DETECTIVE: Dissemination and resistance mechanisms of carbapenem-resistant Gram-negative bacilli

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Modern genomic technologies and development of genome analysis tools have been successfully applied to improve our understanding of the emergence, spread, short term evolution, and transmission of clinically important MDR bacteria. Genomic analysis has allowed us to determine with fine scale resolution the role played by inter-hospital patient transfer in national and international dissemination of MDR pathogens. It has allowed us to determine the selective forces which drive the evolution of MDR pathogens in the hospital and within patients and the clinical impact this can impose. Genomic analysis has also been used to identify outbreaks, potential sources of outbreaks, and inform successful interventions to bring an end to outbreaks within hospitals. The scale of the MDR problem in Chinese hospitals is reaching alarming levels. The incidence of morbidity and mortality associated with MDR infections in China has grown year-on-year in the 21st century. Most alarming is the rise in the incidence of infections caused by A. baumannii, E. coli and K. pneumoniae which are resistant to carbapenems, that last line of antibiotics available to treat infections with MDR pathogens. The national CHINET network of clinical microbiology laboratories of 34 sentinel hospitals across China (www.chinets.com) report that in 2017, E. coli, K. pneumoniae and A. baumannii were the top three bacterial species recovered from clinical samples. There were 13,337 known cases of carbapenem resistant A. baumannii (69.3% carbapenem resistance prevalence), 6,434 cases of carbapenem resistant K. pneuomoniae (23% carbapenem resistance prevalence), and 845 cases of carbapenem resistant E. coli (2.3% carbapenem resistance prevalence). It is therefore vital that genomic level investigations of these bacteria are implemented in China immediately, to allow the breakthroughs in understanding transmission, spread, and infection control that have been afforded in the Western world.The proposed research to be conducted by the network will be organised around three independent but inter-connected projects:1) Investigate the reservoirs and routes of transmission of carbapenem resistant K. pneumoniae 2) Investigate the community carriage dynamics of carbapenem resistant E. coli leading to the continuous introduction of strains into hospitals and subsequent infections.3) Investigate the reservoirs and routes of transmission of carbapenem resistant Acinetobacter baumannii.