Nosocomial Outbreak of Extensively Drug-Resistant Acinetobacter baumannii Isolates Containing bla _OXA-237 Carried on a Plasmid

Abstract

Carbapenem antibiotics are among the mainstays for treating infections caused by , especially in the Northwest United States, where carbapenem-resistant remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant occurred in 16 patients from five health care facilities in the state of Oregon. All isolates were defined as extensively drug resistant. Multilocus sequence typing revealed that the isolates belonged to sequence type 2 (international clone 2 [IC2]) and were>95% similar as determined by repetitive-sequence-based PCR analysis. Multiplex PCR revealed the presence of a carbapenemase gene, later identified as Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global phylogeny. Pacific Biosciences (PacBio) SMRT sequencing was also performed on one isolate to gain insight into the genetic location of the carbapenem resistance gene. We discovered that, flanked on either side by IS elements in opposite orientations, was carried on a 15,198-bp plasmid designated pORAB01-3 and was present in all 16 isolates. The plasmid also contained genes encoding a TonB-dependent receptor, septicolysin, a type IV secretory pathway (VirD4 component, TraG/TraD family) ATPase, an integrase, a RepB family plasmid DNA replication initiator protein, an alpha/beta hydrolase, and a BrnT/BrnA type II toxin-antitoxin system. This is the first reported outbreak in the northwestern United States associated with this carbapenemase. Particularly worrisome is that was carried on a plasmid and found in the most prominent worldwide clonal group IC2, potentially giving pORAB01-3 great capacity for future widespread dissemination.

Failure to Communicate: Transmission of Extensively Drug-ResistantblaOXA-237-ContainingAcinetobacter baumannii—Multiple Facilities in Oregon, 2012–2014

“…All isolates had rep-PCR patterns that clustered with >95% similarity, suggesting clonality. 23 Multilocus sequence type analysis revealed all isolates as ST2, which corresponds to international clone 2, the most prevalent carbapenem-resistant A. baumannii lineage found worldwide. 26 Importantly, whole-genome and plasmid sequencing revealed that all isolates except that in patient ORAB19 carried the plasmid-encoded bla OXA-237 , an uncommon OXA carbapenemase related to OXA-235.…”

“…26 Importantly, whole-genome and plasmid sequencing revealed that all isolates except that in patient ORAB19 carried the plasmid-encoded bla OXA-237 , an uncommon OXA carbapenemase related to OXA-235. 27,28 Details are reported by Hujer et al 23 …”

“…Collaboration between public health surveillance systems and research laboratories, as in this investigation, could facilitate characterization of uncommon transmission pathways and new resistance mechanisms suggested by unusual clinical outbreaks. 23,27,33,34 For example, a search for uncharacterized plasmid-encoded carbapenem resistance genes in 10 A. baumannii isolates from Utah, Illinois, California, and Nevada identified 3 novel OXA enzymes (OXA-235, OXA-236, and OXA-237), including an isolate of bla OXA-237 from California. 27 Furthermore, Ou et al 35 used whole-genome sequencing to show that a clone of A. baumannii can persist over time and across healthcare facilities.…”

“…The Louis Stokes Cleveland Department of Veterans Affairs Medical Center provided testing for the following: antimicrobial susceptibility; bla OXA carbapenemase genes; other bla and aminoglycoside resistance genes; molecular typing by repetitive-sequence-based PCR (rep-PCR) and multilocus sequence type (MLST) Pasteur scheme; and whole-genome and plasmid sequencing. 22,23 …”

Investigation of a Carbapenemase-producing Acinetobacter baumannii outbreak using whole genome sequencing versus a standard epidemiologic investigation

“…The bla OXA-235-like subclass, which includes bla OXA-237 , was first recognised from A. baumannii isolates in the United States and Mexico in 2013 [ 34 ] and was implicated in a multi-center outbreak in Oregon between 2012 and 2014 [ 35 ]. This resistance gene was located on a plasmid found in the most prominent A. baumannii clonal group, representing a potential for extensive dissemination [ 36 ].…”