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@ARTICLE{LorenzoDiaz:281437,
      author       = {Lorenzo-Diaz, Fabian and Klassert, Tilman E and
                      Zubiria-Barrera, Cristina and Keles, Amelya and
                      Gonzalez-Carracedo, Mario and Hernandez, Mariano and
                      Slevogt, Hortense and Grünewald, Thomas},
      title        = {{C}lostridioides difficile evolution in a tertiary {G}erman
                      hospital through a retrospective genomic characterization.},
      journal      = {Infection},
      volume       = {53},
      number       = {5},
      issn         = {0300-8126},
      address      = {München},
      publisher    = {Urban $\&$ Vogel},
      reportid     = {DZNE-2025-01122},
      pages        = {2209 - 2218},
      year         = {2025},
      abstract     = {Clostridioides difficile is a major cause of
                      healthcare-associated infections, contributing to
                      significant morbidity and mortality. This study aimed to
                      investigate the genomic characteristics, antimicrobial
                      resistance (AMR) profiles, and temporal dynamics of C.
                      difficile strains isolated from hospitalized patients in a
                      German tertiary hospital over nearly two decades
                      (1997-2015).Whole-genome sequencing was performed on 46
                      toxigenic C. difficile isolates to determine sequence types
                      (STs) and phylogenetic relationships and these were compared
                      to national surveillance data on C. dificile. AMR profiling
                      was conducted to identify key resistance determinants at
                      genetic level while epsilometer minimum inhibitory
                      concentration (MIC) analyses were used to correlate genetic
                      resistance markers with phenotypic resistance. Longitudinal
                      antibiotic usage data were analysed to assess potential
                      associations with resistance profiles and strains
                      evolution.Five predominant STs were identified: ST1
                      $(30\%),$ ST54 $(24\%),$ ST3 $(22\%),$ ST11 $(11\%),$ and
                      ST37 $(4\%).$ Phylogenetic analysis showed that ST1
                      (ribotype 027) emerged as the dominant and persistent
                      lineage, replacing ST11 and ST54 over time. AMR profiling
                      detected several resistance genetic markers such as
                      CDD-1/CDD-2 (carbapenem resistance), ErmB
                      (macrolide-lincosamide-streptogramin B resistance/MLS
                      resistance), and mutations in gyrA (fluoroquinolone
                      resistance) and rpoB (rifampicin resistance). MIC analyses
                      confirmed high resistance rates to moxifloxacin $(87\%)$ and
                      rifampicin $(59\%),$ while susceptibility to fidaxomicin,
                      metronidazole, and vancomycin remained. The tetM gene,
                      associated with doxycycline resistance, declined as ST11 and
                      ST54 frequencies decreased. Longitudinal analysis revealed a
                      reduction in moxifloxacin resistance following its decreased
                      use, whereas increased doxycycline use paradoxically
                      correlated with reduced resistance.This study highlights the
                      dynamic strain evolution of C. difficile, reflecting
                      national trends in strain evolution. The findings emphasize
                      the strong correlation between epsilometer MIC values and
                      molecular resistance markers. This observation reinforces
                      the integration of genetic surveillance with antibiotic
                      stewardship in the clinical routine to effectively mitigate
                      CDI recurrence. Further research is needed to better
                      understand the complex interactions between antibiotic
                      exposure and strain evolution in hospital environments.},
      keywords     = {Clostridioides difficile: genetics / Clostridioides
                      difficile: drug effects / Clostridioides difficile:
                      classification / Clostridioides difficile: isolation $\&$
                      purification / Tertiary Care Centers / Humans / Germany:
                      epidemiology / Clostridium Infections: microbiology /
                      Clostridium Infections: epidemiology / Anti-Bacterial
                      Agents: pharmacology / Retrospective Studies / Microbial
                      Sensitivity Tests / Phylogeny / Whole Genome Sequencing /
                      Cross Infection: microbiology / Cross Infection:
                      epidemiology / Drug Resistance, Bacterial: genetics /
                      Evolution, Molecular / Genome, Bacterial / Male / Female /
                      Antibiotic resistance genes (Other) / CDI (Other) /
                      Clostridioides difficile (Other) / PaLoc (Other) / WGS
                      (Other) / Anti-Bacterial Agents (NLM Chemicals)},
      cin          = {AG Prüß},
      ddc          = {610},
      cid          = {I:(DE-2719)1810003},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40483626},
      doi          = {10.1007/s15010-025-02576-y},
      url          = {https://pub.dzne.de/record/281437},
}