Enterobacter hormaechei co-harbouring bla KPC-2, bla VIM-24, and bla NDM-1: the rise of the ‘unholy trinity’

Background Carbapenem-resistant Enterobacterales (CRE) frequently cause serious, life-threatening infections with limited treatment options. The most common mechanism of carbapenem resistance is carbapenemase production. Colombia is considered endemic for KPC, while metallo-β-lactamases such as NDM and VIM are increasingly circulating. An emerging concern is the appearance of strains harbouring more than one carbapenemase. Here, we report a sentinel Enterobacter hormaechei isolate, highly resistant to β-lactams and co-harbouring three carbapenemases. Methods Enterobacter hormaechei was isolated from the wound of a 22-year-old male and molecularly characterized to decipher its resistance profile. Multiplex real-time PCR was used to screen for carbapenemases. Long-read WGS was performed using ONT MinION™, the genome was assembled de novo and resistome and plasmid types were analysed. Conjugation experiments were performed using E. coli J53-AzR as a recipient. Results Multiplex PCR revealed the presence of blaKPC, blaVIM, and blaNDM. Conjugation experiments yielded blaKPC, and blaKPC-blaVIM-blaNDM transconjugants, suggesting two distinct plasmids. WGS confirmed that blaKPC-2 was encoded on a 58 Kb IncN plasmid, while blaVIM-24 and blaNDM-1 were carried by a 370 Kb multi-replicon plasmid (IncR-IncFII-IncC). Conclusions Although the emergence of triple-carbapenemase producers has been reported, it remains rare. However, sentinel isolates as the one described here (KPC-VIM-NDM) are extremely worrisome since dissemination of multiple carbapenemases could occur via conjugative plasmids in addition to horizontal gene transmission via mobile genetic elements. Considering that Colombia has long been considered a KPC-endemic country, the findings described here call for a thorough epidemiological surveillance to assess the real frequency of Enterobacterales carrying multiple carbapenemases.