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.
Article and author information
Author details
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
- Miles P Davenport, University of New South Wales, Australia
Publication history
- Received: July 25, 2019
- Accepted: November 26, 2019
- Accepted Manuscript published: December 3, 2019 (version 1)
- 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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