Abstract
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.
Highlights
Transmissible, mcr1-mediated colistin resistance was recently identified in Escherichia coli and Klebsiella pneumoniae isolates from hospitalized humans, animals and raw meat in China[2], with higher rates in animal samples (~19% versus ~1% in humans)
Mcr-1-harboring strains have been identified in humans, animals and raw meat sampled globally (e.g.(3-13)
CTX-M-55 has been found in E. coli in animals in China, and CTX-M-55/55-like variants were seen with mcr-1 in IncI2 plasmids in two different E. coli strains (ST156, ST117) in this study
Summary
Mcr-1-harboring strains have been identified in humans, animals and raw meat sampled globally (e.g.(3-13). These strains have predominantly been E. coli[14] or Salmonella spp.[3, 5], with up to 20% carriage prevalence in swine and poultry[6, 11], and mcr-1-positive isolates from chickens as early as the 1980s in China and 2007 i
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