TY  - JOUR
A1  - Schultze, Tilman
A1  - Ferstl, Philip
A1  - Villinger, David
A1  - Hogardt, Michael
A1  - Bechstein, Wolf Otto
A1  - Göttig, Stephan
A1  - Wichelhaus, Thomas Alexander
A1  - Zeuzem, Stefan
A1  - Trebicka, Jonel
A1  - Waidmann, Oliver
A1  - Welker, Martin-Walter
A1  - Kempf, Volkhard A. J.
T1  - Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
T2  - Frontiers in microbiology
N2  - Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.

Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.

Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.

Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.
KW  - carbapenem resistance
KW  - liver transplantation
KW  - transmission
KW  - whole-genome sequencing
KW  - infection control
KW  - antimicrobial stewardship
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62036
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620362
SN  - 1664-302X
N1  - This work was supported by the State of Hesse, Germany (“Hessisches Universitäres Kompetenzzentrum für Krankenhaushygiene” and the LOEWE-Center “ACLF-I, project P5”). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
N1  - The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://www.ncbi.nlm.nih.gov/sra/SRP327397/.
VL  - 12,2021
IS  - art. 791574
SP  - 1
EP  - 10
PB  - Frontiers Media
CY  - Lausanne
ER  -