TY - JOUR
T1 - Molecular Epidemiology, Natural History, and Long-Term Outcomes of Multidrug-Resistant Enterobacterales Colonization and Infections Among Solid Organ Transplant Recipients
AU - Nguyen, M. Hong
AU - Shields, Ryan K.
AU - Chen, Liang
AU - William Pasculle, A.
AU - Hao, Binghua
AU - Cheng, Shaoji
AU - Sun, Jonathan
AU - Kline, Ellen G.
AU - Kreiswirth, Barry N.
AU - Clancy, Cornelius J.
N1 - Funding Information:
The CREST study was supported in part by awards from the Antibacterial Resistance Leadership Group (to M. H. N., National Institute of Allergy and Infectious Diseases grant UM1AI104681) and the National Institutes of Health (R21AI128338 to M. H. N. and R01AI090155 to B. N. K.).
Publisher Copyright:
© 2021 The Author(s).
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - CRE colonization and infection
KW - MDR-E colonization
KW - MDR-E infection
KW - molecular epidemiology
KW - solid organ transplant
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U2 - 10.1093/cid/ciab427
DO - 10.1093/cid/ciab427
M3 - Article
C2 - 33970222
AN - SCOPUS:85124578630
SN - 1058-4838
VL - 74
SP - 395
EP - 406
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -