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Whole-Genome Sequencing Reveals Diversity of Carbapenem-Resistant Pseudomonas aeruginosa Collected Through the Emerging Infections Program

Published online by Cambridge University Press:  02 November 2020

Richard Stanton
Affiliation:
Centers for Disease Control and Prevention
Jonathan Daniels
Affiliation:
Centers for Disease Control and Prevention
Erin Breaker
Affiliation:
Centers for Disease Control and Prevention
Davina Campbell
Affiliation:
Centers for Disease Control and Prevention
Joseph Lutgring
Affiliation:
Centers for Disease Control and Prevention
Jesse Jacob
Affiliation:
Emory University
Elisabeth Vaeth
Affiliation:
Maryland Department of Health
Emily Hancock
Affiliation:
University of New Mexico
Ghinwa Dumyati
Affiliation:
University of Rochester
Jacquelyn Mounsey
Affiliation:
Vanderbilt University
Julian Grass
Affiliation:
Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention Sandra Bulens, Centers for Disease Control and Prevention
Maroya Walters
Affiliation:
Centers for Disease Control and Prevention
Alison Halpin
Affiliation:
US Centers for Disease Control and Prevention
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Abstract

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Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.

Funding: None

Disclosures: None

Type
Poster Presentations
Copyright
© 2020 by The Society for Healthcare Epidemiology of America. All rights reserved.