Multidrug-resistant (MDR) Gram-negative pathogens continue to threaten patient outcomes in intensive care units (ICUs) worldwide, particularly in regions where genomic surveillance is limited. Understanding intra-host ge...Multidrug-resistant (MDR) Gram-negative pathogens continue to threaten patient outcomes in intensive care units (ICUs) worldwide, particularly in regions where genomic surveillance is limited. Understanding intra-host genomic diversity and mobility of resistance determinants remain essential for mitigating global antimicrobial resistance (AMR) threats. Whole genome sequencing and molecular analysis were performed on three selected isolates to identify resistance and virulence determinants. The isolates exhibited complex and heterogenous resistomes shaped by extensive antimicrobial exposure during prolonged ICU care. Two genetically distinct Klebsiella pneumoniae strains (ST11 and ST15) demonstrating intra-patient strain diversity, an emerging trend in high-risk clinical settings globally, along with an Acinetobacter baumannii strain (ST944) were recovered from the same patient. Key resistance genes linked to mobile genetic elements (MGEs) were identified, including blaCTX-M-15 and blaNDM-5 in K. pneumoniae ST11 and blaADC-152 in A. baumannii. A plasmid-associated contig harbouring blaDHA-1 and qnr resistance genes represented a 'high-risk' mobile platform with international similarity in K. pneumoniae, highlighting the global circulation of resistance plasmids. Virulence profiling revealed conserved and unique determinants, including biofilm, siderophore, and secretion loci, with one isolate carrying a complete Yersiniabactin locus associated with MGEs. This study provides the first genome-resolved case from the Caribbean demonstrating intra-host co-existence of globally important MDR lineages and plasmid-mediated dissemination of key resistance genes. Within the global AMR challenge, this analysis offers novel insight into the convergence of resistance and virulence traits and highlights the value of localized genomic surveillance in understanding pathogen adaptation, mobility, and persistence under high antimicrobial pressure. These findings emphasize the importance of incorporating genomic data from diverse geographic regions into global AMR networks to better manage MDR ESKAPE pathogens in ICU environments.
People living with HIV frequently experience oral microbial dysbiosis, contributing to oral disease burden and reduced quality of life. Although antiretroviral therapy (ART) effectively suppresses viral replication and p...People living with HIV frequently experience oral microbial dysbiosis, contributing to oral disease burden and reduced quality of life. Although antiretroviral therapy (ART) effectively suppresses viral replication and promotes immune recovery, its longitudinal effects on the oral microbiota remain incompletely understood. This systematic review aimed to evaluate longitudinal changes in oral microbiota composition and diversity in people living with HIV before and after ART initiation. A systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251164326). Electronic searches were performed in PubMed, ScienceDirect, Wiley Online Library, DOAJ, and Google Scholar for studies published between 2015 and 2024. Eligible studies included longitudinal human studies reporting pre- and post-ART oral microbiota data using 16S rRNA gene sequencing or metagenomic approaches. Methodological quality was assessed using Joanna Briggs Institute critical appraisal tools. Due to substantial heterogeneity, findings were synthesized narratively. Six longitudinal studies met the inclusion criteria. ART was associated with partial and non-uniform modulation of the oral microbiota. Changes in beta diversity and selective taxonomic shifts were commonly reported, whereas changes in alpha diversity were inconsistent. Taxonomic alterations were more evident at the genus level, while several dominant oral genera remained stable before and after ART. Evidence linking oral microbiota changes with immune recovery was limited. Longitudinal evidence indicates that ART induces selective and heterogeneous changes in the oral microbiota without consistent normalization toward a non-HIV microbial profile, underscoring the importance of integrating oral health into long-term HIV care.
Fusobacterium nucleatum is a Gram-negative obligate anaerobic bacterium typically found as a commensal in the human oral cavity, gastrointestinal and female genital tract. While it is a common cause of endodontic infecti...Fusobacterium nucleatum is a Gram-negative obligate anaerobic bacterium typically found as a commensal in the human oral cavity, gastrointestinal and female genital tract. While it is a common cause of endodontic infections, it is a rare cause of infective endocarditis (IE), which can lead to high morbidity if diagnosis is delayed due to the challenges of culturing anaerobic bacteria. The case of a 75-year-old male patient with a history of type 2 diabetes who presented with high fever, rigors, and hemodynamic instability is presented herein. Physical examination revealed a new systolic murmur. Initial investigations identified inflammatory syndrome and elevated liver enzymes. Further imaging via contrast-enhanced ultrasound and computed tomography confirmed two abscesses in the left lobe of the liver. Blood cultures grew F. nucleatum, and a transesophageal echocardiogram demonstrated vegetation on the aortic valve. The patient met the Modified Duke criteria for a diagnosis of infective endocarditis. It was later elicited that the patient had undergone dental interventions one month prior to admission. The patient was successfully treated with a six-week course of targeted antimicrobial therapy consisting of ceftriaxone and metronidazole, resulting in favorable clinical recovery. Fusobacterium species are rare but significant causes of invasive infections such as liver abscesses and IE. This case emphasizes that anaerobic pathogens should be suspected in patients presenting with unexplained sepsis, concomitant deep-seated abscesses, or a history of recent dental procedures. Early use of echocardiography and anaerobic blood cultures are essential for the timely diagnosis of these rare clinical entities.
