Molecular epidemiology of carbapenemase-producing Acinetobacter spp. from Israel, 2001-2006: earliest report of blaNDM predating the oldest known blaNDM-positive strains

Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is a WHO priority 1 critical pathogen. Despite early emergence of elevated CRAb rates in Israel, limited molecular data from this location are available. We searched for carbapenemases among 198 clinical Acinetobacter spp. from Israel between 2001 and 2006. Methods Strains from 3 archives underwent whole-genome sequencing (Illumina NovaSeq on all, MinION on a subset) and computational analyses: assembly (Unicycler), annotation (prokka), identification (Kraken, rpoB similarity), search for carbapenemases (ResFinder, BLDB curation). Findings A. baumannii (Ab) represented 179 (90·4%) Acinetobacter spp. Eighty-four Ab (46·9%) carried a carbapenemase: 38 (45·2%) bla OXA-72 ( bla OXA-24-like); 28 (33·3%) bla OXA-23-like (20 bla OXA-23 and 8 bla OXA-225); 18 (21·5%) bla OXA-58 (16 from 2001-2). Carbapenemase rates increased yearly from 2002 (32%) to 2006 (67%). Eight species of non- baumannii Acinetobacter (NbA) accounted for 19 isolates (9·6%). Two of three A. junii contained bla OXA-58, one of which, Ajun-H1-3, isolated in January 2004, also possessed bla NDM-1. The pNDM-Ajun-H1-3 plasmid matched numerous NDM-positive plasmids reported from 2005 onwards in Acinetobacter spp. as well as Enterobacterales . Interpretation We assessed carbapenemase diversity among Acinetobacter spp. in Israel from 2001-2006. Findings in Ab predate observations elsewhere: rapidly rising carbapenemase rates, driven by bla OXA-23-like and bla OXA-24-like genes replacing bla OXA-58. Among NbA, an A. junii isolated in 2004 carried bla NDM-1, making it the earliest NDM-positive isolate reported to date, preceding those from 2005 in India. Further research into bla NDM’s emergence is warranted, in order to shed light on the evolution and spread of this and other antibiotic-resistance genes. Funding Centre de recherche Charles-Le Moyne; Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke; Fonds de recherche du Québec – Santé; New Frontiers in Research Fund Grant NFRFE-2019-00444; CIFAR-Azrieli Global Scholars Program. ### Competing Interest Statement The authors have declared no competing interest.