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Clin Infect Dis. 2019 Oct 4. pii: ciz973. doi: 10.1093/cid/ciz973. [Epub ahead of print]

Long-term Persistence of an Extensively Drug Resistant Subclade of Globally Distributed Pseudomonas aeruginosa Clonal Complex 446 in an Academic Medical Center.

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Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, USA.
Department of Medicine, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, USA.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago USA.
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, USA.
Pharmacometrics Center of Excellence, Chicago College of Pharmacy, Midwestern University, Downers Grove, USA.
Department of Pharmacy, Northwestern Memorial Hospital, Chicago, USA.
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, USA.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, USA.
Servicio de Microbiología y Unidad de Investigación, Hospital Universitari Son Espases, Institut d'Investigació Sanitaria Illes Balears, Palma de Mallorca, Spain.



Antimicrobial resistance (AMR) is a major challenge in the treatment of infections caused by Pseudomonas aeruginosa. Highly drug-resistant infections are disproportionally caused by a small subset of globally distributed P. aeruginosa sequence types (STs), termed "high-risk clones." We noted that clonal complex (CC) 446 (which includes STs 298 and 446) isolates were repeatedly cultured at one medical center and asked whether this lineage might constitute an emerging high-risk clone.


We searched P. aeruginosa genomes from collections available from several institutions and from a public database for the presence of CC446 isolates. We determined antibacterial susceptibility using microbroth dilution and examined genome sequences to characterize the population structure of CC446 and investigate the genetic basis of AMR.


CC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR with 51.9% (28/54) being multi-drug resistant (MDR) and 53.6% of these (15/28) being extensively drug resistant (XDR). Phylogenetic analysis revealed that most MDR/XDR isolates belonged to a subclade of ST298 (designated ST298*) of which 100% (21/21) were MDR and 61.9% (13/21) were XDR. XDR ST298* was identified repeatedly and consistently at a single academic medical center from 2001-2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron.


CC446 isolates are globally distributed with multiple occurrences of high AMR. The subclade ST298* is responsible for a prolonged epidemic (≥16 years) of XDR infections at an academic medical center. These findings indicate that CC446 is an emerging high-risk clone deserving further surveillance.


Pseudomonas aeruginosa ; antimicrobial resistance; high-risk clone; phylogenetics; plasmid


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