title: Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital.
abstract: Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking.
  
  
  
  The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility.
  
  
  
  Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
  
  
  
  APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare.
authors: Department of Infectious Diseases, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan. muneyoshi-k@toranomon.gr.jp.
authors: Muneyoshi
authors: M
authors: Kimura
authors: Department of Infectious Diseases, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Hideki
authors: H
authors: Araoka
authors: Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, Japan.
authors: Atsushi
authors: A
authors: Yoshida
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Hisashi
authors: H
authors: Yamamoto
authors: Department of Infectious Diseases, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
authors: Masahiro
authors: M
authors: Abe
authors: Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, Japan.
authors: Yuki
authors: Y
authors: Okamoto
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Mitsuhiro
authors: M
authors: Yuasa
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Kaji
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Kosei
authors: K
authors: Kageyama
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Aya
authors: A
authors: Nishida
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Kazuya
authors: K
authors: Ishiwata
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Shinsuke
authors: S
authors: Takagi
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Go
authors: G
authors: Yamamoto
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Asano-Mori
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Naoyuki
authors: N
authors: Uchida
authors: Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, Japan.
authors: Akira
authors: A
authors: Hishinuma
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Koji
authors: K
authors: Izutsu
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Wake
authors: Department of Hematology, Toranomon Hospital, Tokyo, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Shuichi
authors: S
authors: Taniguchi
authors: Department of Infectious Diseases, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.|Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
authors: Akiko
authors: A
authors: Yoneyama
mesh_terms: D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis / Q000379:methods; D016470:Bacteremia / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000453:epidemiology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006761:Hospitals; D006801:Humans; D007564:Japan / Q000453:epidemiology; D064704:Levofloxacin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013290:Streptococcal Infections / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D034363:Viridans Streptococci / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D064704:Levofloxacin
keywords: Allogeneic hematopoietic stem cell transplantation; Ceftazidime; Febrile neutropenia; Levofloxacin breakthrough; Levofloxacin prophylaxis; Viridans streptococcus