, targeted vaccination, lifestyle modification, and genetic counselling, ultimately improving prognosis and reducing preventable morbidity and mortality. Full article

Human adenovirus type 7 (HAdV-7) is a significant pathogen responsible for viral community-acquired pneumonia in children. To date, no specific antiviral agents have been approved for clinical use against HAdV infections. Traditional Chinese medicine (TCM) mixtures have shown promising potential in managing viral pneumonia. This study aimed to evaluate the antiviral activity of Yuanzhixingrenheji (YZ), a hospital-prepared TCM formulation from Beijing Children’s Hospital, against HAdV-7. Initial screening of four hospital formulations (Feiyanheji, Qingjieheji, Yindaizhikeheji, and Yuanzhixingrenheji) using a CCK-8 assay revealed that YZ exhibited the lowest cytotoxicity. In vitro, YZ pretreatment and post-infection treatment exhibited dose-dependent antiviral activity against HAdV-7 in A549 cells, significantly suppressing the DBP mRNA level and protein expression while reducing viral genome copies, HAdV-7-GFP fluorescence, hexon fluorescence, and DBP nuclear localization. In the hDSG2^+/+ C57BL/6 mouse model of HAdV-7 infection, YZ effectively mitigated infection-induced body weight loss and substantially reduced viral loads in lung tissue. Furthermore, a clinical retrospective analysis indicated that YZ treatment significantly decreased post-hospitalization serum C-reactive protein levels of pediatric patients with HAdV infection in various disease severities. Compared with conventional treatment, YZ treatment also significantly reduced peak temperature and shortened the duration of fever in children with HAdV infection, supporting its therapeutic potential. In summary, this study provides the first integrated evidence from in vitro, in vivo, and clinical retrospective investigations, demonstrating that the TCM mixture YZ has significant anti-HAdV-7 activity and clinical efficacy. Characterized by a favorable safety profile and low economic burden, YZ is a promising candidate for the treatment of pediatric adenovirus pneumonia. Full article