The emergence of highly virulent and multidrug-resistant Salmonella strains continues to pose a major global public health concern. Building on our previous investigation of 80 Salmonella isolates obtained from avian and...The emergence of highly virulent and multidrug-resistant Salmonella strains continues to pose a major global public health concern. Building on our previous investigation of 80 Salmonella isolates obtained from avian and human sources in northeastern Algeria (Annaba and Constantine) over a three-year period (2017-2019), in which their resistance profiles to 15 antimicrobial agents were assessed, the present study further explores the molecular features of virulence by targeting two additional plasmid-encoded genes, spvB and spvR. All isolates were subjected to polymerase chain reaction (PCR) amplification using gene-specific primers. The results revealed that spvB was detected in 86.25% of isolates, while spvR was identified in 73.75%, suggesting a strong association with strains capable of causing severe systemic infections. When compared with previous reports, notable geographical variations were observed, which may reflect differences in host reservoirs, ecological conditions, and selective pressures arising from antimicrobial use. The coexistence of spv virulence genes and multidrug-resistant (MDR) phenotypes in our isolates underscores the substantial risk of dissemination of highly pathogenic and resistant Salmonella strains between animals and humans. These findings highlight the need to integrate virulence gene surveillance into existing antimicrobial resistance monitoring programs to better understand and manage the zoonotic transmission dynamics of Salmonella in Algeria.
The complex interplay between chronic metabolic disorders and acute cardiovascular decompensation represents a critical frontier in cardiology. This integrative research program conducted at Chongqing Medical University...The complex interplay between chronic metabolic disorders and acute cardiovascular decompensation represents a critical frontier in cardiology. This integrative research program conducted at Chongqing Medical University systematically examines the gut-liver-heart axis across the cardiovascular disease spectrum through three interconnected studies. First, a case-control investigation of coronary artery disease (CAD) patients with and without nonalcoholic fatty liver disease (NAFLD) revealed distinct intestinal dysbiosis patterns characterized by increased Coprococcus and Veillonella alongside decreased Parabacteroides, Bacteroides fragilis, and Bifidobacterium longum, with these microbial alterations correlating significantly with body mass index, triglyceride levels, and hepatic transaminases. Second, a retrospective cohort study of acute myocardial infarction complicated by cardiogenic shock demonstrated that elevated admission bilirubin (HR = 1.020, P = 0.003) and alanine aminotransferase independently predicted 30-day mortality, while serum albumin exerted protective effects (HR = 0.955, P < 0.001). Third, analysis of a comprehensive clinical registry illuminated the systemic clustering of metabolic, renal, and inflammatory abnormalities that underpin both chronic cardiometabolic disease and acute cardiovascular collapse. Collectively, these findings establish a pathogenic continuum wherein chronic intestinal dysbiosis and subclinical hepatic dysfunction create a vulnerable substrate that amplifies injury during acute ischemic events. This research framework provides mechanistic insights into the gut-liver-heart axis and proposes integrated biomarker panels for risk stratification across cardiovascular disease stages.
