Pub Date : 2025-12-01Epub Date: 2025-12-03DOI: 10.1016/j.ijmm.2025.151689
Zhengyu Luo , Yating Ning , Rongchen Dai , Ailifeire Ainiwaer , Yanhong Li , Ruike Zhang , Meng Xiao , Xiaoxi Wang , Yang Yang , Yuyan Huang , Dingding Li , Lingli Liu , Roujie Huang , Tingying Xu , Yingchun Xu , Zhiyong Liu , Li Zhang , Tianshu Sun
Fungal infections pose a growing global threat, particularly due to the emergence of multidrug-resistant pathogens. This study reports the first globally documented case of a Wickerhamomyces anomalus isolate (XN272) displaying dual high-level resistance to all tested azoles and echinocandins. Genomic analysis of the strain, which was isolated from a bloodstream infection in a 64-year-old male post-pancreatic surgery, identified two key resistance mechanisms: the azole target gene ERG11 harbored missense mutations (Y140H, K151R) and tandem copy number variations, while the echinocandin target gene FKS1 carried an F665S mutation. Transcriptomic profiling under antifungal exposure suggested an additional resistance mechanism, the upregulation of membrane-associated genes and efflux transporters (e.g., FLU1). Strain XN272 exhibited robust biofilm-forming capacity, a trait linked to reduced drug susceptibility. Despite its resistant phenotype, virulence assessments in immunosuppressed mice showed comparable tissue colonization and clearance rates to strain ATCC 8168. The discovery of pan-azole and pan-echinocandin resistance in W. anomalus highlights the expanding landscape of antifungal resistance and its clinical management challenges.
{"title":"A pan-azole and pan-echinocandin resistant Wickerhamomyces anomalus isolate causing bloodstream infection: ERG11Y140F, K151R with copy number variation and FKS1 F665S mutation","authors":"Zhengyu Luo , Yating Ning , Rongchen Dai , Ailifeire Ainiwaer , Yanhong Li , Ruike Zhang , Meng Xiao , Xiaoxi Wang , Yang Yang , Yuyan Huang , Dingding Li , Lingli Liu , Roujie Huang , Tingying Xu , Yingchun Xu , Zhiyong Liu , Li Zhang , Tianshu Sun","doi":"10.1016/j.ijmm.2025.151689","DOIUrl":"10.1016/j.ijmm.2025.151689","url":null,"abstract":"<div><div>Fungal infections pose a growing global threat, particularly due to the emergence of multidrug-resistant pathogens. This study reports the first globally documented case of a <em>Wickerhamomyces anomalus</em> isolate (XN272) displaying dual high-level resistance to all tested azoles and echinocandins. Genomic analysis of the strain, which was isolated from a bloodstream infection in a 64-year-old male post-pancreatic surgery, identified two key resistance mechanisms: the azole target gene <em>ERG11</em> harbored missense mutations (Y140H, K151R) and tandem copy number variations, while the echinocandin target gene <em>FKS1</em> carried an F665S mutation. Transcriptomic profiling under antifungal exposure suggested an additional resistance mechanism, the upregulation of membrane-associated genes and efflux transporters (e.g., <em>FLU1</em>). Strain XN272 exhibited robust biofilm-forming capacity, a trait linked to reduced drug susceptibility. Despite its resistant phenotype, virulence assessments in immunosuppressed mice showed comparable tissue colonization and clearance rates to strain ATCC 8168. The discovery of pan-azole and pan-echinocandin resistance in <em>W. anomalus</em> highlights the expanding landscape of antifungal resistance and its clinical management challenges.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151689"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-20DOI: 10.1016/j.ijmm.2025.151686
Ying Wang , Zhihan Xiao , Huimin Xi , Qing Zhu , Peng Liu , Rui Zhao
Objectives
This study aimed to characterize the molecular epidemiology, antimicrobial resistance, virulence profiles, and clinical outcomes of Methicillin-resistant Staphylococcus aureus (MRSA) infections among intensive care unit (ICU) patients in southern China.
Methods
A total of 104 non-duplicate MRSA isolates were collected from ICU patients at a tertiary hospital between 2021 and 2024. Whole-genome sequencing was used to determine molecular characteristics. Antimicrobial susceptibility, biofilm formation, and hemolytic activity were conducted. Clinical data were analyzed to evaluate associations between MRSA lineages and patient outcomes.
Results
Eight clonal complexes and 16 sequence types were identified, with Clonal Complex (CC)5 (31.7 %), CC59 (20.2 %), and CC398 (18.3 %) being the most predominant. The dominant clones, namely CC5-ST5-SCCmec II-agr II, CC398-ST398-SCCmec V-agr I, and CC59-ST59-SCCmec IV-agr I, each exhibited distinct phylogenetic clustering patterns and resistance patterns. Notably, ST764, a variant of ST5, showed extensive multidrug resistance and robust biofilm-forming capacity, while ST59 isolates displayed the highest hemolytic activity. ST5 and ST764 exhibited the broadest resistance profiles. Virulence genes hla, psmα1–4 and psmβ1 present in all isolates, while tst was more frequent in CC5 and associated with higher 30-day death rate (P = 0.038). CC5 infections were linked to worse outcomes, with a death rate of 45.5 %. Renal insufficiency (P < 0.001) and malignancy (P = 0.011) were independent predictors of 30-day death rate.
