title: Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation.
abstract: Clostridium difficile infection (CDI) is frequently diagnosed in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We characterized early-transplant CDI and its associations, and analyzed serially-collected feces to determine intestinal carriage of toxigenic C. difficile. Fecal specimens were collected longitudinally from 94 patients during allo-HSCT hospitalization, from the start of pre-transplant conditioning until up to 35 days after stem cell infusion. Presence of C. difficile 16S rRNA and tcdB genes was determined. Clinical variables and specimen data were analyzed for association with development of CDI. Historical data from an additional 1144 allo-HSCT patients was also used. Fecal specimens from 37 patients (39%) were found to harbor C. difficile. Early-transplant CDI was diagnosed in 16 of 94 (17%) patients undergoing allo-HSCT; cases were generally mild and resembled non-CDI diarrhea associated with transplant conditioning. CDI was associated with preceding colonization with tcdB-positive C. difficile and conditioning regimen intensity. We found no associations between early-transplant CDI and graft-versus-host disease or CDI later in transplant. CDI occurs with high frequency during the early phase of allo-HSCT, where recipients are pre-colonized with toxigenic C. difficile. During this time, CDI incidence peaks during pre-transplant conditioning, and is correlated to intensity of the treatment. In this unique setting, high rates of CDI may be explained by prior colonization and chemotherapy; however, cases were generally mild and resembled non-infectious diarrhea due to conditioning, raising concerns of misdiagnosis. Further study of this unique population with more discriminating CDI diagnostic tests are warranted.
authors.affiliation: Immunology Program, Sloan-Kettering Institute, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Kinnebrew
authors.affiliation: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.affiliation: Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lipuma
authors.affiliation: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Littmann
authors.affiliation: Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Asia
authors.initials: A
authors.lastname: Gobourne
authors.affiliation: Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: No
authors.affiliation: Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Immunology Program, Sloan-Kettering Institute, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Marcel
authors.initials: M
authors.lastname: van den Brink
authors.affiliation: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Immunology Program, Sloan-Kettering Institute, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Taur
mesh_terms: D000328:Adult; D000368:Aged; D016360:Clostridioides difficile / Q000502:physiology*; D003015:Clostridium Infections / Q000209:etiology*; D015331:Cohort Studies; D023381:Endpoint Determination; D005243:Feces / Q000382:microbiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007422:Intestines / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult