First detection of chimeric β-lactamase CTX-M-64-producing Salmonella Typhimurium from a domestic source in Japan

Abstract

Salmonella enterica subsp. enterica serovar Typhimurium has recently emerged worldwide as a producer of extended-spectrum β-lactamase (ESBLs). However, such resistant clinical isolates are still rare in Japan. The common types of ESBLs found are the CTX-M type β-lactamases, including novel ones such as CTX-M-64. CTX-M-64 has a chimeric structure that is a combination of the CTX-M-1 and CTX-M-9 groups. In 2017, S. Typhimurium was isolated from cultures of stool, blood, and urine of an 82-year-old man. Here, we describe the discovery of a clinical isolate of S. Typhimurium in Japan. Antimicrobial susceptibility testing revealed that S. Typhimurium was resistant to third- and fourth-generation cephalosporins, including ceftazidime and monobactam. The MICs of ceftazidime and ceftriaxone were restored by clavulanic acid. Whole-genome sequencing analysis revealed that S. Typhimurium had bla_CTX-M-64 gene on an IncHI2/IncHI2A-type plasmid with an assembly length of 174,477 bp. The genetic structure of the region surrounding the bla_CTX-M-64 gene, ISKpn26-ΔISEcp1-bla_CTX-M-64-orf477, was only shared with the chromosome sequence of S. Typhimurium detected from food-producing chicken in Guangdong, China. Although rare, S. Typhimurium can induce bloodstream infections and produces ESBLs. This is the first report of a CTX-M-64-producing Enterobacterales clinical isolate of domestic origin in Japan.