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

Author:

Hujer Andrea M.12,Higgins Paul G.34,Rudin Susan D.12,Buser Genevieve L.5,Marshall Steven H.2,Xanthopoulou Kyriaki34,Seifert Harald34,Rojas Laura J.26,Domitrovic T. Nicholas12,Cassidy P. Maureen5,Cunningham Margaret C.5,Vega Robert5,Furuno Jon P.7,Pfeiffer Christopher D.89,Beldavs Zintars G.5,Wright Meredith S.10,Jacobs Michael R.11,Adams Mark D.10ORCID,Bonomo Robert A.1261213

Affiliation:

1. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

2. Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA

3. Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany

4. German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany

5. Public Health Division, Oregon Health Authority, Portland, Oregon, USA

6. Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

7. Department of Pharmacy Practice, Oregon State University/Oregon Health and Science University College of Pharmacy, Portland, Oregon, USA

8. Department of Hospital and Specialty Medicine, VA Portland Health Care System, Portland, Oregon, USA

9. Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland, Oregon, USA

10. J. Craig Venter Institute, La Jolla, California, USA

11. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

12. Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

13. Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

Abstract

ABSTRACT Carbapenem antibiotics are among the mainstays for treating infections caused by Acinetobacter baumannii , especially in the Northwest United States, where carbapenem-resistant A. baumannii remains relatively rare. However, between June 2012 and October 2014, an outbreak of carbapenem-resistant A. baumannii 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 bla OXA carbapenemase gene, later identified as bla OXA-237 . Whole-genome sequencing of all isolates revealed a well-supported separate branch within a global A. baumannii 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 bla OXA-237 , flanked on either side by IS Aba1 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 bla OXA-237 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.

Funder

Veterans Affairs Merit Review

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | Centers for Disease Control and Prevention

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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