Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Oxford University Clinical Research Unit, Centre for Tropical Medicine, Ho Chi Minh City, Viet Nam
To Nguyen Thi Nguyen
Oxford University Clinical Research Unit, Centre for Tropical Medicine, Ho Chi Minh City, Viet Nam
Nicole Stoesser
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Nicholas PJ Day
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Claudia Turner
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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.
