KPC-producing Klebsiella pneumoniae ST11 spreading in colonized and infected patient from a Transplant Unit

Purpose: The rational use of antimicrobials is essential and can be achieved through antimicrobial stewardship programs. Although several studies identify the clonal relationships of nosocomial carbapenemase KPC-producing Klebsiella pneumoniae (KPC-Kp) strains, none of them, at our knowledge, investigates at the same time clonal status of colonizing KPC-Kp strains. Our aim was to perform a whole-genome sequencing (WGS) of both, colonizing and infecting KPC-Kp strains, to perform genomic analysis, and identification of acquired antimicrobial resistance genes (ARG). Methods & Materials: A 38 years old woman received a deceased donor kidney transplant in 2013 after 11 years of hemodialysis. The patient developed recurrent urinary tract infections (UTI) with high antibiotic exposition. First sample analyzed was a colonizing strain isolated the first day of hospitalization (HAp39) from a surveillance rectal swab. The second strain was isolated 7 days after hospitalization (HA40) from a urine sample taken in context of UTI suspicion. Both strains showed reduced susceptibility to β-lactams, sulfamethoxazole, trimethoprim, chloramphenicol, tetracycline, and ciprofloxacin according to CLSI, 2020. WGS was carried out using Illumina MiSeq-I, and de novo assembly was performed using SPAdes v.3.11. Genomic analysis was made. Results: Both strains belonged to ST11. They possessed in common a total of 21 transferable ARG, aadA1, aac(6′)-Ib, aph(3′')-Ib, aph(6)-Id, arr-3, blaKPC-2, blaOXA-1, blaOXA-9, blaTEM-1A, catB3, floR, fosA, mph(E), msr(E), oqxA, oqxB, qacEΔ1, qnrB19, sul1, sul2, and tet(A). HAp39 strain also harbored a second carbapenemase blaOXA-163, and a dfrA22-like gene. blaOXA-163 had as flanking sequences IS4(TnpA)-blaOXA-163- HP-Tn3 family (TnpA). Loss of blaOXA-163, and dfrA22-like gene was observed in HA40 strain, though acquisition of blaCTX-M-2, rmtD and a cat-like genes were identified in this strain. The blaKPC-2 gene was located in the same genetic platform (ISKpn27-blaKPC2- ISKpn6-HP-Tn3 (TnpR)) in both strains Conclusion: Colonizing and infecting KPC-Kp strains showed to belong to the same ST11 with a high similarity at DNA level, suggesting they are the same strains. Loss and acquisition of ARG during the hospitalization was observed. Also, a change in epidemiology is being observed displacing KPC-Kp ST258 isolates suggesting that molecular surveillance of ST11 KPC-Kp should be performed in our region to prevent further spread.