The Prevalence Of Clinical Mcr-1-carried Enterobacteriaceae And The Transmission Mechanisms Of Mcr-1 Gene

Polymyxin are used as last-resort therapies to treat infections caused by multidrug-resistant Gram-negative bacteria,especially the carbapenem-resistance Enterobacteriaceae(CRE).And polymyxin have been approved for clinical treatment in China recently.The emergence and prevalence of plasmid mediated colistin resistant gene,mcr-1,makes it possible to transfer polymyxin resistance gene horizontally and spread rapidly,which is tended to lead to the prevalence and outbreak of polymyxin-resistant bacteria.Clarifying the prevalent situation and related risk factors of mcr-1-positive Enterobacteriaceae infection as well as the transmission mechanisms of mcr-1 gene may provide significant values for clinicians to identify polymyxinresistant bacteria infections in time and prevent and control infections effectively.The part one included a total of 2066 Escherichia coli and Klebsiella pneumoniae isolated from bloodstream infections patients,which were collected from twenty-eight hospitals of twenty-two provinces and municipalities during September 2013 to November 2014.Polymerase chain reaction(PCR),antimicrobial susceptibility testings(AST),pulsed-field gel electrophoresis(PFGE),S1-PFGE combined with Southern blot,plasmid sequencing were performed to identify the prevalence of mcr-1 gene and polymyxin resistance rate of Enterobacteriaceae isolated from patients with bloodstream infection in China as well as the transmission mechanisms of mcr-1 gene.The results showed that the prevalence of mcr-1 gene and polymyxin resistance rate ofE.coli and K.pneumoniae isolated from bloodstream infection patients in China were1.0%(21/2066)and 1.3%(26/2066),respectively.Most mcr-1-positive Enterobacteriaceae(18/21)often produced extended-spectrum ?-lactamase(ESBLs)simultaneously and leading to multi-drug resistance.The diversity of MLST and PFGE also showed that these mcr-1-positive Enterobacteriaceae were isolated from sporadic cases.All the mcr-1 genes were located on plasmids,and the main plasmid types are Inc I2 and Inc X4.Infections caused by Enterobacteriaceae carrying mcr-1 gene did not affect the prognosis of patients.The part two collected a total of 29100 E.coli isolated from clinical samples of four hospitals(Beijing,Shenyang,Ningbo and Quzhou)in China over the last decade(2008-2017).PCR,AST,S1-PFGE combined with Southern blot and whole genome sequencing were performed to understand the prevalent situation and trend of mcr-1-positive E coli in recent 10 years,clarify the risk factors of mcr-1-positive E coli infections and its influence on prognosis,as well as the transmission mechanisms of mcr-1 gene.The results showed that the prevalence of mcr-1-positive E coli kept at approximately 1%(300/29100)over the last decade and varied minimally among the four selected hospitals.The overall mcr-1-positive rate over the years increased slightly from 0.42% to 1.39% and this increasing trend was statistically significant.The patients harbored mcr-1-positive E coli had not increased the mortality.Cancer,indwelling CVC tube,and hospitalization in the last 3 months were related to mcr-1-positive E.coli infections dependently.The genetic background of mcr-1-positive E coli was diverse and the plasmids rather than the transposons played important role in the transmission of mcr-1 gene.The plasmids carrying mcr-1 gene could integrated with other plasmids to be hybrid plasmids.Although the prevalence of mcr-1-positive Enterobacteriaceae in infectious patients in China remains low,it shows a slightly increasing trend year by year.The mcr-1 gene is mainly transmitted horizontally by plasmids,which is easily to cause the epidemic of mcr-1-positive Enterobacteriaceae.So it still needs to arouse the attention and vigilance of clinical workers.