Patients with advanced non-small cell lung cancer (NSCLC) are prone to lower respiratory tract infection (LRTI) during immune checkpoint inhibitor (ICI) treatment, but the pathogen spectrum and clinical impact remain unc...Patients with advanced non-small cell lung cancer (NSCLC) are prone to lower respiratory tract infection (LRTI) during immune checkpoint inhibitor (ICI) treatment, but the pathogen spectrum and clinical impact remain unclear. This study provides comprehensive microbiological characterization of pathogen spectrum, molecular resistance mechanisms, and prognostic significance of LRTI during ICI treatment in patients with advanced NSCLC. A single-center retrospective cohort design was adopted, and 903 patients with advanced NSCLC who first received PD-1 or PD-L1 inhibitor treatment between January 1, 2019 and November 30, 2023 were included. Molecular characterization of resistant isolates was performed using PCR and sequencing for ESBL genes (blaCTX-M, blaSHV, blaTEM), carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48, blaOXA-23), and mecA, with multilocus sequence typing (MLST) for clonality analysis. Competing risk models estimated cumulative incidence of first LRTI; time-dependent Cox models evaluated associations with overall survival (OS) and progression-free survival (PFS). Among 903 patients, 176 (19.49%) developed LRTI during ICI treatment. Among 243 infection episodes, any phenotypic resistance was identified in 31 episodes (12.76%). Of 24 available resistant isolates, molecular characterization revealed blaCTX-M-15 as the predominant ESBL determinant (87.5%), blaKPC-2 and blaNDM-1 in CRE, blaVIM-2 and blaIMP-4 in CRPA, and blaOXA-23 in CRAB. MLST identified high-risk clones: K. pneumoniae ST11 (n = 3) and ST15 (n = 2), E. coli ST131 (n = 2), Pseudomonas aeruginosa ST235 (n = 3), A. baumannii ST2 (n = 6), and MRSA ST239 (n = 2). Older age, male sex, higher ECOG score, stage IV disease, COPD, ILD, baseline corticosteroid exposure, and higher NLR were associated with increased infection risk (all P < 0.05). First LRTI was independently associated with worse OS (HR = 1.78) and PFS (HR = 1.41). Fungal infection (HR = 2.48), mixed infection (HR = 2.34), resistance-associated infection (HR = 2.61), and severe infection (HR = 2.96) indicated worst prognosis. LRTI during ICI treatment in advanced NSCLC carries substantial burden and is associated with poor prognosis. Molecular characterization reveals that resistant infections are driven by established epidemic clones (ST2 CRAB, ST11 CRKP, ST235 CRPA, ST131 ESBL-EC), highlighting the need for enhanced infection control and targeted antimicrobial strategies in this vulnerable population.
Acute lung injury (ALI) is a significant post-operative complication of liver transplant (LT), with mounting evidence suggesting a role for the gut-lung axis. However, the mechanistic link between gut microbiota dysbiosi...Acute lung injury (ALI) is a significant post-operative complication of liver transplant (LT), with mounting evidence suggesting a role for the gut-lung axis. However, the mechanistic link between gut microbiota dysbiosis and ALI pathogenesis in LT recipients remains poorly understood. This hybrid translational investigation integrates transcriptomic profiling (bulk and single-cell RNA-seq), immune infiltration analysis, fecal microbiota composition (16S rRNA), and predictive functional profiling in ALI vs. non-ALI (NALI) LT patients. Machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to identify key gene biomarkers. Microbiota-host gene correlations and canonical correspondence analysis (CCA) were performed to evaluate multi-omic relationships. ALI patients exhibited reduced gut microbial diversity and increased abundance of Enterococcus and Escherichia-Shigella, alongside a depletion of beneficial taxa (Faecalibacterium, Bacteroides). CXCL3, CD48, and IRAK3 were identified as robust ALI biomarkers (Area Under the Curve >0.83), validated in both serum and Bronchoalveolar Lavage Fluid. These genes correlated positively with pro-inflammatory microbes and immune cell infiltration. Functional prediction revealed enrichment in lipopolysaccharide biosynthesis, Toll-like receptor signaling, and bacterial chemotaxis. CCA confirmed that microbiota variation significantly explained host transcriptomic variance. Our study uncovers a functional gut-lung immunological axis in post-LT ALI. Gut dysbiosis modulates immune gene expression and lung inflammation, suggesting that the microbiome serves as a potential source of diagnostic biomarkers and therapeutic targets in transplant-associated lung injury.
Acinetobacter baumannii is a major cause of hospital-acquired infections and has emerged as a critical multidrug-resistant (MDR) pathogen with limited therapeutic options. In this study, two MDR clinical isolates from a...Acinetobacter baumannii is a major cause of hospital-acquired infections and has emerged as a critical multidrug-resistant (MDR) pathogen with limited therapeutic options. In this study, two MDR clinical isolates from a tertiary care hospital in Chennai, India, selected based on their strong biofilm-producing capacity, were subjected to whole-genome sequencing (WGS) to characterize their resistome, virulome, and genomic features. Both isolates exhibited resistance to β-lactams, carbapenems, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, while remaining susceptible to tigecycline and colistin. Genomic analysis identified key carbapenemase genes blaOXA-23, blaOXA-51, and blaOXA-144 along with additional resistance determinants including blaADC-76 and blaPER-7, aminoglycoside-modifying enzymes (ant(3″)-Ia and aph(6)), tetracycline resistance genes (tet(A), tet(B), and tet(R)), macrolide resistance gene msr(E), sulfonamide resistance gene sul1, and chloramphenicol efflux gene cmlA5. Fluoroquinolone resistance was associated with mutations in the quinolone resistance determining regions, including an S81L substitution in gyrA and multiple substitutions in parC. Virulence profiling revealed biofilm-associated genes, including bap and the pgaABC operon, along with genes linked to motility and metabolic fitness. Phylogenomic analysis showed close relatedness between the isolates and reference strains, and multilocus sequence typing (MLST) assigned both isolates to sequence type ST1051, indicating a shared clonal background. The genomes also harbored diverse mobile genetic elements, prophage regions, and siderophore-associated biosynthetic gene clusters, reflecting high genomic plasticity. Overall, this study highlights the coexistence of multiple resistance and virulence determinants in biofilm-forming MDR A. baumannii, emphasizing the importance of genome-based surveillance for monitoring high-risk strains in clinical settings.
