Abstract
ObjectivesRecently, KPC-producing P. aeruginosa has rapidly emerged and expanded in East China. Here we described the clinical impact and characteristics of bloodstream infections (BSIs) from the dominant KPC-producing CRPA belonging to Sequence Type (ST) 463.MethodsRetrospective cohort study was performed with CRPA BSI cases from 2019 to 2020 in a hospital in East China. Clinical characteristics, risk factors, and all-course mortality were evaluated. All CRPA isolates had whole-genome sequencing, antimicrobial susceptibility testing, and serum resistance assay. Representative isolates were tested for virulence in a Galleria mellonella infection model.ResultsAmong the 50 CRPA BSI cases, ST463 predominated (48.0%). In multivariate analysis, we found three independent risk factors for fatal outcome: KPC carriage (OR 4.8; CI95% 1.0-23.7; P = 0.05), Pitt bacteremia score (OR 1.3; CI95% 1.0-1.6; P = 0.02), and underlying hematological disease (OR 8.5; CI95% 1.6-46.4; P = 0.01). The baseline clinical variables were not statistically different across STs, however the 28-day mortality was significantly higher in ST463 cases than that in non-ST463 cases (66.7% vs 33.3%, P = 0.03). ExoU and exoS virulence genes coexisted in all ST463 isolates, and the carbapenem resistant gene bla KPC were produced in almost all ST463 isolates, significantly higher than in the non-ST463 group(95.8% vs 7.7%, P<0.001). ST463 CRPA isolates also showed higher resistance rates to antipseudomonal cephalosporins, monobactam, and fluoroquinolones. And ST463 CRPA was confirmed hypervirulence in the larvae model. The genome of one ST463 CRPA strain showed that the bla KPC-2 gene was the sole resistance gene located on a 41,104bp plasmid pZYPA01, carried on a 7-kb composite transposon-like element flanked by two IS26 elements (IS26–Tn3-tnpA–ISKpn27–bla KPC-2–ISKpn6–IS26). Plasmid from various species presented core bla KPC-2 was franked by mobile genetic element ISKpn27 and ISKpn6. ConclusionsIn the ST463 CRPA BSI cohort, the mortality rates were higher than those in the non-ST463 CRPA BSI. The ST463 CRPA clone coharboring the bla KPC and exoU/exoS genes emerged and spread in East China, which might develop to a new threat in the clinic. Our results suggest that the surveillance of the new high-risk clone, ST463 CRPA, should be strengthened in China, even worldwide in the future.
Highlights
Pseudomonas aeruginosa (PA) is a common and serious cause of nosocomial bloodstream infection; it is often severe when patients have compromised immunity
In a recent report from a hospital in Zhejiang, ST463 carbapenem-resistant Pseudomonas aeruginosa (CRPA) emerged and has become the predominant CRPA clone among the population (Hu et al, 2021a)
There is still a lack of clinical studies on bloodstream infections of the new-onset KPC-producing CRPA belonging to ST463
Summary
Pseudomonas aeruginosa (PA) is a common and serious cause of nosocomial bloodstream infection; it is often severe when patients have compromised immunity. The common resistance mechanisms of P. aeruginosa to carbapenems are the loss of the outer membrane protein OprD and the overexpression of efflux pumps and/or the intrinsic chromosomally encoded AmpC b-lactamase (Li et al, 2012; Potron et al, 2015; Pang et al, 2019). Another mechanism for carbapenem resistance is the production of carbapenemases such as Metallo-b-lactamases. Some studies reported that blaKPC in CRPA might be transmitted from carbapenem-resistant Enterobacteriaceae. Clinical studies of BSIs by the emerging ST463 P. aeruginosa are still lacking
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