Conclusion
ICU-derived MRSA isolates in southern China display considerable molecular diversity and varying resistance and virulence profiles. CC5, especially ST764, is associated with multidrug resistance and poor clinical outcomes, highlighting the need for enhanced infection control in ICUs.
{"title":"Clinical characteristics and whole-genome analysis of methicillin-resistant Staphylococcus aureus in ICU patients from a tertiary hospital in southern China","authors":"Ying Wang , Zhihan Xiao , Huimin Xi , Qing Zhu , Peng Liu , Rui Zhao","doi":"10.1016/j.ijmm.2025.151686","DOIUrl":"10.1016/j.ijmm.2025.151686","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aimed to characterize the molecular epidemiology, antimicrobial resistance, virulence profiles, and clinical outcomes of Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) infections among intensive care unit (ICU) patients in southern China.</div></div><div><h3>Methods</h3><div>A total of 104 non-duplicate MRSA isolates were collected from ICU patients at a tertiary hospital between 2021 and 2024. Whole-genome sequencing was used to determine molecular characteristics. Antimicrobial susceptibility, biofilm formation, and hemolytic activity were conducted. Clinical data were analyzed to evaluate associations between MRSA lineages and patient outcomes.</div></div><div><h3>Results</h3><div>Eight clonal complexes and 16 sequence types were identified, with Clonal Complex (CC)5 (31.7 %), CC59 (20.2 %), and CC398 (18.3 %) being the most predominant. The dominant clones, namely CC5-ST5-SCC<em>mec</em> II-<em>agr</em> II, CC398-ST398-SCC<em>mec</em> V-<em>agr</em> I, and CC59-ST59-SCC<em>mec</em> IV-<em>agr</em> I, each exhibited distinct phylogenetic clustering patterns and resistance patterns. Notably, ST764, a variant of ST5, showed extensive multidrug resistance and robust biofilm-forming capacity, while ST59 isolates displayed the highest hemolytic activity. ST5 and ST764 exhibited the broadest resistance profiles. Virulence genes <em>hla, psmα1–4</em> and <em>psmβ1</em> present in all isolates, while <em>tst</em> was more frequent in CC5 and associated with higher 30-day death rate (<em>P</em> = 0.038). CC5 infections were linked to worse outcomes, with a death rate of 45.5 %. Renal insufficiency (<em>P</em> < 0.001) and malignancy (<em>P</em> = 0.011) were independent predictors of 30-day death rate.</div></div><div><h3>Conclusion</h3><div>ICU-derived MRSA isolates in southern China display considerable molecular diversity and varying resistance and virulence profiles. CC5, especially ST764, is associated with multidrug resistance and poor clinical outcomes, highlighting the need for enhanced infection control in ICUs.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151686"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-23DOI: 10.1016/j.ijmm.2025.151676
Leonie H. Aldejohann , Joerg Steinmann , Tamara Ruegamer , Ronny Martin , Nadja Thielemann , Grit Walther , Oliver Kurzai , Alexander M. Aldejohann
Background
COVID-19-associated-pulmonary-aspergillosis (CAPA) is a severe superinfection mostly affecting critically ill COVID-19 patients. Early diagnosis and clinical management of CAPA remain major clinical challenges.
Here, we evaluated different approaches to classify culture-positive CAPA at its peak season, assessed incidence and mortality, identified risk factors and analysed clinical and laboratory CAPA-management of three German tertiary care hospitals.
Methods
A retrospective multi-center analysis was performed. Inclusion criteria were SARS-CoV-2-positivity, Aspergillus-culture-positivity of lower respiratory tract specimen and ARDS. Cases were primarily classified according to ECMM/ISHAM-criteria. Species-ID was confirmed by each center. Susceptibility was assessed by EUCAST-microdilution or VIPcheck-screening. Statistical analysis revealed mortality affecting factors.
Results
95 culture-positive CAPA cases were classified as possible (36/95) or probable (59/95) by ECMM/ISHAM; 54 probable cases matched 2 or 3 additional classifications. Incidence rates were higher in ICU (2020/21: 1.56 %/2.13 % non-ICU vs. 5.14 %/6.77 % ICU). A. fumigatus was the most abundant species (93 %; (88/95)). Most patients received steroids to treat COVID-19-ARDS and required respiratory support (steroids: 71 % (67/95); intubated patients 52 % (49/95); ECMO (48 % (46/95)). Retrospective evaluation showed adherence to ECMM/ISHAM antifungal therapy guideline in 71 % (67/95). Case fatality rate was 60 % (57/95). A significant association between GM indices > 3 in respiratory fluid or nicotine abuse (p = 0.035 FE, OR=0.252, 95 % CI=0.066–0.986) and mortality was observed in univariate analysis. Convalescent plasma therapy was significantly associated with mortality reduction in uni- and multivariate analysis (p = 0.020).
Conclusion
Our data reveal regional differences in prevalence, diagnosis, and treatment of culture-positive CAPA in Germany. We could identify new factors affecting survival or mortality.
