Isolation of a -positive strain in Israel predating the earliest observations from India.

Unlabelled: , the most prevalent carbapenemase among carbapenem-resistant Enterobacteriaceae, is thought to have emerged in India, as its initial detection in 2008 was linked to this country, and subsequent retrospective surveys had so far established the earliest -positive strains to be isolated in India in 2005. Molecular dating and analyses suggest emerged within species decades prior to 2005 on a Tn transposon. Despite early reports of elevated rates of carbapenem-resistant species in Israel starting in the 1990s, limited molecular data are available from this location. We searched for among species isolated in Israel between 2001 and 2006. One strain, Ajun-H1-3, isolated in January 2004, carried within a Tn-like transposon on a 49-kb plasmid, pNDM-Ajun-H1-3, making Ajun-H1-3 the earliest NDM-positive isolate observed to date. The pNDM-Ajun-H1-3 plasmid matched numerous BJ01-like NDM-positive plasmids identified from 2005 onward in species as well as Enterobacterales. These results indicate the need for further retrospective work on global strain archives to shed light on the conditions favoring the emergence as well as subsequent evolution and spread of .

Importance: This study presents the earliest observation of , isolated in a geographical region distant from where it is believed to have originated. In doing so, this study provides novel insights into the emergence and spread of , the most prevalent carbapenemase among carbapenem-resistant Enterobacteriaceae, and its associated mobile genetic elements. It also sheds light on the conditions that foster the evolution of antimicrobial resistance, one of the greatest public health challenges we face.