Within patient genetic diversity of blaKPC harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTEKPC platform

Resistance to carbapenems in Klebsiella pneumoniae has been mostly related with the worldwide dissemination of KPC, largely due to the pandemic clones belonging to the complex clonal (CC) 258. To unravel bla KPC post-endemic clinical impact, here we describe clinical characteristics of 68 patients from a high complexity hospital, and the molecular and genetic characteristics of their 139 bla KPC — K. pneumoniae (KPC- Kp ) isolates. Of the 26 patients that presented relapses or reinfections, 16 had changes in the resistance profiles of the isolates recovered from the recurrent episodes. In respect to the genetic diversity of KPC- Kp isolates, PFGE revealed 45 different clonal complexes (CC). MLST for 12 representative clones showed ST258 was present in the most frequent CC (23.0%), however, remaining 11 representative clones belonged to non-CC258 STs (77.0%). Interestingly, 16 patients presented within-patient genetic diversity of KPC- Kp clones. In one of these, three unrelated KPC- Kp clones (ST258, ST504, and ST846) and a bla KPC — K. variicola isolate (ST182) were identified. For this patient, complete genome sequence of one representative isolate of each clone was determined. In K. pneumoniae isolates bla KPC was mobilized by two Tn 3 -like unrelated platforms: Tn 4401b (ST258) and Tn 6454 (ST504 and ST846) , a new NTE KPC- IIe transposon for first time characterized also determined in the K. variicola isolate of this study. Genome analysis showed these transposons were harbored in different unrelated but previously reported plasmids and in the chromosome of a K. pneumoniae (for Tn 4401b ). In conclusion, in the bla KPC post-endemic dissemination in Colombia, different KPC- Kp clones (mostly non-CC258) have emerged due to integration of the single bla KPC gene in new genetic platforms. This work also shows the intra-patient resistant and genetic diversity of KPC- Kp isolates. This circulation dynamic could impact the effectiveness of long-term treatments.