Aging is the natural process of changes that are accumulated over time and are responsible for the ever-increasing susceptibility to diseases and death. Extensive research has been done to understand the role of gut micr...Aging is the natural process of changes that are accumulated over time and are responsible for the ever-increasing susceptibility to diseases and death. Extensive research has been done to understand the role of gut microbiota in aging, however, limited progress has been made. Thus, considering the need of the hour we have tried to give a new perspective to this body of research by delving deep into all major factors that are associated with gut microbiome and aging. This review presents a holistic view of the relation between gut microbiome and aging starting from hallmarks of aging and evolution of gut microbiome over lifespan to intricate mechanisms like inflammaging, immunosenescence, gut-brain axis, mitochondrial dysfunction, nutrient imbalance and cardiac implications. In addition, it highlights different therapies like fecal microbiota transplantation, omics and metabolomics studies, and gut modulation therapies that show a promising future towards regulation of gut microbiota for aging interventions. More importantly, this review is an addition to the existing literature which advocates gut microbiome as an additional hallmark of aging, summarising the known status of the research in this field, contributing to developing gut microbiota targeted healthy aging.
Immune checkpoint inhibitors improve outcomes in solid tumors, but immune-related pneumonitis (irP) can lead to treatment interruption and even death; current stratification mainly relies on medical history and imaging,...Immune checkpoint inhibitors improve outcomes in solid tumors, but immune-related pneumonitis (irP) can lead to treatment interruption and even death; current stratification mainly relies on medical history and imaging, lacking reproducible organ-specific biomarkers. This prospective cohort study evaluated the association of baseline lower respiratory tract microbiota features and bacterial load with the risk of PD-1/PD-L1-related irP. Bronchoalveolar lavage was performed before immunotherapy; 16S sequencing derived the Pathogen-Enrichment Score (PES), and quantitative PCR quantified total bacterial load. The primary endpoint was first occurrence of grade ≥2 irP within 6 months. Firth-corrected multivariable logistic regression adjusted for prior thoracic radiotherapy, baseline interstitial lung disease, and recent antibiotic use. Of 294 evaluable cases, 34 developed grades ≥2 irP. Baseline total bacterial load was significantly higher in patients who later developed irP, showing a monotonic dose-response relationship with risk (nonlinearity P = 0.183); adjusted odds ratio = 1.58 per 1 log10 copies/mL (P = 0.024). PES was also elevated (adjusted odds ratio = 1.43 per 1 SD, P = 0.033). The dysbiotic phenotype was characterized by reduced diversity and enrichment of Streptococcus, Veillonella, and Haemophilus, genera commonly associated with oral microbiota and aspiration. Adding PES and bacterial load to a clinical model improved discrimination (AUC 0.81 vs 0.73, P = 0.019) and reclassification (categorical NRI = 0.24, P = 0.004). Event rates across risk strata were 2.24, 13.46, and 32.65%. Baseline lower respiratory tract dysbiosis and elevated bacterial load indicate higher irP risk; adding these microbiologic measures to a clinical model improves prediction and risk stratification.
