Search Results (789)

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/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major global health problem. Drug resistance and the limitations of sputum-based diagnostic methods highlight the need for additional host-response biomarkers. Protein tyrosine phosphatase receptor type O (PTPRO) has been implicated in inflammatory signaling and macrophage immune regulation, but its relationship with TB-related host transcriptional responses remains unclear. This study aimed to identify and preliminarily evaluate a PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. Methods: Genes correlated with PTPRO expression were first screened using TCGA-LUSC as a large human transcriptomic discovery resource. The resulting candidate genes were then filtered in TB-related whole-blood datasets by intersecting genes upregulated in TB compared with healthy controls, pneumonia, and lung cancer. This strategy yielded a five-gene PTPRO-related signature, termed PO5. The signature was evaluated in independent GEO cohorts and further explored by RT-qPCR in H37Ra-infected THP-1-derived macrophages and in a small clinical blood cohort. A PO5-derived TB risk score was calculated for each sample, and receiver operating characteristic analysis was used to assess discriminatory performance. Changes in TB risk scores during anti-TB treatment were also examined. Results: PTPRO expression was increased in TB whole-blood transcriptomic data and in H37Ra-infected macrophages. In public datasets, PO5 showed potential for distinguishing TB from healthy controls, latent TB, pneumonia, and lung cancer. PO5-derived TB risk scores also decreased after anti-TB treatment. In the exploratory clinical cohort, several PO5 genes showed expression changes in the same general direction as those observed in the public datasets, although the small sample size limited the strength of this evidence. Conclusions: PO5 represents a preliminary PTPRO-related blood transcriptional signature with potential relevance to TB discrimination and treatment-response assessment. These findings remain exploratory and require validation in larger prospective multicenter cohorts, together with further mechanistic studies. Full article

Background/Objectives: The clinical determinants and functional relevance of persistent lung ultrasound (LUS) abnormalities after COVID-19 pneumonia remain poorly characterized. We aimed to identify determinants of qualitative LUS abnormalities and global lung involvement assessed by the LUS score, and to evaluate their association with persistent dyspnoea. Methods: We conducted a prospective observational study that included 261 patients who were hospitalized for COVID-19 pneumonia and were assessed 1–6 months after discharge. A standardized 14-zone LUS protocol was used to assess qualitative abnormalities (pleural line irregularity, ≥3 B-lines, and subpleural consolidations) and to calculate the LUS score. Associations with clinical variables, including dyspnoea assessed by the modified Medical Research Council (mMRC) scale, were analyzed using multivariable logistic regression. Results: The severity of the acute pneumonia episode emerged as the strongest determinant of qualitative LUS abnormalities and elevated LUS score (>6). Increasing age was independently associated with ultrasound findings. Persistent dyspnoea (mMRC ≥ 1) was associated with all qualitative abnormalities and with a higher prevalence of elevated LUS score (56.6% vs. 22.1%; p < 0.001). A graded association was observed between dyspnoea severity and both qualitative findings and LUS score. An increase in dyspnoea from baseline (ΔmMRC ≥ 1) remained independently associated with an elevated LUS score. Conclusions: Persistent LUS abnormalities are strongly associated with the severity of the acute episode. The LUS score provides a robust, clinically meaningful measure of residual lung involvement and shows a stronger association with persistent dyspnoea than qualitative findings, supporting its role in follow-up and risk stratification. Full article

The biliary tract, long considered a sterile environment, is now recognized to harbor a resident microbiota with important implications for health and disease. This review aims to summarize current knowledge on the composition and function of the biliary microbiota in physiological conditions, and its alterations in pathological states such as infection and lithiasis, with a particular focus on antimicrobial resistance. In healthy individuals, the biliary microbiota appears to be shaped by bile acids and gut–bile axis interactions, playing a role in local immune modulation. In disease, microbial dysbiosis contributes to conditions such as acute cholecystitis, cholangitis, and gallstone formation, with distinct microbial signatures linked to specific stone types. Common biliary pathogens, including E. coli, Enterococcus spp., Pseudomonas spp., and K. pneumoniae, often exhibit concerning resistance patterns, impacting therapeutic strategies. Emerging evidence highlights the interplay between intestinal and biliary microbiota, suggesting potential diagnostic and prognostic applications. Understanding these dynamics opens new avenues for microbiota-informed antibiotic stewardship, targeted microbiota modulation, and precision medicine approaches. Further research, particularly culture-independent and longitudinal studies, is crucial to fully elucidate the clinical significance of the biliary microbiota and to integrate microbiota profiling into patient management strategies. Full article

