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

Author:

Crellen Thomas12ORCID,Turner Paul123ORCID,Pol Sreymom13ORCID,Baker Stephen24ORCID,Nguyen Thi Nguyen To4,Stoesser Nicole2,Day Nicholas PJ12,Turner Claudia123,Cooper Ben S12ORCID

Affiliation:

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

2. Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

3. Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia

4. Oxford University Clinical Research Unit, Centre for Tropical Medicine, Ho Chi Minh City, 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 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.

Funder

Wellcome

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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