Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country

  1. Thomas Crellen  Is a corresponding author
  2. Paul Turner
  3. Sreymom Pol
  4. Stephen Baker
  5. To Nguyen Thi Nguyen
  6. Nicole Stoesser
  7. Nicholas PJ Day
  8. Claudia Turner
  9. Ben S Cooper  Is a corresponding author
  1. Mahidol University, Thailand
  2. University of Oxford, United Kingdom
  3. Oxford University Clinical Research Unit, Viet Nam

Abstract

Multidrug-resistant Klebsiella pneumoniae is an increasing cause of infant mortality in developing countries. We aimed to develop a quantitative understanding of the drivers of this epidemic by estimating the effects of antibiotics on nosocomial transmission risk, comparing competing hypotheses about mechanisms of spread, and quantifying the impact of potential interventions. Using a sequence of dynamic models, we analysed data from a one-year prospective carriage study in a Cambodian neonatal unit with hyperendemic third-generation cephalosporin-resistant K. pneumoniae. All widely-used antibiotics except imipenem were associated with an increased daily acquisition risk, with an odds ratio for the most common combination (ampicillin + gentamicin) of 1.96 (95% CrI 1.18, 3.36). Models incorporating genomic data found that colonisation pressure was associated with a higher transmission risk, indicated sequence type heterogeneity in transmissibility, and showed that within-ward transmission was insufficient to maintain endemicity. Simulations indicated that increasing the nurse-patient ratio could be an effective intervention.

Data availability

Code for reproducing the statisticalmodel fitting and anonymised patient data are available at https://github.com/tc13/transmission-dynamics-klebsiella. The code for the agent based model and parameter values for forward simulations are available at https://github.com/tc13/ward-infection-ABM. Short read sequence data is available from NCBI under accession numbers PRJNA395864 and PR600JEB24970.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Thomas Crellen

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    For correspondence
    thomas.crellen@ndm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2934-1063
  2. Paul Turner

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1013-7815
  3. Sreymom Pol

    Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephen Baker

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1308-5755
  5. To Nguyen Thi Nguyen

    Centre for Tropical Medicine, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  6. Nicole Stoesser

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Nicholas PJ Day

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  8. Claudia Turner

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  9. Ben S Cooper

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    For correspondence
    Ben@tropmedres.ac
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9445-7217

Funding

Wellcome (106698/Z/14/Z)

  • Nicholas PJ Day

Medical Research Council (MR/K006924/1)

  • Ben S Cooper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Miles P Davenport, University of New South Wales, Australia

Ethics

Human subjects: Written consent was obtained from mothers before study enrolment. The study was reviewed and approved by the Angkor Hospital for Children Institutional Review Board (1055/13 AHC) and the University of Oxford Tropical Ethics Committee (1047-13).

Version history

  1. Received: July 25, 2019
  2. Accepted: November 26, 2019
  3. Accepted Manuscript published: December 3, 2019 (version 1)
  4. Version of Record published: January 23, 2020 (version 2)

Copyright

© 2019, Crellen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Thomas Crellen
  2. Paul Turner
  3. Sreymom Pol
  4. Stephen Baker
  5. To Nguyen Thi Nguyen
  6. Nicole Stoesser
  7. Nicholas PJ Day
  8. Claudia Turner
  9. Ben S Cooper
(2019)
Transmission dynamics and control of multidrug-resistant Klebsiella pneumoniae in neonates in a developing country
eLife 8:e50468.
https://doi.org/10.7554/eLife.50468

Share this article

https://doi.org/10.7554/eLife.50468

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