{"title":"Culture-positive COVID-19-associated pulmonary aspergillosis (CAPA) in Germany","authors":"Leonie H. Aldejohann , Joerg Steinmann , Tamara Ruegamer , Ronny Martin , Nadja Thielemann , Grit Walther , Oliver Kurzai , Alexander M. Aldejohann","doi":"10.1016/j.ijmm.2025.151676","DOIUrl":"10.1016/j.ijmm.2025.151676","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19-associated-pulmonary-aspergillosis (CAPA) is a severe superinfection mostly affecting critically ill COVID-19 patients. Early diagnosis and clinical management of CAPA remain major clinical challenges.</div><div>Here, we evaluated different approaches to classify culture-positive CAPA at its peak season, assessed incidence and mortality, identified risk factors and analysed clinical and laboratory CAPA-management of three German tertiary care hospitals.</div></div><div><h3>Methods</h3><div>A retrospective multi-center analysis was performed. Inclusion criteria were SARS-CoV-2-positivity, <em>Aspergillus</em>-culture-positivity of lower respiratory tract specimen and ARDS. Cases were primarily classified according to ECMM/ISHAM-criteria. Species-ID was confirmed by each center. Susceptibility was assessed by EUCAST-microdilution or VIPcheck-screening. Statistical analysis revealed mortality affecting factors.</div></div><div><h3>Results</h3><div>95 culture-positive CAPA cases were classified as possible (36/95) or probable (59/95) by ECMM/ISHAM; 54 probable cases matched 2 or 3 additional classifications. Incidence rates were higher in ICU (2020/21: 1.56 %/2.13 % non-ICU vs. 5.14 %/6.77 % ICU). <em>A. fumigatus</em> was the most abundant species (93 %; (88/95)). Most patients received steroids to treat COVID-19-ARDS and required respiratory support (steroids: 71 % (67/95); intubated patients 52 % (49/95); ECMO (48 % (46/95)). Retrospective evaluation showed adherence to ECMM/ISHAM antifungal therapy guideline in 71 % (67/95). Case fatality rate was 60 % (57/95). A significant association between GM indices > 3 in respiratory fluid or nicotine abuse (p = 0.035 FE, OR=0.252, 95 % CI=0.066–0.986) and mortality was observed in univariate analysis. Convalescent plasma therapy was significantly associated with mortality reduction in uni- and multivariate analysis (p = 0.020).</div></div><div><h3>Conclusion</h3><div>Our data reveal regional differences in prevalence, diagnosis, and treatment of culture-positive CAPA in Germany. We could identify new factors affecting survival or mortality.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151676"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-10-26DOI: 10.1016/j.ijmm.2025.151681
Francesca McDonagh , Aneta Kovarova , Anna Tumeo , Andy O’Connor , Niamh McEvoy , Aneesa Mangalam Lonappan , Kasthuri Venkateswaran , Elaine K. Murray , Brian Hallahan , Georgios Miliotis
Objectives
This study aims to generate the first complete genome of Pantoea septica and provide a thorough genomic characterisation of this under-documented species. The study seeks to enhance understanding of P. septica, clarifying features relevant to opportunistic infection in vulnerable cohorts.
Methods
P. septica GABEPS69 was an opportunistic coloniser isolated from the saliva of a patient prescribed the antipsychotic clozapine, leading to a dysbiotic oral microbiome. A hybrid sequencing approach yielded a closed genome comprising a 4.1 Mb chromosome and six plasmids. Phenotypic susceptibility was determined by disk-diffusion and minimum inhibitory concentration (MIC) assays. Its chromosomal and plasmidic content was bioinformatically analysed alongside all canonical GenBank available P. septica genomes and the type strains of taxonomic neighbours Pantoea piersonii and "Pantoea latae", with focus on virulence-factors (VFs), antimicrobial-resistance-genes (ARGs), metal-resistance-genes (MRGs) and biosynthetic gene clusters.
Results
GABEPS69 exhibited a narrow resistance spectrum, displaying resistance to the third-generation cephalosporin cefpodoxime. Plasmid pGABEPS69_1 harboured an aerobactin pathogenicity island homologue; a locus implicated in enhanced virulence, that was also identified across most other P. septica genomes and in the closely related human-pathogen Pantoea piersonii. A conserved chromosomal class-A β-lactamase homologue was also identified. Additionally, a universal presence of bioactive thiopeptide biosynthetic-gene-clusters was observed in P. septica genomes, suggesting a potential role in microbiome modulation.
Conclusion
This study presents a first complete genome of P. septica, revealing its genomic architecture, resistance, and virulence potential. Detailed plasmid analysis and comparative genomics enhance our understanding of the species clinical relevance and microbiome-modulating capacity. These findings motivate surveillance of transient oral microbiota in at-risk populations, including patients receiving clozapine.
