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Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales

Author

Listed:
  • Kalisvar Marimuthu

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital
    Yong Loo Lin School of Medicine, National University of Singapore and National University Health System)

  • Indumathi Venkatachalam

    (Singapore General Hospital)

  • Vanessa Koh

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital)

  • Stephan Harbarth

    (Infection Control Program, WHO Collaborating Center, Geneva University Hospitals and Faculty of Medicine)

  • Eli Perencevich

    (University of Iowa Carver College of Medicine
    Center for Comprehensive Access & Delivery Research and Evaluation, Iowa City Veterans Affairs Medical Center)

  • Benjamin Pei Zhi Cherng

    (Yong Loo Lin School of Medicine, National University of Singapore and National University Health System
    Singapore General Hospital
    DUKE-NUS Medical School, National University of Singapore)

  • Raymond Kok Choon Fong

    (Changi General Hospital)

  • Surinder Kaur Pada

    (Ng Teng Fong General Hospital)

  • Say Tat Ooi

    (Khoo Teck Puat Hospital)

  • Nares Smitasin

    (Yong Loo Lin School of Medicine, National University of Singapore and National University Health System
    National University Hospital and National University Health System)

  • Koh Cheng Thoon

    (KK Women’s and Children’s Hospital)

  • Paul Anantharajah Tambyah

    (National University Hospital and National University Health System)

  • Li Yang Hsu

    (Yong Loo Lin School of Medicine, National University of Singapore and National University Health System
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    National University of Singapore)

  • Tse Hsien Koh

    (Singapore General Hospital
    DUKE-NUS Medical School, National University of Singapore)

  • Partha Pratim De

    (Tan Tock Seng Hospital)

  • Thean Yen Tan

    (Changi General Hospital)

  • Douglas Chan

    (Ng Teng Fong General Hospital)

  • Rama Narayana Deepak

    (Khoo Teck Puat Hospital)

  • Nancy Wen Sim Tee

    (National University Hospital and National University Health System)

  • Andrea Kwa

    (Singapore General Hospital
    Academic Clinical Programme (Medicine), SingHealth Duke-NUS
    Program in Emerging Infectious Diseases, Duke-NUS Medical School)

  • Yiying Cai

    (Singapore General Hospital
    National University of Singapore)

  • Yik-Ying Teo

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    National University of Singapore)

  • Natascha May Thevasagayam

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital)

  • Sai Rama Sridatta Prakki

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital)

  • Weizhen Xu

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital)

  • Wei Xin Khong

    (Tan Tock Seng Hospital)

  • David Henderson

    (Clinical Centre, National Institutes of Health)

  • Nicole Stoesser

    (Nuffield Department of Medicine, University of Oxford)

  • David W. Eyre

    (Nuffield Department of Population Health, University of Oxford)

  • Derrick Crook

    (Nuffield Department of Medicine, University of Oxford)

  • Michelle Ang

    (National Centre for Infectious Diseases)

  • Raymond Tzer Pin Lin

    (National Centre for Infectious Diseases
    National University Hospital and National University Health System)

  • Angela Chow

    (Tan Tock Seng Hospital
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System
    Lee Kong Chian School of Medicine, Nanyang Technological University)

  • Alex R. Cook

    (Saw Swee Hock School of Public Health, National University of Singapore and National University Health System)

  • Jeanette Teo

    (National University Hospital and National University Health System)

  • Oon Tek Ng

    (National Centre for Infectious Diseases
    Tan Tock Seng Hospital
    Lee Kong Chian School of Medicine, Nanyang Technological University)

Abstract

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients’ admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.

Suggested Citation

  • Kalisvar Marimuthu & Indumathi Venkatachalam & Vanessa Koh & Stephan Harbarth & Eli Perencevich & Benjamin Pei Zhi Cherng & Raymond Kok Choon Fong & Surinder Kaur Pada & Say Tat Ooi & Nares Smitasin &, 2022. "Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30637-5
    DOI: 10.1038/s41467-022-30637-5
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    References listed on IDEAS

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    1. Simon N. Wood, 2011. "Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 73(1), pages 3-36, January.
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