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research. Full article

Background/Objectives: Escherichia coli bacteremia is a major cause of morbidity, mortality, and healthcare expenditure. The increasing prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) complicates management and resource utilization. This study aimed to identify clinical predictors of higher hospital costs in E. coli bacteremia. Methods: We conducted a cross-sectional study of hospitalized patients with E. coli bacteremia in Surabaya, Indonesia (2022–2024). Hospital costs were categorized into bed costs, diagnostic costs, pharmacy costs, antibiotic costs, total costs, and daily costs. Costs were compared between ESBL and non-ESBL cases. Predictors of higher hospital costs were analyzed using generalized linear models with a Gamma distribution and log-link. Results: Among 209 patients, 131 (62.7%) had ESBL-producing E. coli. ESBL E. coli bacteremia was associated with significantly higher bed, diagnostic, pharmacy, total, and daily hospital costs than non-ESBL cases, while antibiotic costs were similar. ESBL E. coli bacteremia was associated with higher diagnostic and daily costs. High-care/ICU stay was the strongest predictor of increased costs. Pneumonia and infection source influenced cost components. Longer hospitalization increased total cost but reduced daily cost. Conclusions: Hospital costs in Escherichia coli bacteremia are driven by antimicrobial resistance, disease severity, and healthcare utilization. Targeted strategies such as antimicrobial stewardship and optimized critical care use are essential to reduce the economic burden. Full article

Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment. Full article

Background/Objectives: Staphylococcus aureus, particularly methicillin-resistant strains, is a leading cause of severe pneumonia. Understanding local molecular epidemiology, including virulence gene profiles and antimicrobial resistance (AMR) mechanisms, is crucial for effective infection control. This pilot study aimed to characterize S. aureus isolates from pneumonia patients in Karaganda, Kazakhstan. Methods: We collected 48 respiratory samples from patients with pneumonia across three medical institutions. Bacterial identification was performed using MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was carried out using European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Whole-genome sequencing of S. aureus isolates was conducted on an Ion Torrent S5 platform. Genomic analysis included multilocus sequence typing (MLST), identification of virulence and AMR genes, and phylogenetic reconstruction. Results: S. aureus was identified in 14.6% (n = 7) of pneumonia cases included in this study. All isolates (100%, n = 7) were phenotypically resistant to benzylpenicillin. The mecA gene was detected in 57.1% of isolates (n = 4), while phenotypic resistance to methicillin was observed in 28.6% (n = 2) of the isolates. Resistance to azithromycin (57.1%, n = 4) and levofloxacin (42.9%, n = 3) was observed among the isolates. Two isolates (28.6%) were multidrug-resistant (MDR). Genomic analysis revealed the prevalence of the ST22 clone (57.1%, n = 4) in the studied cohort. Other sequence types were ST97, ST8, and ST45 (14.3% each). Phylogenetic analysis showed clustering consistent with MLST profiles. All isolates carried a conserved core virulence arsenal, including hemolysin (hla, hlg), biofilm-forming genes (icaADBC), immune evasion genes (sak, scn), and iron acquisition genes (isd). The Panton–Valentine leukocidin (PVL) genes were detected in three isolates. AMR gene analysis revealed the ubiquitous presence of mepA and tetracycline efflux pump genes, along with regulatory genes (arlRS, mepR, mgrA). The blaZ and ermA genes were not detected despite high phenotypic resistance to penicillin and macrolides. Conclusions: This study reports the identification of the virulent and resistant ST22 S. aureus clone in pneumonia cases in Karaganda, Kazakhstan. The discordance between phenotypic and genotypic AMR profiles underscores the necessity for integrated diagnostic approaches. Full article

The secretome of ESKAPE pathogens, including Klebsiella pneumoniae, comprises a diverse array of bioactive molecules that govern virulence, antibiotic resistance, and the establishment of an immunosuppressive microenvironment. However, the high chemical complexity of the secretome impedes the identification of key metabolites mediating pathogenesis. In this study, we profiled the metabolite composition of cell-free K. pneumoniae supernatant using a combined approach of chromatographic fractionation and Raman spectroscopy. Chromatographic separation enabled the resolution of the complex secretome and revealed fractions with distinct biochemical signatures. A key finding was the identification of Fraction 3, characterized by a unique metabolic profile: it was enriched in nucleic acid fragments, peptides containing tyrosine and methionine, polysaccharides, and stress-response metabolites (e.g., citrate), while notably lacking markers of tryptophan and sterol-like lipids. These spectral signatures suggest a potential role for Fraction 3 metabolites in intercellular communication, biofilm formation, and protection against oxidative stress. The remaining fractions also exhibited distinct biochemical profiles, defined by unique profiles of lipids, nucleotides, and amino acids. Collectively, these data underscore the critical role of specific K. pneumoniae secreted metabolites to pathogen survival and host immune modulation. The combined approach effectively resolves functionally relevant secretome fractions, offering new avenues for identifying diagnostic and therapeutic targets for multidrug-resistant infections. Full article