{"title":"Complete genome and comparative genomic analysis of cefpodoxime resistant Pantoea septica strain GABEPS69 isolated from saliva of a patient diagnosed with treatment resistant schizophrenia","authors":"Francesca McDonagh , Aneta Kovarova , Anna Tumeo , Andy O’Connor , Niamh McEvoy , Aneesa Mangalam Lonappan , Kasthuri Venkateswaran , Elaine K. Murray , Brian Hallahan , Georgios Miliotis","doi":"10.1016/j.ijmm.2025.151681","DOIUrl":"10.1016/j.ijmm.2025.151681","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to generate the first complete genome of <em>Pantoea septica</em> and provide a thorough genomic characterisation of this under-documented species. The study seeks to enhance understanding of <em>P. septica,</em> clarifying features relevant to opportunistic infection in vulnerable cohorts<em>.</em></div></div><div><h3>Methods</h3><div><em>P. septica</em> GABEPS69 was an opportunistic coloniser isolated from the saliva of a patient prescribed the antipsychotic clozapine, leading to a dysbiotic oral microbiome. A hybrid sequencing approach yielded a closed genome comprising a 4.1 Mb chromosome and six plasmids. Phenotypic susceptibility was determined by disk-diffusion and minimum inhibitory concentration (MIC) assays. Its chromosomal and plasmidic content was bioinformatically analysed alongside all canonical GenBank available <em>P. septica</em> genomes and the type strains of taxonomic neighbours <em>Pantoea piersonii</em> and \"<em>Pantoea latae</em>\", with focus on virulence-factors (VFs), antimicrobial-resistance-genes (ARGs), metal-resistance-genes (MRGs) and biosynthetic gene clusters.</div></div><div><h3>Results</h3><div>GABEPS69 exhibited a narrow resistance spectrum, displaying resistance to the third-generation cephalosporin cefpodoxime. Plasmid pGABEPS69_1 harboured an aerobactin pathogenicity island homologue; a locus implicated in enhanced virulence, that was also identified across most other <em>P. septica</em> genomes and in the closely related human-pathogen <em>Pantoea piersonii</em>. A conserved chromosomal class-A β-lactamase homologue was also identified. Additionally, a universal presence of bioactive thiopeptide biosynthetic-gene-clusters was observed in <em>P. septica</em> genomes, suggesting a potential role in microbiome modulation.</div></div><div><h3>Conclusion</h3><div>This study presents a first complete genome of <em>P. septica</em>, revealing its genomic architecture, resistance, and virulence potential. Detailed plasmid analysis and comparative genomics enhance our understanding of the species clinical relevance and microbiome-modulating capacity. These findings motivate surveillance of transient oral microbiota in at-risk populations, including patients receiving clozapine.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151681"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-06DOI: 10.1016/j.ijmm.2025.151672
Ebrahim Golmakani , Roya Sadidi , Seyed Ahmad Hashemi , Ali Haghbin , Amir Azimian
Introduction
Methicillin-resistant Staphylococcus aureus (MRSA) remains a global health threat, with livestock-associated (LA-)MRSA ST398/t011 emerging in regions with human-animal contact. This study reports the first detection of ST398/t011 in clinical isolates from Bojnurd, northeastern Iran, alongside the hospital-associated ST239/t037 clone.
Methods
From January to April 2025, 242 clinical samples from Imam Reza Hospital were screened for S. aureus. MRSA isolates underwent antimicrobial susceptibility testing (CLSI M100-2023) and molecular characterization (mecA, mecC, vanA, cfr, PVL, tsst, sec, hla; SCCmec, agr, spa typing, MLST).
Results
Of 32 positive cultures, 7 MRSA isolates were identified (ST398/t011 [n = 4]; ST239/t037 [n = 3]). All harbored mecA and exhibited resistance to β-lactams, clindamycin, and gentamicin but remained susceptible to vancomycin/linezolid. The PVL gene was detected in one ST398/t011 isolate. ST398/t011 carried SCCmec V and agr I, while ST239/t037 had SCCmec III. Isolates were recovered from wound (n = 3), blood (n = 2), eye (n = 1), and urine (n = 1) samples, with patients aged 6–48 years.
Discussion
This first report of LA-MRSA ST398/t011 in northeastern Iran highlights potential zoonotic transmission risks in this agricultural region. Co-detection of PVL in ST398/t011 and multidrug-resistant ST239/t037 underscores the need for enhanced surveillance. Limitations include the small sample size, but findings warrant further One Health investigations to assess reservoirs and transmission dynamics.
{"title":"Multiple isolation of ST398/t011 MRSA from patients in the first half of 2025 in Imam Reza Hospital, Bojnurd, North Eastern Iran","authors":"Ebrahim Golmakani , Roya Sadidi , Seyed Ahmad Hashemi , Ali Haghbin , Amir Azimian","doi":"10.1016/j.ijmm.2025.151672","DOIUrl":"10.1016/j.ijmm.2025.151672","url":null,"abstract":"<div><h3>Introduction</h3><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) remains a global health threat, with livestock-associated (LA-)MRSA ST398/t011 emerging in regions with human-animal contact. This study reports the first detection of ST398/t011 in clinical isolates from Bojnurd, northeastern Iran, alongside the hospital-associated ST239/t037 clone.</div></div><div><h3>Methods</h3><div>From January to April 2025, 242 clinical samples from Imam Reza Hospital were screened for <em>S. aureus</em>. MRSA isolates underwent antimicrobial susceptibility testing (CLSI M100-2023) and molecular characterization (<em>mecA</em>, <em>mecC</em>, <em>vanA</em>, <em>cfr</em>, <em>PVL</em>, <em>tsst</em>, <em>sec</em>, <em>hla</em>; SCC<em>mec</em>, <em>agr</em>, <em>spa</em> typing, MLST).