Carbapenem-resistant Enterobacterales (CRE) infections are difficult to treat and are associated with high morbidity and mortality. Therefore, it is important to rapidly identify the carriers. This study aimed to investi...Carbapenem-resistant Enterobacterales (CRE) infections are difficult to treat and are associated with high morbidity and mortality. Therefore, it is important to rapidly identify the carriers. This study aimed to investigate the clinical and microbiological risk factors associated with CRE colonization, infection, and mortality rates in adult intensive care unit (ICU) patients. A retrospective cohort analysis was performed in the adult ICU of Selahaddin Eyyubi State Hospital, Diyarbakır, Türkiye, between October 2022 and February 2024. Rectal swabs were obtained at ICU admission and weekly thereafter. Based on clinical, laboratory, and microbiological findings, the patients were categorized into colonized or infected groups. Demographic parameters, comorbidities, device use, previous antibiotic exposure, and mortality were analyzed using logistic regression, Kaplan-Meier survival estimates, and Cox proportional hazard modeling. Of the 420 patients, 69 (16.4%) were CRE-positive, 46 (66.7%) remained colonized, and 23 (33.3%) developed infections. The most frequent isolates were Klebsiella pneumoniae (63.8%) and Escherichia coli (36.2%). Independent risk factors for colonization included male sex, prolonged hospitalization, pulmonary or cerebrovascular disease, and prior exposure to β-lactam/β-lactamase inhibitors or cephalosporin antibiotics. CRE infection was related to prior β-lactam/β-lactamase inhibitor and carbapenem use. Mortality was 65.2% in the colonized-infected group versus 13% in those with colonization alone (P < 0.001). Overall survival was similar for CRE-positive and CRE-negative patients, but infected patients had higher mortality rates than colonized patients. CRE colonization in ICU patients poses a substantial risk once infection develops and is closely associated with broad-spectrum antibiotic exposure. These findings support routine rectal CRE screening as a key tool for identifying high-risk patients and informing antibiotic stewardship strategies aimed at preventing progression to fatal infections and improving survival.
The present study aimed to evaluate the in vitro activity of ceftazidime-avibactam (CZA), imipenem-cilastatin-relebactam (IMR), meropenem-vaborbactam (MEV), cefiderocol (CFDC), and plazomicin (PLZ), against nosocomial ca...The present study aimed to evaluate the in vitro activity of ceftazidime-avibactam (CZA), imipenem-cilastatin-relebactam (IMR), meropenem-vaborbactam (MEV), cefiderocol (CFDC), and plazomicin (PLZ), against nosocomial carbapenem-resistant Pseudomonas aeruginosa (CRPA) (n = 40), carbapenem-resistant Acinetobacter baumannii (CRAB) (n = 56), and Stenotrophomonas maltophilia (n = 50) isolates from Bulgaria (2014-2023). Antimicrobial susceptibility testing, polymerase chain reaction screening for antimicrobial resistance (AMR) determinants, and whole-genome sequencing were performed. In CRPA, blaNDM-1 (20%), blaVIM-2 (5%), and blaVIM-4 (2.5%) metallo-β-lactamase (MBL)-encoding genes were detected. Both P. aeruginosa and S. maltophilia showed absolute susceptibility to CFDC, and 78.6% of the tested A. baumannii isolates were also susceptible. All CFDC-resistant (MIC values in the range of 4-64 mg L-1) CRAB isolates (12 out of 56) were positive for blaPER-1 (n = 12) and acquired class D carbapenemase genes, as follows: blaOXA-23-like (n = 7), blaOXA-24/40-like (n = 1), and blaOXA-23-like + blaOXA-24/40-like (n = 4). Only 22.5-25% of CRPA isolates revealed susceptibility to the combined β-lactam (BL)-β-lactamase inhibitor (BLI) antimicrobials. Equal PLZ MIC50 values were reported against P. aeruginosa and A. baumannii (8 mg L-1), but higher MIC90 values against CRAB (>256 vs. 16 mg L-1). MBL-producing CRPA demonstrated absolute resistance to all BL-BLI preparations, whereas non-MBL-producing isolates possessed significantly higher susceptibility (P < 0.05), ranging from 31% (for CZA and IMR) to 34.5% (MEV). In conclusion, the emergence of MBL-positive P. aeruginosa and the associated ineffectiveness of the novel BL-BLI combinations, as well as the relatively high proportion of CFDC-resistant A. baumannii isolates, are alarming. Therefore, continuous surveillance of AMR concerning newly approved antibiotics should be the mainstay of multifaceted global and national "One Health" strategies and infection control stewardship practices in hospital settings.
