1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
Download icon

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
Research Article
  • Cited 1
  • Views 1,562
  • Annotations
Cite this article as: eLife 2019;8:e50468 doi: 10.7554/eLife.50468

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.

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).

Reviewing Editor

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

Publication 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.

Metrics

  • 1,562
    Page views
  • 207
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Epidemiology and Global Health
    Arturo Casadevall et al.
    Research Article Updated

    Background:

    The US Food and Drug Administration authorized COVID-19 convalescent plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the USA.

    Methods:

    We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data.

    Results:

    CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = −0.52, p=0.002) between CCP usage per hospital admission and deaths occurring 2 weeks after admission, and this finding was robust to examination of deaths taking place 1, 2, or 3 weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021.

    Conclusions:

    A strong inverse correlation between CCP use and mortality per admission in the USA provides population-level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.

    Funding:

    There was no specific funding for this study. AC was supported in part by RO1 HL059842 and R01 AI1520789; MJJ was supported in part by 5R35HL139854. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority under Contract No. 75A50120C00096.

    1. Epidemiology and Global Health
    William S Hart et al.
    Short Report Updated

    Background:

    Understanding changes in infectiousness during SARS-COV-2 infections is critical to assess the effectiveness of public health measures such as contact tracing.

    Methods:

    Here, we develop a novel mechanistic approach to infer the infectiousness profile of SARS-COV-2-infected individuals using data from known infector–infectee pairs. We compare estimates of key epidemiological quantities generated using our mechanistic method with analogous estimates generated using previous approaches.

    Results:

    The mechanistic method provides an improved fit to data from SARS-CoV-2 infector–infectee pairs compared to commonly used approaches. Our best-fitting model indicates a high proportion of presymptomatic transmissions, with many transmissions occurring shortly before the infector develops symptoms.

    Conclusions:

    High infectiousness immediately prior to symptom onset highlights the importance of continued contact tracing until effective vaccines have been distributed widely, even if contacts from a short time window before symptom onset alone are traced.

    Funding:

    Engineering and Physical Sciences Research Council (EPSRC).