1416. Comparison of multilocus variable-number tandem-repeat analysis (MLVA) and whole genome sequencing (WGS) to confirm or refute Clostridium difficile infection (CDI) case clusters
Session: Poster Abstract Session: Clostridium difficile
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • MLVA vs WGS poster IDWeek 2013 FINAL(resized for App) 23-09-13.pdf (646.1 kB)
  • Background:

    MLVA and WGS have increased discriminatory power for C. difficile epidemiology compared with most other typing methods, but notably these currently analyse different parts of the bacterial genome.  A formal performance comparison of MLVA vs WGS for assessment of suspected nosocomial CDI case clusters (sCDICCs) does not yet exist.

    Methods:

    Isolates from 61 sCDICCs, affecting 2-41 patients in 31 UK hospitals involving 11 PCR-ribotypes, underwent 7-locus MLVA and Illumina WGS. Cases from each sCDICC shared a common PCR-ribotype and close epidemiological links. MLVA and WGS data from all possible pairs of isolates within each sCDICC were compared. Results from both techniques were then used independently to establish investigation outcome: (i) single outbreak, (ii) no transmission, and (iii) a mixture of related and unrelated isolates. Differences of >10 summed tandem repeat differences (STRD) by MLVA and >2 single nucleotide variants (SNVs) by WGS were used to exclude direct transmission.

    Results: 

    Classification of direct transmission by MLVA and WGS was concordant for 1190/1488 (80%) within sCDICC pairs.  For discordant pairs, 229 (15%) had ≥2 SNVs but ≤10 STRD, and 69 (5%) had ≤2 SNVs but ≥10 STRD. Discordant pairs had higher numbers of MLVA variable loci (LV) than concordant pairs, supporting the more diverse measure in each type of discordant pairs; median (IQR) LV between pairs with ≥2 SNVs but ≤10 STRD and ≤2 SNVs but ≥10 STRD were 3 (3-4) and 3 (2-4), respectively, compared with 1 (0-2) between concordant pairs (p=0.001). Conclusion s regarding whether or not sCDICCs comprised real clusters matched for 58/61 (95%) investigations (Table). Discordant conclusions were due to only a single case in each of the 3 remaining investigations.

     

     

    MLVA

     

    Single outbreak

    No transmission

    Mixture

    WGS

    Single outbreak

    33

    0

    1

    No transmission

    0

    10

    1

    Mixture

    1

    0

    15

    Conclusion:

    MLVA and WGS findings were largely concordant, and returned very similar conclusions when applied to outbreak investigations. Tools for MLVA analysis are currently more refined for service use; however future WGS platforms may bring additional benefits, eg. virulence or antimicrobial resistance prediction. Both MLVA and WGS currently offer enhanced discrimination over other genotyping tools.

    Warren Fawley, PhD1, David Eyre, BM BCh2, David Griffiths, BSc3, Derrick Crook, MB BCh4, Tim Peto, DPhil2, A. Sarah Walker, PhD3 and Mark Wilcox, MD5, (1)Leeds Teaching Hospitals & University of Leeds, Leeds, United Kingdom, (2)Nihr Oxford Biomedical Research Centre, Oxford, United Kingdom, (3)National Institute for Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom, (4)Nuffield Department of Medicine, University of Oxford, OXFORD, United Kingdom, (5)Microbiology, Leeds Teaching Hospitals and University of Leeds, Leeds, United Kingdom

    Disclosures:

    W. Fawley, None

    D. Eyre, None

    D. Griffiths, None

    D. Crook, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Consulting fee and Research support

    T. Peto, Optimer Pharmaceuticals: Investigator and Scientific Advisor, Consulting fee and Research support

    A. S. Walker, None

    M. Wilcox, Actelion: Consultant and Research Contractor, Consulting fee and Research support
    Astellas: Consultant and Research Contractor, Consulting fee and Research support
    Biomerieux: Research Contractor, Research support
    Cubist: Consultant and Research Contractor, Consulting fee and Research support
    Pfizer: Consultant, Research Contractor and Speaker's Bureau, Consulting fee, Research support and Speaker honorarium
    Summit: Research Contractor, Research support
    The Medcine Company: Research Contractor, Research support
    Astra Zeneca: Consultant, Consulting fee
    Bayer: Consultant, Consulting fee
    Durata: Consultant, Consulting fee
    J&J: Consultant, Consulting fee
    Merck: Consultant, Consulting fee
    Nabriva: Consultant, Consulting fee
    Novacta: Consultant, Consulting fee
    Novartis: Consultant, Consulting fee
    Optimer: Consultant, Consulting fee
    Sanofi-Pasteur: Consultant, Consulting fee
    The Medicine Company: Consultant, Consulting fee
    VH Squared: Consultant, Consulting fee
    Viropharma: Consultant, Consulting fee

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.