Idiopathic pulmonary fibrosis (IPF) and autoimmune usual interstitial pneumonia (aUIP) share overlapping clinico-radiological features, complicating differential diagnosis. Electronic nose (eNose) technology characterizes exhaled breath profiles (“breathprints”) and may offer a non-invasive diagnostic approach in fibrotic interstitial lung diseases. To evaluate whether eNose breathprint analysis can discriminate between IPF and aUIP. In this cross-sectional study of 60 patients (34 IPF, 26 aUIP), breathprints were analyzed using principal component analysis (PCA, retaining eigenvalues > 1). Group differences were assessed via independent t-tests. Linear discriminant analysis (LDA) with leave-one-out cross-validation evaluated the discriminatory performance of PC combinations. PCA identified four principal components, with PC1 explaining 96% of the total variance. PC1 scores were significantly higher in aUIP compared to IPF (mean difference −0.53; 95% CI −1.04 to −0.02; p = 0.04); PC2-PC4 showed no significant differences (p > 0.3). LDA utilizing PC1 and PC3 achieved a cross-validated classification accuracy of 73.3% (95% CI 60.7–84.4, p < 0.05). eNose-derived breathprints showed preliminary discriminatory potential between IPF and autoimmune UIP, supporting further validation of this non-invasive adjunctive approach. Breathomics represents a promising non-invasive adjunctive tool for phenotyping fibrotic interstitial lung diseases, though larger validation studies integrating clinical and biological data are warranted. Full article

Background/Objectives: Bloodstream infections are among the most severe infectious diseases, with mortality rates up to 25%. Delays as short as one hour in the diagnosis or initiation of the appropriate antimicrobial therapy can significantly worsen patient outcomes. Methods: This retrospective study, in an Italian 900-bed hospital from January 2019 to December 2024, evaluates the impact of a 24/7 reorganization of the clinical microbiology laboratory, adding a night shift to ensure around-the-clock processing and introducing a fast-track diagnostic pathway to prioritize the blood cultures from critically ill patients (called urgent blood cultures) in terms of turnaround times for Gram staining, microorganism identification, and resistance marker detection. Results: A total of 194,171 blood cultures were processed. Following the implementation of the 24/7 model, the median Gram stain turnaround time decreased from 4.46 to 1.40 h, microorganism identification turnaround time decreased from 5.75 to 2.35 h, and resistance marker turnaround time from 6.97 to 2.68 h. Significant reductions were observed especially during night shifts. Urgent blood cultures yielded a higher positivity rate (16.22% vs. 13.04%) and included the isolation of time-critical bacteria that can cause meningitis, such as Streptococcus pneumoniae. Conclusions: The continuous around-the-clock processing of blood culture and prioritized blood cultures for critically ill patients significantly reduced reporting times, particularly overnight. This model enhances early sepsis management and exemplifies how tailored and precision microbiology, supported by strong interdisciplinary collaboration and effective communication, can enhance earlier targeted antimicrobial treatment. Full article

Legionnaires’ disease is a rare cause of atypical pneumonia associated with a high mortality rate among untreated patients. In Romania, the disease has historically been underreported due to insufficient surveillance and limited diagnostic capacity. The aim of this study was to describe the characteristics of Legionnaires’ disease cases admitted to a specialized infectious disease hospital between 2023 and 2024, with a particular focus on a cluster associated with travel to a spa resort. Most cases included in our study (31/36) were confirmed by urinary antigen testing, while one case was confirmed by a significant increase in the level of specific antibodies against Legionella pneumophila serogroup 1 in paired serum samples. The most frequently reported symptom was fever (28/32), followed by chills (24/32). Among the 32 confirmed cases, 3 patients died. Two cases were identified as part of a family cluster involving a father and son who had undergone physiotherapy at a balneary resort. Both patients presented with fever and gastrointestinal symptoms, and radiological investigations confirmed mixed pneumonia associated with an intense inflammatory syndrome. In the father’s case, hepatic involvement and interstitial nephritis were also identified. Early diagnosis based on epidemiological data, clinical predictive scores, and laboratory investigations would allow timely administration of targeted antibiotic therapy and may contribute to reduced mortality. Full article

