title: Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital.
abstract: Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated:Candida parapsilosis(9 strains),C. glabrata(4 strains),C. guilliermondii(3 strains), and otherCandidaspecies (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causativeCandidaspecies to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of theCandidaspecies that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC (P= 0.016 andP= 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causativeCandidaspecies were susceptible and/or had wild-type susceptibilityin vitroSystemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC.
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan.
authors.forename: Muneyoshi
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan h-araoka@toranomon.gr.jp.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Araoka
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Asano-Mori
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagoe
authors.affiliation: Department of Infectious Diseases and Infection Control, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yuasa
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kaji
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Kageyama
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nishida
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishiwata
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Takagi
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Yamamoto
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wake
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoneyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002175:Candida / Q000145:classification / Q000254:growth & development / Q000472:pathogenicity*; D058387:Candidemia / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D054714:Echinocandins / Q000494:pharmacology; D005260:Female; D019337:Hematologic Neoplasms / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006761:Hospitals; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D007564:Japan; D055666:Lipopeptides / Q000494:pharmacology; D008297:Male; D000077551:Micafungin; D008875:Middle Aged; D009503:Neutropenia / Q000473:pathology; D012307:Risk Factors; D013256:Steroids / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D065819:Voriconazole / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D054714:Echinocandins; D055666:Lipopeptides; D013256:Steroids; C068538:liposomal amphotericin B; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole; D000077551:Micafungin
keywords: allogeneic hematopoietic stem cell transplantation; breakthrough candidemia; candidemia; micafungin; steroids