Stroke-associated pneumonia (SAP) is a major complication of acute ischemic stroke. The brain-gut-lung axis suggests that post-stroke gut dysbiosis may offer independent risk information beyond clinical scores like A2DS2...Stroke-associated pneumonia (SAP) is a major complication of acute ischemic stroke. The brain-gut-lung axis suggests that post-stroke gut dysbiosis may offer independent risk information beyond clinical scores like A2DS2. The aim of this study was to evaluate the incremental predictive value of early post-stroke gut microbiome biomarkers for SAP and to construct a simplified microbiome risk score (M-score). In a prospective nested case-control study, we identified 63 SAP cases from a cohort of 551 patients with acute ischemic stroke and stool samples were collected 24-72 h post-admission. Cases were matched 1:2 (age, sex) to 126 controls. Gut microbiota was profiled via 16S rRNA sequencing. Three differentially abundant genera (prevalence ≥20%, FDR q < 0.10) were used to construct an M-score via bootstrapped regression. Independent associations were assessed with conditional logistic regression. Incremental value over the A2DS2 score was evaluated using AUC, continuous net reclassification improvement (NRI), and the Brier score. SAP cases exhibited reduced α-diversity and distinct β-diversity (both P < 0.01). Cases had higher Enterococcus and Streptococcus and lower Faecalibacterium levels (all q < 0.05). The M-score was independently associated with SAP (adjusted OR per 1-SD: 1.76, 95% CI: 1.30-2.39, P = 0.001). Adding the M-score to A2DS2 significantly improved prediction: AUC increased from 0.76 to 0.84 (ΔAUC = 0.08, P = 0.009), NRI was 0.31 (95% CI: 0.12-0.51), and the Brier score decreased from 0.18 to 0.16. Results were robust in sensitivity analyses. A gut microbiome score based on three genera provides significant independent and incremental predictive value for SAP over the A2DS2 score, enabling more precise early risk stratification after stroke.
This study investigated the synergistic effects of Helicobacter pylori (Hp) infection and small intestinal bacterial overgrowth (SIBO) on the gut microbiota structure and metabolic profiles and elucidate the underlying p...This study investigated the synergistic effects of Helicobacter pylori (Hp) infection and small intestinal bacterial overgrowth (SIBO) on the gut microbiota structure and metabolic profiles and elucidate the underlying pathophysiological mechanisms. Forty-two patients with gastrointestinal symptoms were recruited and assigned to group A (Hp+ SIBO+), B (Hp+ SIBO-), C (Hp- SIBO+), or D (Hp- SIBO-) based on their Hp infection and SIBO status. Fecal samples were collected for metagenomic sequencing and untargeted metabolomic analysis. The associations between microbiota and metabolites were evaluated using alpha/beta diversity analysis, differential species screening, metabolite identification, and Procrustes/Spearman correlation analysis. Neither Hp infection nor SIBO significantly altered the alpha or beta diversity of the gut microbiota (both P > 0.05). However, specific shifts in microbial abundance were observed. Specifically, the abundance of short-chain fatty acid-producing bacteria such as Megamonas was significantly decreased in the SIBO+ groups. Metabolomic analysis revealed significant enrichment of inflammatory metabolites (e.g., prostaglandin derivatives) in group A, disordered bile acid conjugates (e.g., chenodeoxycholylisoleucine) and nucleotide metabolism in SIBO+ groups, and abnormal lipid/carbohydrate metabolism pathways in Hp+ groups. Multi-omics integration analysis indicated a strong coupling between the microbial structure and metabolic profiles (Procrustes analysis, P < 0.05). In group A, the abundance of Faecalibacterium and Hominenteromicrobium was negatively correlated with bile acid levels, suggesting impaired bile acid transformation. Hp infection and SIBO might synergistically exacerbate gut ecological and metabolic disorders by reshaping specific microbiota and metabolic networks (enhanced inflammatory response, disrupted bile acid circulation). Their co-occurrence produces additive effects, which could explain the aggravated clinical symptoms. This study provides a theoretical basis for interventions targeting microbiota-metabolite interactions, such as probiotics and bile acid modulators.
Colorectal cancer (CRC) is a prevalent malignancy with intricate connections to gut microbiota (GM) dysbiosis, though the specific mechanisms linking microbiota-induced gene expression changes to CRC progression remain u...Colorectal cancer (CRC) is a prevalent malignancy with intricate connections to gut microbiota (GM) dysbiosis, though the specific mechanisms linking microbiota-induced gene expression changes to CRC progression remain unclear. This study employed a multi-omics approach to investigate the interplay between GM alterations and host gene expression in CRC. C57BL/6J male mice were used to establish CRC models via dextran sulfate sodium (DSS)/azoxymethane (AOM) induction. 16S rRNA sequencing was performed to characterize GM changes in CRC mouse models, revealing dysbiosis characterized by reduced Akkermansia muciniphila (Akkermansia) and elevated Desulfovibrio desulfuricans (Desulfovibrio) abundance. Transcriptomic analysis following microbiota transplantation identified significant upregulation of TANK-binding kinase 1 (TBK1) in CRC-associated microbiota recipients. In vitro experiments utilizing CRC cell models demonstrated that TBK1 overexpression activated glycolysis, as evidenced by increased extracellular acidification rate, lactate production, and elevated expression of glycolytic enzymes hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1). Functionally, TBK1 promoted cell proliferation and colony formation while inhibiting apoptosis, which were attenuated by the glycolytic inhibitor 2-deoxy-D-glucose. These findings establish TBK1 as a critical mediator linking GM dysbiosis to metabolic reprogramming in CRC, suggesting that targeting the TBK1-glycolysis axis may represent a promising therapeutic strategy for delaying CRC progression.