Background: Molecular diagnostics may detect several respiratory pathogens simultaneously with rapid turnaround times. The aim of this study was to determine the frequency and distribution of respiratory pathogens among symptomatic outpatients. Methods: All outpatients presented for testing due to suspected acute respiratory infection between 1 January and 31 December 2024 to the Teaching Institute for Public Health of Split-Dalmatia County, Croatia, and multiplex real-time PCRs for 13 respiratory pathogens were included. Results: Out of 15,437 analyzed panels, 8878 (57.5%) were positive. Single-pathogen infections dominated (82.6%), while co-infections were recorded in 17.4% of panels; therefore, a total of 10,546 individual pathogens were detected, which were mostly viruses (87.0%). The following distribution of pathogens was observed: rhinovirus/enterovirus in 38.9% of positive results, influenza A virus in 14.5%, SARS-CoV-2 in 9.5%, parainfluenza virus in 7.9%, respiratory syncytial virus in 7.3%, Mycoplasma pneumoniae in 4.9%, Bordetella pertussis in 4.6%, human metapneumovirus in 4.2%, adenovirus in 3.4%, Chlamydia pneumoniae in 3.4%, influenza B virus in 1.3%, Bordetella parapertussis in 0.1% and Legionella pneumophila had one positive result. The first trimester of the year had the highest number of positive test panels (47.0%). Conclusions: Our study demonstrates a predominance of viral pathogens across all age groups and seasons, further supporting guideline-based practice and highlighting the importance of confirming bacterial infection before initiating antibiotic therapy. This insight into the post-pandemic circulation of respiratory pathogens may help inform public health strategies, including improved surveillance, anticipation of seasonal outbreaks, and targeted interventions, thereby supporting future pandemic preparedness and mitigation efforts. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a critical global public health challenge driven by inappropriate and excessive antimicrobial use (AMU) across human, animal, and environmental sectors. Method: This narrative review synthesizes recent evidence on antimicrobial utilization and resistance patterns. A structured search of PubMed, Scopus, and Web of Science was conducted for studies published between 2015 and 2025. Eligible sources included surveillance reports, registry-based analyses, and clinical studies. Data were qualitatively analyzed to identify key trends and regional variations. Result: Marked geographical variation in AMR was observed. Carbapenem resistance in Escherichia coli remains low globally (2–3%) but is higher in Southeast Asia (17–18%) and India (~40%). Klebsiella pneumoniae shows consistently high resistance (>40% globally; ~54% in India), while Pseudomonas aeruginosa exhibits stable resistance levels (35–45%). Resistance prevalence increases from primary to tertiary care settings, reflecting greater antimicrobial exposure. Vulnerable populations—including pediatric, elderly, pregnant, and immunocompromised patients—face higher risks of antimicrobial exposure and adverse outcomes, including nephrotoxicity, hepatotoxicity, and microbiome disruption. WHO AWaRe data indicate a global shift toward increased use of Watch-category antibiotics. Stewardship interventions, such as audit and feedback, prescribing restrictions, rapid diagnostics, and decision support systems, effectively reduce inappropriate AMU. Conclusions: Integrated, data-driven antimicrobial stewardship and robust surveillance systems are essential to mitigate the global burden of AMR. Full article

Background: Late-onset anaerobic prosthetic joint infection (PJI) is uncommon but may indicate underlying, previously asymptomatic colorectal malignancy. While the association between Streptococcus bovis group (SBG) bacteremia and colorectal cancer is well established, links between anaerobic PJIs and colorectal neoplasia are rarely reported. Anaerobic organisms originating from the gastrointestinal tract may translocate via the hematogenous route, and their presence in PJI should prompt clinicians to consider occult colorectal pathology. Methods: All periprosthetic arthroplasty infection cases between 2015 and 2025 were reviewed. Clinical records, diagnostic findings, microbiological data, and treatment outcomes were analyzed. Results: Three female patients (mean age 76.3 years) presented with late-onset PJI occurring at least five years after primary total knee arthroplasty. Causative organisms included Bacteroides fragilis, Morganella morganii, and Klebsiella pneumoniae. All patients underwent two single-stage revision surgeries and one debridement, antibiotics and implant retention (DAIR) procedure. Cross-sectional computed tomography imaging of the abdomen and pelvis (CT-AP) performed to evaluate hematogenous sources of infection consistently revealed previously undiagnosed colorectal malignancy. One patient had additional metastatic disease. Postoperative complications included one case of pulmonary embolism; no other major complications were observed. Conclusions: Anaerobic PJIs are rare, and their association with colorectal malignancy is not well established. These cases highlight the importance of evaluating potential gastrointestinal sources, including occult colorectal cancer, in patients presenting with late-onset anaerobic PJI. Full article