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Molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates

  • 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.

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Author:Tilman SchultzeORCiDGND, Philip FerstlORCiDGND, David VillingerGND, Michael HogardtORCiDGND, Wolf Otto BechsteinORCiDGND, Stephan GöttigORCiDGND, Thomas Alexander WichelhausORCiD, Stefan ZeuzemORCiDGND, Jonel TrebickaORCiDGND, Oliver WaidmannORCiDGND, Martin-Walter WelkerGND, Volkhard A. J. KempfORCiDGND
URN:urn:nbn:de:hebis:30:3-620362
DOI:https://doi.org/10.3389/fmicb.2021.791574
ISSN:1664-302X
Parent Title (English):Frontiers in microbiology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Language:English
Date of Publication (online):2021/11/22
Date of first Publication:2021/11/22
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/06/22
Tag:antimicrobial stewardship; carbapenem resistance; infection control; liver transplantation; transmission; whole-genome sequencing
Volume:12,2021
Issue:art. 791574
Page Number:10
First Page:1
Last Page:10
Note:
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.
Note:
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/.
HeBIS-PPN:497506483
Institutes:Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung 4.0