</div></div><div><h3>Results</h3><div>Of 32 positive cultures, 7 MRSA isolates were identified (ST398/t011 [n = 4]; ST239/t037 [n = 3]). All harbored <em>mecA</em> and exhibited resistance to β-lactams, clindamycin, and gentamicin but remained susceptible to vancomycin/linezolid. The <em>PVL</em> gene was detected in one ST398/t011 isolate. ST398/t011 carried SCC<em>mec</em> V and <em>agr</em> I, while ST239/t037 had SCC<em>mec</em> III. Isolates were recovered from wound (n = 3), blood (n = 2), eye (n = 1), and urine (n = 1) samples, with patients aged 6–48 years.</div></div><div><h3>Discussion</h3><div>This first report of LA-MRSA ST398/t011 in northeastern Iran highlights potential zoonotic transmission risks in this agricultural region. Co-detection of <em>PVL</em> in ST398/t011 and multidrug-resistant ST239/t037 underscores the need for enhanced surveillance. Limitations include the small sample size, but findings warrant further One Health investigations to assess reservoirs and transmission dynamics.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151672"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-13DOI: 10.1016/j.ijmm.2025.151684
Muhammad Tahir Khan , Chendi Zhu , Arwa Omar Al Khatib , Dalal Sulaiman Alshaya , Ahmed A. Al-Qahtani , Irfan Ahmad , Taane G. Clark
Introduction
Understanding the distribution and prevalence of different M. tuberculosis lineages can help public health authorities and researchers track the spread of tuberculosis (TB). Some lineages are thought to be more virulent, transmissible, and prone to drug resistance. Here, we sought to find the major lineages and sublineages of M. tuberculosis circulating in Pakistan. Methods: A total of 396 whole-genome sequencing datasets were retrieved from NCBI and TB research centers. Results: In the current study, only four lineages and 21 sublineages have been detected in 396 genomic isolates in which lineages 3 (n = 274/396, 69.19 %) was the predominant, followed by lineage 4 (77/396, 19.4 %), lineage 2 (31/396, 7.8 %), and lineage 1 (14/396, 3.5 %). Lineage 3 was the most common, in which sublineage 3.1.1 (n = 254/274, 93.79 %) was dominant, followed by sublineage 3.1.2.1 (n = 11/274, 4 %) and 3.1.2 (n = 8/274, 2.9 %). 8 sublineages are likely reported for the first time in Pakistan based on current genomic surveillance including sublineage 3.1.2.1 (n = 11/274, 4 %). There were 14 sublineages in lineage 4, of which sublineage L4.5 (23/77, 29.8 %) was the most common, followed by sublineage 4.9 (22/77, 28.5 %). Conclusion: Collectively, these observations highlight Lineage 3’s ability to acquire first-line drug resistance continued transmission. Its predominance in the current study highlights the urgent need for lineage-specific diagnostics, enhanced drug susceptibility testing and tailored therapeutic regimens. The detection of diverse Mtb sublineages, including L3.1.2.1 and various sublineages of L4 (e.g., 4.1.1.1, 4.1.2.1, 4.3.4.2, and 4.6.2.2), signifies advancement in understanding the genetic landscape of TB in the region.
{"title":"Emergence of novel sublineages of Mycobacterium tuberculosis in Pakistan","authors":"Muhammad Tahir Khan , Chendi Zhu , Arwa Omar Al Khatib , Dalal Sulaiman Alshaya , Ahmed A. Al-Qahtani , Irfan Ahmad , Taane G. Clark","doi":"10.1016/j.ijmm.2025.151684","DOIUrl":"10.1016/j.ijmm.2025.151684","url":null,"abstract":"<div><h3>Introduction</h3><div>Understanding the distribution and prevalence of different <em>M. tuberculosis</em> lineages can help public health authorities and researchers track the spread of tuberculosis (TB). Some lineages are thought to be more virulent, transmissible, and prone to drug resistance. Here, we sought to find the major lineages and sublineages of <em>M. tuberculosis</em> circulating in Pakistan. Methods: A total of 396 whole-genome sequencing datasets were retrieved from NCBI and TB research centers. Results: In the current study, only four lineages and 21 sublineages have been detected in 396 genomic isolates in which lineages 3 (n = 274/396, 69.19 %) was the predominant, followed by lineage 4 (77/396, 19.4 %), lineage 2 (31/396, 7.8 %), and lineage 1 (14/396, 3.5 %). Lineage 3 was the most common, in which sublineage 3.1.1 (n = 254/274, 93.79 %) was dominant, followed by sublineage 3.1.2.1 (n = 11/274, 4 %) and 3.1.2 (n = 8/274, 2.9 %). 8 sublineages are likely reported for the first time in Pakistan based on current genomic surveillance including sublineage 3.1.2.1 (n = 11/274, 4 %). There were 14 sublineages in lineage 4, of which sublineage L4.5 (23/77, 29.8 %) was the most common, followed by sublineage 4.9 (22/77, 28.5 %). Conclusion: Collectively, these observations highlight Lineage 3’s ability to acquire first-line drug resistance continued transmission. Its predominance in the current study highlights the urgent need for lineage-specific diagnostics, enhanced drug susceptibility testing and tailored therapeutic regimens. The detection of diverse Mtb sublineages, including L3.1.2.1 and various sublineages of L4 (e.g., 4.1.1.1, 4.1.2.1, 4.3.4.2, and 4.6.2.2), signifies advancement in understanding the genetic landscape of TB in the region.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151684"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145551654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-09-16DOI: 10.1016/j.ijmm.2025.151674
Zia Ud Din , Farman Ullah , Anwar Sheed Khan , Sajjad Ahmad , Azra , Aiman Waheed , Noor Muhmmad , Fawad Ali , Farhad Ali Khattak , Gulab Fatima Rani , Otavio Cabral-Marques , Ihtisham Ul Haq , Muhammad Riaz , Jody E. Phelan , Susana Campino , Taj Ali Khan , Taane G. Clark
Background
Tuberculosis (TB), caused by bacteria of the Mycobacterium tuberculosis complex (MTBC), remains a global health challenge, exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.
