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

• Published in: Clinical infectious diseases 2020-09, Vol.71 (6), p.1524-1531
• Main Authors: Pincus, Nathan B, Bachta, Kelly E R, Ozer, Egon A, Allen, Jonathan P, Pura, Olivia N, Qi, Chao, Rhodes, Nathaniel J, Marty, Francisco M, Pandit, Alisha, Mekalanos, John J, Oliver, Antonio, Hauser, Alan R
• Format: Article
• Language: English
• Subjects: Academic Medical Centers; and Commentaries; Anti-Bacterial Agents - pharmacology; Drug Resistance, Multiple, Bacterial - genetics; Humans; Microbial Sensitivity Tests; Pharmaceutical Preparations; Phylogeny; Pseudomonas aeruginosa - genetics; Pseudomonas Infections - drug therapy; Pseudomonas Infections - epidemiology
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciz973

Abstract Background 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 1 medical center and asked whether this lineage might constitute an emerging high-risk clone. Methods 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. Results CC446 was globally distributed over 5 continents. CC446 isolates demonstrated high rates of AMR, with 51.9% (28/54) being multidrug-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 through 2017. These isolates harbored a large plasmid that carries a novel antibiotic resistance integron. Conclusions 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. We describe a prolonged epidemic of an extensively drug-resistant subclade of Pseudomonas aeruginosa CC446 at an academic center. CC446 (containing ST298) is globally distributed with multiple reports of high antimicrobial resistance and should be considered an emerging high-risk clone.