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...

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Autores principales:	Tilman G. Schultze, Philip G. Ferstl, David Villinger, Michael Hogardt, Wolf O. Bechstein, Stephan Göttig, Thomas A. Wichelhaus, Stefan Zeuzem, Jonel Trebicka, Oliver Waidmann, Martin-Walter Welker, Volkhard A. J. Kempf
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	carbapenem resistance liver transplantation transmission whole-genome sequencing infection control antimicrobial stewardship Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/be945006810d48bf8c3e145d1c5be855
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spelling	oai:doaj.org-article:be945006810d48bf8c3e145d1c5be8552021-11-22T06:17:05ZMolecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates1664-302X10.3389/fmicb.2021.791574https://doaj.org/article/be945006810d48bf8c3e145d1c5be8552021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.791574/fullhttps://doaj.org/toc/1664-302XBackground: 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.Tilman G. SchultzeTilman G. SchultzeTilman G. SchultzePhilip G. FerstlPhilip G. FerstlDavid VillingerDavid VillingerDavid VillingerMichael HogardtMichael HogardtMichael HogardtWolf O. BechsteinStephan GöttigStephan GöttigStephan GöttigThomas A. WichelhausThomas A. WichelhausThomas A. WichelhausStefan ZeuzemStefan ZeuzemJonel TrebickaJonel TrebickaOliver WaidmannOliver WaidmannMartin-Walter WelkerMartin-Walter WelkerVolkhard A. J. KempfVolkhard A. J. KempfVolkhard A. J. KempfFrontiers Media S.A.articlecarbapenem resistanceliver transplantationtransmissionwhole-genome sequencinginfection controlantimicrobial stewardshipMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	carbapenem resistance liver transplantation transmission whole-genome sequencing infection control antimicrobial stewardship Microbiology QR1-502
spellingShingle	carbapenem resistance liver transplantation transmission whole-genome sequencing infection control antimicrobial stewardship Microbiology QR1-502 Tilman G. Schultze Tilman G. Schultze Tilman G. Schultze Philip G. Ferstl Philip G. Ferstl David Villinger David Villinger David Villinger Michael Hogardt Michael Hogardt Michael Hogardt Wolf O. Bechstein Stephan Göttig Stephan Göttig Stephan Göttig Thomas A. Wichelhaus Thomas A. Wichelhaus Thomas A. Wichelhaus Stefan Zeuzem Stefan Zeuzem Jonel Trebicka Jonel Trebicka Oliver Waidmann Oliver Waidmann Martin-Walter Welker Martin-Walter Welker Volkhard A. J. Kempf Volkhard A. J. Kempf Volkhard A. J. Kempf Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
description	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.
format	article
author	Tilman G. Schultze Tilman G. Schultze Tilman G. Schultze Philip G. Ferstl Philip G. Ferstl David Villinger David Villinger David Villinger Michael Hogardt Michael Hogardt Michael Hogardt Wolf O. Bechstein Stephan Göttig Stephan Göttig Stephan Göttig Thomas A. Wichelhaus Thomas A. Wichelhaus Thomas A. Wichelhaus Stefan Zeuzem Stefan Zeuzem Jonel Trebicka Jonel Trebicka Oliver Waidmann Oliver Waidmann Martin-Walter Welker Martin-Walter Welker Volkhard A. J. Kempf Volkhard A. J. Kempf Volkhard A. J. Kempf
author_facet	Tilman G. Schultze Tilman G. Schultze Tilman G. Schultze Philip G. Ferstl Philip G. Ferstl David Villinger David Villinger David Villinger Michael Hogardt Michael Hogardt Michael Hogardt Wolf O. Bechstein Stephan Göttig Stephan Göttig Stephan Göttig Thomas A. Wichelhaus Thomas A. Wichelhaus Thomas A. Wichelhaus Stefan Zeuzem Stefan Zeuzem Jonel Trebicka Jonel Trebicka Oliver Waidmann Oliver Waidmann Martin-Walter Welker Martin-Walter Welker Volkhard A. J. Kempf Volkhard A. J. Kempf Volkhard A. J. Kempf
author_sort	Tilman G. Schultze
title	Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
title_short	Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
title_full	Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
title_fullStr	Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
title_full_unstemmed	Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates
title_sort	molecular surveillance of carbapenem-resistant gram-negative bacteria in liver transplant candidates
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/be945006810d48bf8c3e145d1c5be855
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Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates

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