Isolation of mcr-1-Positive Colistin-Resistant Escherichia coli from Humans
Multidrug resistant gram-negative bacterial infections by Pseudomonas aeruginosa and Acinetobacter species are increasing rapidly overseas. Fortunately, the incidence in Japan is not many. Moreover, carbapenem-resistant Enterobacteriaceae infections which are vitally important in human medical treatment are sometimes reported in the news. Considering both active international exchanges of products and humans and characteristics of antimicrobial resistant bacteria, however, no one can predict when an epidemic condition will occur in Japan. Colistin, which is an essential antibiotic for multidrug resistant bacteria, is regarded as a drug of last resort which is tried after existing drugs have failed to produce an adequate effect.
For human medical treatment, the use of colistin is strictly managed and limited. For food animals, on the other hand, below 50 tons a year of colistin is sold as both medicine for treatment and feed additives for growth stimulation. Therefore, it is a concern that colistin-resistant bacteria in food animals could be transmitted to humans through meat. Although colistin has been used for food animals for a half century in Japan, the incidence of antimicrobial resistant bacteria fortunately remains at a low level.
However, the mobilized colistin resistance (mcr-1) gene, which is capable of horizontal transfer between different strains of a bacterial species was first reported in China in 2015, and many reports about isolation of mcr-1 from animals, meat around the world, and humans overseas have followed by that. Therefore, the medical effects are a concern. In Japan, the isolation frequencies of mcr-1-positive E. coli from healthy cattle, swine and broilers were reported to be 0.16%, 0.97% and 0.69%, and the mcr-1-positive rate in E. coli from sick swine was reported to be 13%. Therefore, the detection of mcr-1 from E. coli derived from humans is of high public interest, and recently, 2 cases were reported in Japan.
In the first report, mcr-1 E. coli was isolated from feces of a patient with acute leukemia in 2017. The patient was prescribed with oral polymyxin B, had an international travel history to Taiwan, and had been living closely to livestock. The isolated strain was resistant to multidrugs, and MICs of colistin was 16μg/mL. The author pointed to a possibility of transmission from livestock. Then, in the second report, mcr-1.5 E. coli was isolated from a Japanese infant who had received carbapenem therapy in 2016. This isolated strain possessed blaCTX-M-8 which is an ESBL-encoding gene, MIC for colistin was 2μg/mL. The serotype was O15-H33, and MLST showed ST7278. The mcr-1.5 gene was located on the Incl2 plasmid, which suggested that the mcr-1.5 was closely related with mcr-1 which was detected from E. coli derived from animals in China and Japan.
These reports suggests that mcr-1 may spread in humans through meat from food-producing animals in Japan. The number of the reports is still few and the reality is unknown, therefore, the monitoring of mcr-1 is needed by construction of a monitoring system of antimicrobial resistant bacteria based on One Health.
Tada T, Uechi K, Nakasone I, Shimada K, Nakamatsu M, Kirikae T: Emergence of a colistin-resistant Escherichia coli clinical isolate harboring mcr-1 in Japan, Int J Infect Dis, 63:21-22, 2017. (DOI: http://dx.doi.org/10.1016/j.ijid.2017.07.023)
Ishii Y, Aoki K, Endo S, Kiyota H, Aoyagi T, Kaku M, Bonomo R, Tateda K.: Spread of mcr-1.5 in the community: an emerging threat, Int J Antimicb Agents, Publish online: Nov 7, 2017.( http://www.ijaaonline.com/article/S0924-8579(17)30388-6/pdf)