Emergence of Carbapenem-Resistant Providencia rettgeri and Providencia stuartii Producing IMP-Type Metallo-β-Lactamase in Japan

Four Providencia rettgeri isolates and one Providencia stuartii isolate were obtained from urine samples of five patients in 2018 in Japan. All of the isolates were resistant to imipenem and meropenem, and three were highly resistant to both carbapenems, with MICs of 512 μg/ml. The three highly carbapenem-resistant isolates harbored bla_IMP-70, encoding a variant of IMP-1 metallo-β-lactamase with two amino acid substitutions (Val67Phe and Phe87Val), and the other two harbored bla_IMP-1 and bla_IMP-11, respectively. Whole-genome sequencing revealed that an isolate harbored two copies of bla_IMP-1 on the chromosome and that the other four harbored a copy of bla_IMP-11 or bla_IMP-70 in a plasmid. Expression of bla_IMP-70 conferred carbapenem resistance in Escherichia coli Recombinant IMP-70 and an IMP-1 variant with Val67Phe but without Phe87Val had significant higher hydrolytic activities against meropenem than recombinant IMP-1, indicating that an amino acid substitution of Val67Phe affects increased activities against meropenem in IMP-70. These results suggest that Providencia spp. become more highly resistant to carbapenems by acquisition of two copies of bla_IMP-1 or by mutation of bla_IMP genes with amino acid substitutions, such as bla_IMP-70.