Objectives
This study employs whole-genome sequencing (WGS) to characterise genetic mutations associated with pyrazinamide (PZA) and fluoroquinolone (FQ) resistance in MDR-TB isolates from KPK.
Methodology
MDR and pre-XDR TB samples were collected and processed at the Provincial Tuberculosis Reference Laboratory under Biosafety Level III conditions. Samples underwent microscopy, GeneXpert MTB/RIF assay, culture, and drug susceptibility testing. DNA was extracted from positive cultures and subjected to WGS. Bioinformatics tools were used to analyse sequencing data, identify resistance-associated mutations, and assess genetic diversity among isolates.
Results
Out of the 78 MTBC isolates analysed, 67 (85.9 %) were identified as MDR-TB, with 48 categorized as pre-XDR, while 11 were drug-susceptible. The isolates predominantly came from young patients (mean age: 29.5 years, SD ±12.64), with a higher proportion of female patients (61.53 %). Mutations in the pncA gene, associated with PZA resistance, were identified in 51 isolates. Resistance to fluoroquinolones was linked to mutations in the gyrA and gyrB genes in 48 isolates. WGS confirmed PZA resistance in 51 isolates, 39 (76.47 %) of which also exhibited FQ resistance.
Conclusion
Phylogenetic analysis revealed that Lineage 3 (L3) was predominant (58.97 %), followed by L4, L2, and L1 strains. The clustering of drug-resistant strains within L3 suggests ongoing localized transmission. These findings underscore the urgent need for targeted interventions, including enhanced molecular surveillance and tailored treatment strategies, to combat MDR-TB in KPK.
{"title":"Genomic insights into pyrazinamide and fluoroquinolone resistance in multidrug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan","authors":"Zia Ud Din , Farman Ullah , Anwar Sheed Khan , Sajjad Ahmad , Azra , Aiman Waheed , Noor Muhmmad , Fawad Ali , Farhad Ali Khattak , Gulab Fatima Rani , Otavio Cabral-Marques , Ihtisham Ul Haq , Muhammad Riaz , Jody E. Phelan , Susana Campino , Taj Ali Khan , Taane G. Clark","doi":"10.1016/j.ijmm.2025.151674","DOIUrl":"10.1016/j.ijmm.2025.151674","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculosis (TB), caused by bacteria of the <em>Mycobacterium tuberculosis</em> complex (MTBC), remains a global health challenge, exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains.</div></div><div><h3>Objectives</h3><div>This study employs whole-genome sequencing (WGS) to characterise genetic mutations associated with pyrazinamide (PZA) and fluoroquinolone (FQ) resistance in MDR-TB isolates from KPK.</div></div><div><h3>Methodology</h3><div>MDR and pre-XDR TB samples were collected and processed at the Provincial Tuberculosis Reference Laboratory under Biosafety Level III conditions. Samples underwent microscopy, GeneXpert MTB/RIF assay, culture, and drug susceptibility testing. DNA was extracted from positive cultures and subjected to WGS. Bioinformatics tools were used to analyse sequencing data, identify resistance-associated mutations, and assess genetic diversity among isolates.</div></div><div><h3>Results</h3><div>Out of the 78 MTBC isolates analysed, 67 (85.9 %) were identified as MDR-TB, with 48 categorized as pre-XDR, while 11 were drug-susceptible. The isolates predominantly came from young patients (mean age: 29.5 years, SD ±12.64), with a higher proportion of female patients (61.53 %). Mutations in the <em>pncA</em> gene, associated with PZA resistance, were identified in 51 isolates. Resistance to fluoroquinolones was linked to mutations in the <em>gyrA</em> and <em>gyrB</em> genes in 48 isolates. WGS confirmed PZA resistance in 51 isolates, 39 (76.47 %) of which also exhibited FQ resistance.</div></div><div><h3>Conclusion</h3><div>Phylogenetic analysis revealed that Lineage 3 (L3) was predominant (58.97 %), followed by L4, L2, and L1 strains. The clustering of drug-resistant strains within L3 suggests ongoing localized transmission. These findings underscore the urgent need for targeted interventions, including enhanced molecular surveillance and tailored treatment strategies, to combat MDR-TB in KPK.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151674"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acinetobacter baumannii (AB) is the most frequently isolated nosocomial pathogen, but severe infections by A. pittii, A. ursingii, and A. bereziniae are increasing. This study investigated the distribution and antibiotic resistance of Acinetobacter spp. strains from various clinical specimens.
Methods
Data were collected between 2021–2023 from clinical samples of hospitalized and outpatient individuals in southern Poland. Strains were identified using MALDI-TOF Biotyper, and antibiotic susceptibility was tested with the MIDITECH-Analyzer system. Statistical analyses were conducted using IBM SPSS Statistics.
Results
Among 1507 isolated Acinetobacter strains, 951 (63.1 %) were AB, while 556 (36.9 %) represented 27 non-AB species. Most isolates (73.6 %) came from outpatients, while 26.4 % were from hospitalized patients. A. ursingii (30.2 %), A. pittii (20.6 %), and A. junii (13 %) were the most common non-AB species. A. bereziniae, A. calcoaceticus, and A. proteolyticus were more frequently found in hospitalized patients. Non-AB species dominated in clinical specimens from genitourinary tract (87 %), whereas AB was more common in clinical specimens from invasive sites. Nearly all strains were non-susceptible to ciprofloxacin (98.4 %), with lower resistance rates to ampicillin/sulbactam (11.1 %), trimethoprim/sulfamethoxazole (5.8 %), gentamicin (2.9 %), amikacin (2.5 %), meropenem (1.6 %), and colistin (1.6 %). A. bereziniae showed frequently resistance to carbapenems, aminoglycosides, and trimethoprim/sulfamethoxazole. Colistin resistance was observed in A. ursingii and A. pittii.
