Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying blaVIM–2 and blaKPC–2 Genes That Spread on Different Genetic Environment in Colombia

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with an increase in the frequency of infections caused by multidrug resistant (MDR) and extensively drug resistant (XDR) strains, limiting the available therapeutic options. The most troublesome resistance is the acquisition and production of carbapenemases such as Verona integron-encoded metallo-β-lactamases (VIM), the most frequent and widespread, and the Klebsiella pneumoniae carbapenemases (KPC), which has continuously spread in the last decade. Its dissemination is linked to their location on mobile genetic elements (MGEs). In Colombia, VIM and KPC have been increasing in its frequency showing major successful dissemination. In this article, we molecularly characterized and analyzed the genetic context of blaVIM and blaKPC in carbapenem-resistant P. aeruginosa (CRPA) isolates from infected and colonized patients in two tertiary-care hospitals, one in Medellín and the other in a municipality close to Medellín, both areas with high carbapenemase endemicity in Colombia (2013–2015). Using whole-genome sequencing (WGS), we identified a remarkable variety of genetic backgrounds in these MDR P. aeruginosa isolates carrying blaKPC–2 and blaVIM–2. There were a diversity of class 1 integron and variations in the gene cassettes associated to blaVIM–2, as well as a possible event of spread of blaKPC–2 mediated by a plasmid that contained part of Tn4401b in one infection case. The dissemination of blaVIM–2 and blaKPC–2 in P. aeruginosa in this area in Colombia has been strongly influenced by successful international clones, carrying these genes and additional determinants of resistance on MGEs, accompanied by gene rearrangement under an antimicrobial selection pressure. These findings emphasize the need to implement control strategies based on rational antibiotic use.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries

“…Of note, seven (9.5%) isolates from Colombia carried simultaneously KPC and VIM carbapenemases. Our group identified P. aeruginosa isolates co-harboring KPC and VIM for the first time in 2012, and according to local surveillance studies, strains co-producing these two carbapenemases and belonging to different STs have continuing spreading throughout the country ( Villegas et al, 2007 ; Vanegas et al, 2014 ; Pacheco et al, 2019 ; Rada et al, 2021 ).…”

“…ESBLs have also been associated with decreased susceptibility to TOL. Indeed, ESBLs such as GES-like, PER-1, BEL-1, BEL-2, and VEB-1, and some OXA enzymes like OXA-2 variants, OXA-10, and OXA-14 can significantly affect the efficacy of TOL ( Vanegas et al, 2014 ; Rada et al, 2021 ). In this study only two isolates, one from Argentina and one from Chile were found to carry PER-1 and PER-3, respectively.…”

Emergence of an Extensive Drug Resistant Pseudomonas aeruginosa Strain of Chicken Origin Carrying bla IMP-45 , tet (X6), and tmexCD3 - toprJ3 on an Inc pRBL16 Plasmid

“… P. aeruginosa strains belonging to ST313 were widely disseminated across different continents ( 25 ). They have been described as intestinal colonizers in healthy individuals but were rarely reported from the poultry farm environment ( 26 ).…”

Challenges and Visions for Infectious Diseases in Colombia during the COVID-19 Peripandemic Transition 2021-2023

“…Even more, after the misuse highly promoted during the COVID-19, an increase in antimicrobial resistance, is not only expected, but already observed in many countries, including Colombia 41,42 . The fight against antimicrobial resistance, promotion of antimicrobial stewardship programs and education, are key in this context [43][44][45][46] .…”