High Rates of Human Fecal Carriage of mcr-1-Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families

• Published in: Clinical infectious diseases 2018-03, Vol.66 (5), p.676-685
• Main Authors: Zhong, Lan-Lan, Phan, Hang T T, Shen, Cong, Vihta, Karina-Doris, Sheppard, Anna E, Huang, Xi, Zeng, Kun-Jiao, Li, Hong-Yu, Zhang, Xue-Fei, Patil, Sandip, Crook, Derrick W, Walker, A Sarah, Xing, Yong, Lin, Jia-Lin, Feng, Lian-Qiang, Doi, Yohei, Xia, Yong, Stoesser, Nicole, Tian, Guo-Bao
• Format: Article
• Language: English
• Subjects: and Commentaries; Bacteria; Bacterial infections; Cephalosporins; Colistin; Colonization; E coli; Enterobacteriaceae; Gene sequencing; Genetic diversity; Genomes; Insertion; Insertion sequences; Klebsiella; Multidrug resistance; Multidrug resistant organisms; Plasmids; Sampling methods; Strains (organisms); Trends
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cix885

mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1-positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1-positive 3GC-R strains. Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized. Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1-positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1-positive 3GC-R Enterobacteriaceae (P < .001). mcr-1-positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1-positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1-associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs. The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.