Nocardia species can cause serious infections, especially in immunocompromised individuals, though it can also affect immunocompetent patients. Bacteremia due to this organism is always clinically significant and is asso...Nocardia species can cause serious infections, especially in immunocompromised individuals, though it can also affect immunocompetent patients. Bacteremia due to this organism is always clinically significant and is associated with high mortality rates. We reviewed all cases of Nocardia bacteremia published in medical literature since 2019. A total of 28 studies providing data for 29 patients were included. Among all patients, 69% were male; the median age was 60 years. Overall, 23 (79.3%) patients were immunosuppressed [immunosuppressive treatment (73.9%), malignancies (34.8%), transplantation (26.1%), and autoimmune diseases (26.1%)]. Pulmonary involvement was the most frequent concomitant site of infection. Fever, cough, dyspnea, shortness of breath, and fatigue were the most commonly encountered symptoms. Seven patients (24.1%) had concurrent infections at the time of Nocardia bacteremia. Most isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). N. farcinica was the most commonly identified species (44.8%), followed by N. cyricigeorgica (25%), and N. nova (10.3%). High rates of resistance were observed for amoxicillin/clavulanic acid and ciprofloxacin (57.1% for each), clindamycin (42.9%), cefotaxime (21.4%) and imipenem (21.4%). All 14 isolates tested for trimethoprim/sulfamethoxazole (TMP/SMX) and linezolid were susceptible. The median total duration of treatment was 7.2 months. TMP/SMX was used in 78.6% of patients, carbapenems in 60.7% and linezolid in 35.7%. Mortality rate was significant (34.5%). Nocardia bacteremia is a rare but serious disseminated form of nocardiosis. Early diagnosis and prompt aggressive treatment, typically with a combination of antibiotics and long-term therapy are crucial for improving outcomes.
We describe a case of meningococcal bloodstream infection complicated by purpura fulminans in a 49-year-old woman in Tunisia in May 2025, caused by a ciprofloxacin-resistant Neisseria meningitidis. The patient presented...We describe a case of meningococcal bloodstream infection complicated by purpura fulminans in a 49-year-old woman in Tunisia in May 2025, caused by a ciprofloxacin-resistant Neisseria meningitidis. The patient presented with rapidly progressive purpura and septic shock requiring intensive care and empirical cefotaxime therapy. Blood cultures, molecular testing, and whole-genome sequencing (WGS) were investigated to characterize the N. meningitidis isolate. The strain was non-groupable and belonged to ST-175 (cc175), with BAST profile 3645 and a MenDeVAR Index indicating insufficient evidence for vaccine coverage. WGS identified penA mutations (F504L, A510V, I515V, H541N, I566V) associated with reduced amoxicillin susceptibility and a gyrA T91I mutation conferring ciprofloxacin resistance. Comparative genomic analysis showed close relatedness to European isolates, representing the first genomic documentation of cc175 in Tunisia. This case underscores the value of genomic analysis for detecting emerging antimicrobial resistance and monitoring unusual meningococcal lineages in adult patients.
The prognostic utility of plasma endotoxemia, marked by elevated lipopolysaccharide (LPS) and often associated with gut barrier dysfunction, remains undefined in acute ischemic stroke (AIS) patients with type 2 diabetes....The prognostic utility of plasma endotoxemia, marked by elevated lipopolysaccharide (LPS) and often associated with gut barrier dysfunction, remains undefined in acute ischemic stroke (AIS) patients with type 2 diabetes. In this single-center prospective cohort of 300 AIS patients with diabetes, we measured early admission plasma LPS and assessed its correlation with stroke severity and inflammatory markers, and its independent association with 90-day unfavorable functional outcome (modified Rankin Scale 3-6). Compared to the good outcome group, patients with poor outcomes had significantly higher LPS levels. Log-transformed LPS levels positively correlated with baseline NIHSS score, high-sensitivity C-reactive protein, and white blood cell count. After multivariable adjustment for age, NIHSS, HbA1c, atrial fibrillation, estimated glomerular filtration rate, and other covariates, each standard deviation increase in log-LPS was independently associated with an increased risk of 90-day unfavorable outcome (odds ratio 1.86, 95% CI 1.39-2.48). A clear dose-response relationship was observed, with the risk of poor outcome and mortality rising across LPS quartiles. Adding LPS to a basic clinical prediction model improved the area under the curve from 0.79 to 0.83, enhanced risk reclassification, and provided greater net clinical benefit across a range of decision thresholds. In conclusion, early admission plasma endotoxemia is an independent predictor of 90-day functional outcome in AIS patients with diabetes and improves conventional risk stratification. This finding positions LPS as a clinically accessible biomarker that is associated with poor recovery in acute ischemic stroke.