Conclusions
While AB accounted for 63.1 % of isolates, non-AB species were common, particularly in clinical specimens from genitourinary tract and from skin and wound. Emerging hospital-acquired infections by species like A. pittii underline the need for vigilant monitoring. The high resistance to ciprofloxacin and low but noticeable resistance to carbapenems and colistin highlights the importance of early detection and resistance surveillance to prevent the spread of resistant strains.
{"title":"Distribution and antimicrobial resistance of Acinetobacter spp. isolated from different types of clinical specimens from hospitalized patients and outpatients in Poland","authors":"Tomasz Kasperski , Monika Pobiega , Monika Pomorska-Wesołowska , Wiktoria Papuga , Agnieszka Chmielarczyk","doi":"10.1016/j.ijmm.2025.151685","DOIUrl":"10.1016/j.ijmm.2025.151685","url":null,"abstract":"<div><h3>Background</h3><div><em>Acinetobacter baumannii</em> (AB) is the most frequently isolated nosocomial pathogen, but severe infections by <em>A. pittii</em>, <em>A. ursingii</em>, and <em>A. bereziniae</em> are increasing. This study investigated the distribution and antibiotic resistance of Acinetobacter spp. strains from various clinical specimens.</div></div><div><h3>Methods</h3><div>Data were collected between 2021–2023 from clinical samples of hospitalized and outpatient individuals in southern Poland. Strains were identified using MALDI-TOF Biotyper, and antibiotic susceptibility was tested with the MIDITECH-Analyzer system. Statistical analyses were conducted using IBM SPSS Statistics.</div></div><div><h3>Results</h3><div>Among 1507 isolated Acinetobacter strains, 951 (63.1 %) were AB, while 556 (36.9 %) represented 27 non-AB species. Most isolates (73.6 %) came from outpatients, while 26.4 % were from hospitalized patients. <em>A. ursingii</em> (30.2 %), <em>A. pittii</em> (20.6 %), and <em>A. junii</em> (13 %) were the most common non-AB species. <em>A. bereziniae</em>, <em>A. calcoaceticus</em>, and <em>A. proteolyticus</em> were more frequently found in hospitalized patients. Non-AB species dominated in clinical specimens from genitourinary tract (87 %), whereas AB was more common in clinical specimens from invasive sites. Nearly all strains were non-susceptible to ciprofloxacin (98.4 %), with lower resistance rates to ampicillin/sulbactam (11.1 %), trimethoprim/sulfamethoxazole (5.8 %), gentamicin (2.9 %), amikacin (2.5 %), meropenem (1.6 %), and colistin (1.6 %). <em>A. bereziniae</em> showed frequently resistance to carbapenems, aminoglycosides, and trimethoprim/sulfamethoxazole. Colistin resistance was observed in <em>A. ursingii</em> and <em>A. pittii</em>.</div></div><div><h3>Conclusions</h3><div>While AB accounted for 63.1 % of isolates, non-AB species were common, particularly in clinical specimens from genitourinary tract and from skin and wound. Emerging hospital-acquired infections by species like <em>A. pittii</em> underline the need for vigilant monitoring. The high resistance to ciprofloxacin and low but noticeable resistance to carbapenems and colistin highlights the importance of early detection and resistance surveillance to prevent the spread of resistant strains.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151685"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01Epub Date: 2025-11-26DOI: 10.1016/j.ijmm.2025.151688
Florence Crombé , Frederic Auvray , Angela H.A.M. van Hoek , Bavo Verhaegen , Sigrid C.J. De Keersmaecker , Carolina Silva Nodari , Aurélie Cointe , Jacques Mainil , Caroline Willis , Gro S. Johannessen , Ralph Litjens , Joost Stassen , Denis Piérard
The increased detection of Shiga toxin-producing Escherichia coli (STEC) O113:H4 among human cases in Belgium questions the importance of this serotype as an emerging pathogen. However, detailed information focusing on serotype O113:H4 from human and non-human sources remains limited. We analysed a collection of 140 STEC O113:H4 isolates and their whole genomes, originating from animal hosts (cattle, deer, goats, and sheep), food, and humans, to determine their genetic relationship and assess key virulence genes. All STEC O113:H4 genomes lacked the locus of enterocyte effacement (LEE) and belonged to Pasteur Sequence Type (pST) 367 complex, dominated by pST367 (ehxA-, stx2d+) and pST1729 (ehxA+, stx2b+). Compared to stx2d+ isolates, stx2b+ isolates carried on median more virulence factors, which might thus contribute to enhanced pathogenicity. Besides, humans appear to be infected with distinct subgroups of STEC O113:H4 carrying distinct stx subtypes and originating from potentially different sources: deer, goats, and sheep for STEC carrying stx2b (alone or in combination with stx1c) and mainly cattle for STEC carrying stx2d. Our results call for improved understanding and continuous surveillance of emerging STEC O113:H4.
