Transmission dynamics and control 1 of multidrug-resistant Klebsiella 2 pneumoniae in neonates in a 3 developing country 4

16 Multidrug-resistant Klebsiella pneumoniae is an increasing cause of infant mortality in developing 17 countries. We aimed to develop a quantitative understanding of the drivers of this epidemic by 18 estimating the e ects of antibiotics on nosocomial transmission risk, comparing competing 19 hypotheses about mechanisms of spread, and quantifying the impact of potential interventions. 20 Using a sequence of dynamic models, we analysed data from a one-year prospective carriage study 21 in a Cambodian neonatal intensive care unit with hyperendemic third-generation 22 cephalosporin-resistant K. pneumoniae. All widely-used antibiotics except imipenem were 23 associated with an increased daily acquisition risk, with an odds ratio for the most common 24 combination (ampicillin + gentamicin) of 1.96 (95% CrI 1.18, 3.36). Models incorporating genomic 25 data found that colonisation pressure was associated with a higher transmission risk, indicated 26 sequence type heterogeneity in transmissibility, and showed that within-ward transmission was 27 insu cient to maintain endemicity. Simulations indicated that increasing the nurse-patient ratio 28 could be an e ective intervention. 29

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