Stenotrophomonas maltophilia is an opportunistic pathogen primarily associated with hospital-acquired infections, particularly in individuals who are immunocompromised. S. maltophilia infections pose a significant clinic...Stenotrophomonas maltophilia is an opportunistic pathogen primarily associated with hospital-acquired infections, particularly in individuals who are immunocompromised. S. maltophilia infections pose a significant clinical challenge due to the bacterium's sophisticated intrinsic and acquired mechanisms, which render it naturally multidrug resistant. The management of such infections is thus difficult, as the availability of effective therapeutic agents is limited. Antibiotic therapy options include co-trimoxazole, minocycline, tigecycline, levofloxacin, cefiderocol, and ceftazidime-avibactam. Co-trimoxazole, which comprises a synergistic combination of trimethoprim and sulfamethoxazole, remains the recommended first-line therapy for S. maltophilia infections. In this review, we critically evaluate the current evidence on the efficacy of co-trimoxazole against S. maltophilia. The present global prevalence of co-trimoxazole resistance in S. maltophilia clinical isolates varies from <5% to approximately 44%, raising concerns about its long-term reliability. Resistance to co-trimoxazole arises through several mechanisms. Horizontal gene transfer can introduce sul genes, which encode sulfonamide-insensitive dihydropteroate synthase, or dfrA genes, which encode trimethoprim-insensitive dihydrofolate reductase. Both enzymes function within the folate biosynthesis pathway, and their expression directly confers co-trimoxazole resistance. S. maltophilia can also acquire co-trimoxazole resistance through genetic mutations. The overexpression of efflux systems such as SmeVWX and SmeDEF, contributes to high-level resistance to co-trimoxazole, often triggered by mutations in the transcriptional regulators. Resistant strains frequently emerge due to improper antimicrobial use, as environmental antibiotic residues can act as selection pressure, facilitating the emergence and persistence of resistant strains. Despite these challenges, co-trimoxazole continues to demonstrate substantial clinical utility. It remains effective in many settings, either as monotherapy or in combination with other antibiotics such as minocycline, tigecycline, cefiderocol, or levofloxacin, and often achieves favorable outcomes.
Lack of standardized criteria for discontinuing contact precautions (CP) in patients colonized or infected with multidrug-resistant bacteria (MDRB) can prolong isolation and strain healthcare resources. This retrospectiv...Lack of standardized criteria for discontinuing contact precautions (CP) in patients colonized or infected with multidrug-resistant bacteria (MDRB) can prolong isolation and strain healthcare resources. This retrospective cohort study aimed to assess the safety of a protocol-guided CP discontinuation strategy and identify risk factors for MDRB reacquisition. The study evaluated 88 adult patients under CP who met an institutional protocol for CP discontinuation between 2018 and 2023. The protocol required: no active infection; no antibiotic use in the preceding seven days; no drains or open wounds; no diarrhea; a negative culture from the initial site of MDRB identification; and a subsequent confirmatory negative screening (culture and/or PCR). Patients were followed for one year after CP discontinuation to assess MDRB reacquisition, defined as a new positive specimen for the same species. Potential risk factors for reacquisition were analyzed using multivariable Cox regression. At the one-year follow-up, MDRB reacquisition occurred in 17% (15/88) of patients. The reacquired pathogens included carbapenem-resistant Enterobacterales (9/50), methicillin-resistant Staphylococcus aureus (6/30), and vancomycin-resistant Enterococcus spp. (0/8). Independent risk factors for reacquisition were chronic obstructive pulmonary disease (HR 5.76, 95% CI 1.34-24.81), shorter duration of isolation (HR 0.98 per day, 95% CI 0.97-0.99), frequent hospitalizations (HR 1.75 per admission, 95% CI 1.07-2.88), and central venous catheterization (HR 13.04, 95% CI 2.63-64.69). Protocol-guided CP discontinuation was associated with a low rate of MDRB reacquisition and appears safe in appropriately selected patients. This approach may reduce unnecessary isolation in eligible patients, though high-risk individuals require closer monitoring.