{"title":"Emergence and genetic heterogeneity of STEC O113:H4: insights from whole-genome sequences of isolates across human and non-human sources","authors":"Florence Crombé , Frederic Auvray , Angela H.A.M. van Hoek , Bavo Verhaegen , Sigrid C.J. De Keersmaecker , Carolina Silva Nodari , Aurélie Cointe , Jacques Mainil , Caroline Willis , Gro S. Johannessen , Ralph Litjens , Joost Stassen , Denis Piérard","doi":"10.1016/j.ijmm.2025.151688","DOIUrl":"10.1016/j.ijmm.2025.151688","url":null,"abstract":"<div><div>The increased detection of Shiga toxin-producing <em>Escherichia coli</em> (STEC) O113:H4 among human cases in Belgium questions the importance of this serotype as an emerging pathogen. However, detailed information focusing on serotype O113:H4 from human and non-human sources remains limited. We analysed a collection of 140 STEC O113:H4 isolates and their whole genomes, originating from animal hosts (cattle, deer, goats, and sheep), food, and humans, to determine their genetic relationship and assess key virulence genes. All STEC O113:H4 genomes lacked the locus of enterocyte effacement (LEE) and belonged to Pasteur Sequence Type (pST) 367 complex, dominated by pST367 (<em>ehxA</em><sup>-</sup>, <em>stx</em><sub>2d</sub><sup>+</sup>) and pST1729 (<em>ehxA</em><sup>+</sup>, <em>stx</em><sub>2b</sub><sup>+</sup>). Compared to <em>stx</em><sub>2d</sub><sup>+</sup> isolates, <em>stx</em><sub>2b</sub><sup>+</sup> isolates carried on median more virulence factors, which might thus contribute to enhanced pathogenicity. Besides, humans appear to be infected with distinct subgroups of STEC O113:H4 carrying distinct <em>stx</em> subtypes and originating from potentially different sources: deer, goats, and sheep for STEC carrying <em>stx</em><sub>2b</sub> (alone or in combination with <em>stx</em><sub>1c</sub>) and mainly cattle for STEC carrying <em>stx</em><sub>2d</sub>. Our results call for improved understanding and continuous surveillance of emerging STEC O113:H4.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151688"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In 2017, a large outbreak of Legionnaires' disease, involving 58 patients, occurred in a public bath facility in Hiroshima Prefecture, Japan. We analyzed 94 Legionella pneumophila strains isolated from patients and the public bath facility using molecular typing methods, including Pulsed-Field Gel Electrophoresis, sequence-based typing, multi-locus variable number tandem repeat analysis, and Whole-Genome Sequencing (WGS). Genotypes obtained using these molecular epidemiological typing methods were highly correlated with each other. L. pneumophila strains of various genotypes were isolated from the public bath facility, of which only ST2398 and ST2399 were isolated from patients. ST2398 and ST2399, isolated from patients, bath water, and swabs, derived from one common circulating system at the bath facility out of seven were found to be novel genotypes and a highly clonal genetic lineage by single nucleotide variant (SNV) analysis based on WGS. The result of haplotype network analysis based on SNVs showed that ST2398 and ST2399 differed only approximately 30–42 SNVs, and some environmental strains that differed by only 0–3 SNVs from patient strains were isolated. These results demonstrated that this outbreak was caused by L. pneumophila assigned to the ST2398 and ST2399 clades. We found that at least three patients were co-infected with different clusters of L. pneumophila serogroup 1. Our results show that several strains must be isolated from a single sample to consider the accumulation of mutations in water and co-infection when investigating outbreaks.
{"title":"A large outbreak investigation of Legionnaires’ disease associated with a public bath facility in Hiroshima, Japan, using PFGE, SBT, MLVA, and whole-genome sequencing","authors":"Takahiro Hiratsuka , Noriko Nakanishi , Hiroko Akita , Kanako Masuda , Shoko Komatsu , Ryohei Nomoto , Junko Amemura-Maekawa","doi":"10.1016/j.ijmm.2025.151680","DOIUrl":"10.1016/j.ijmm.2025.151680","url":null,"abstract":"<div><div>In 2017, a large outbreak of Legionnaires' disease, involving 58 patients, occurred in a public bath facility in Hiroshima Prefecture, Japan. We analyzed 94 <em>Legionella pneumophila</em> strains isolated from patients and the public bath facility using molecular typing methods, including Pulsed-Field Gel Electrophoresis, sequence-based typing, multi-locus variable number tandem repeat analysis, and Whole-Genome Sequencing (WGS). Genotypes obtained using these molecular epidemiological typing methods were highly correlated with each other. <em>L. pneumophila</em> strains of various genotypes were isolated from the public bath facility, of which only ST2398 and ST2399 were isolated from patients. ST2398 and ST2399, isolated from patients, bath water, and swabs, derived from one common circulating system at the bath facility out of seven were found to be novel genotypes and a highly clonal genetic lineage by single nucleotide variant (SNV) analysis based on WGS. The result of haplotype network analysis based on SNVs showed that ST2398 and ST2399 differed only approximately 30–42 SNVs, and some environmental strains that differed by only 0–3 SNVs from patient strains were isolated. These results demonstrated that this outbreak was caused by <em>L. pneumophila</em> assigned to the ST2398 and ST2399 clades. We found that at least three patients were co-infected with different clusters of <em>L. pneumophila</em> serogroup 1. Our results show that several strains must be isolated from a single sample to consider the accumulation of mutations in water and co-infection when investigating outbreaks.</div></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"321 ","pages":"Article 151680"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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