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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 intensive care 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.

Original publication

DOI

10.7554/elife.50468

Type

Journal article

Journal

eLife

Publication Date

03/12/2019

Volume

8

Addresses

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Keywords

Humans, Klebsiella pneumoniae, Klebsiella Infections, Cross Infection, Ampicillin, Gentamicins, Anti-Bacterial Agents, Odds Ratio, Risk Factors, Prospective Studies, Disease Outbreaks, Drug Resistance, Multiple, Bacterial, Polymorphism, Single Nucleotide, Models, Theoretical, Developing Countries, Infant, Newborn, Intensive Care Units, Neonatal, Female, Male, Disease Transmission, Infectious