First Detection of Chimeric β-Lactamase CTX-M-64-Producing Salmonella Typhimurium from a Domestic Source in Japan

Salmonella enterica subsp. enterica serovar Typhimurium has recently emerged worldwide as a producer of extended-spectrum β-lactamase (ESBL). However, drug-resistant clinical isolates are rare in Japan. The common types of ESBLs found are the CTX-M-type β-lactamases, including novel β-lactamases such as CTX-M-64. CTX-M-64 has a chimeric structure comprising a combination of the CTX-M-1 and CTX-M-9 groups. In 2017, S. Typhimurium was isolated from stool, blood, and urine cultures of an 82-year-old man. Herein, we describe the discovery of a clinical isolate of S. Typhimurium in Japan. Antimicrobial susceptibility testing revealed that the isolate was resistant to third- and fourth-generation cephalosporins, including ceftazidime and monobactam. The minimum inhibitory concentrations of ceftazidime and ceftriaxone were restored by administration of clavulanic acid. Whole-genome sequencing analysis revealed that the isolate harbored the 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 shared only with the chromosome sequence of S. Typhimurium detected in food-producing chickens in Guangdong, China. Although rare, S. Typhimurium can induce bloodstream infections and produce ESBL. To our knowledge, this is the first report of a CTX-M-64-producing Enterobacterales clinical isolate of domestic origin in Japan.