Molecular Epidemiology, Natural History, and Long-Term Outcomes of Multidrug-Resistant Enterobacterales Colonization and Infections Among Solid Organ Transplant Recipients
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissionsoup.com..
BACKGROUND: Multidrug-resistant Enterobacterales (MDR-E), including carbapenem-resistant and third-generation cephalosporin-resistant Enterobacterales (CRE, CefR-E), are major pathogens following solid organ transplantation (SOT).
METHODS: We prospectively studied patients who underwent lung, liver, and small bowel transplant from February 2015 through March 2017. Weekly perirectal swabs (up to 100 days post-transplant) were cultured for MDR-E. Whole-genome sequencing (WGS) was performed on gastrointestinal (GI) tract-colonizing and disease-causing isolates.
RESULTS: Twenty-five percent (40 of 162) of patients were MDR-E GI-colonized. Klebsiella pneumoniae was the most common CRE and CefR-E. Klebsiella pneumoniae carbapenemases and CTX-M were leading causes of CR and CefR, respectively. Thirty-five percent of GI colonizers developed MDR-E infection vs 2% of noncolonizers (P < .0001). The attack rate was higher among CRE colonizers than CefR-E colonizers (53% vs 21%, P = .049). GI colonization and high body mass index were independent risk factors for MDR-E infection (P ≤ .004). Thirty-day mortality among infected patients was 6%. However, 44% of survivors developed recurrent infections; 43% of recurrences were late (285 days to 3.9 years after the initial infection). Long-term survival (median, 4.3 years post-transplant) did not differ significantly between MDR-E-infected and MDR-E-noninfected patients (71% vs 77%, P = .56). WGS phylogenetic analyses revealed that infections were caused by GI-colonizing strains and suggested unrecognized transmission of novel clonal group-258 sublineage CR-K. pneumoniae and horizontal transfer of resistance genes.
CONCLUSIONS: MDR-E GI colonization was common following SOT and predisposed patients to infections by colonizing strains. MDR-E infections were associated with low short- and long-term mortality, but recurrences were frequent and often occurred years after initial infections. Findings provide support for MDR-E surveillance in our SOT program.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
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Enthalten in: |
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America - 74(2022), 3 vom: 11. Feb., Seite 395-406 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Hong Nguyen, M [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 14.03.2022 Date Revised 12.05.2022 published: Print Citation Status MEDLINE |
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doi: |
10.1093/cid/ciab427 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM325218552 |
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100 | 1 | |a Hong Nguyen, M |e verfasserin |4 aut | |
245 | 1 | 0 | |a Molecular Epidemiology, Natural History, and Long-Term Outcomes of Multidrug-Resistant Enterobacterales Colonization and Infections Among Solid Organ Transplant Recipients |
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520 | |a © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissionsoup.com. | ||
520 | |a BACKGROUND: Multidrug-resistant Enterobacterales (MDR-E), including carbapenem-resistant and third-generation cephalosporin-resistant Enterobacterales (CRE, CefR-E), are major pathogens following solid organ transplantation (SOT) | ||
520 | |a METHODS: We prospectively studied patients who underwent lung, liver, and small bowel transplant from February 2015 through March 2017. Weekly perirectal swabs (up to 100 days post-transplant) were cultured for MDR-E. Whole-genome sequencing (WGS) was performed on gastrointestinal (GI) tract-colonizing and disease-causing isolates | ||
520 | |a RESULTS: Twenty-five percent (40 of 162) of patients were MDR-E GI-colonized. Klebsiella pneumoniae was the most common CRE and CefR-E. Klebsiella pneumoniae carbapenemases and CTX-M were leading causes of CR and CefR, respectively. Thirty-five percent of GI colonizers developed MDR-E infection vs 2% of noncolonizers (P < .0001). The attack rate was higher among CRE colonizers than CefR-E colonizers (53% vs 21%, P = .049). GI colonization and high body mass index were independent risk factors for MDR-E infection (P ≤ .004). Thirty-day mortality among infected patients was 6%. However, 44% of survivors developed recurrent infections; 43% of recurrences were late (285 days to 3.9 years after the initial infection). Long-term survival (median, 4.3 years post-transplant) did not differ significantly between MDR-E-infected and MDR-E-noninfected patients (71% vs 77%, P = .56). WGS phylogenetic analyses revealed that infections were caused by GI-colonizing strains and suggested unrecognized transmission of novel clonal group-258 sublineage CR-K. pneumoniae and horizontal transfer of resistance genes | ||
520 | |a CONCLUSIONS: MDR-E GI colonization was common following SOT and predisposed patients to infections by colonizing strains. MDR-E infections were associated with low short- and long-term mortality, but recurrences were frequent and often occurred years after initial infections. Findings provide support for MDR-E surveillance in our SOT program | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CRE colonization and infection | |
650 | 4 | |a MDR-E colonization | |
650 | 4 | |a MDR-E infection | |
650 | 4 | |a molecular epidemiology | |
650 | 4 | |a solid organ transplant | |
650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
650 | 7 | |a Carbapenems |2 NLM | |
700 | 1 | |a Shields, Ryan K |e verfasserin |4 aut | |
700 | 1 | |a Chen, Liang |e verfasserin |4 aut | |
700 | 1 | |a William Pasculle, A |e verfasserin |4 aut | |
700 | 1 | |a Hao, Binghua |e verfasserin |4 aut | |
700 | 1 | |a Cheng, Shaoji |e verfasserin |4 aut | |
700 | 1 | |a Sun, Jonathan |e verfasserin |4 aut | |
700 | 1 | |a Kline, Ellen G |e verfasserin |4 aut | |
700 | 1 | |a Kreiswirth, Barry N |e verfasserin |4 aut | |
700 | 1 | |a Clancy, Cornelius J |e verfasserin |4 aut | |
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