Clinical efficacy and safety of arbekacin for high-risk infections in patients with hematological malignancies

Int J Hematol. 2016 Mar;103(3):334-40. doi: 10.1007/s12185-015-1926-6. Epub 2015 Dec 29.

Abstract

We performed a clinical trial to investigate the efficacy and safety of arbekacin (ABK), a unique aminoglycoside with activity against methicillin-resistant Staphylococcus aureus (MRSA), in patients with hematological malignancies complicated by high-risk infections. ABK was administered intravenously at a dose of approximately 5 mg/kg with various broad-spectrum β-lactams, followed by therapeutic drug monitoring (TDM). A total of 54 febrile or infectious episodes were registered, and TDM was performed in 44 (81%) cases. The absolute neutrophil count was below 500/μl in 49 (91%) cases, and cytotoxic chemotherapy was being administered in 47 (87%) cases. Before initiation of ABK, 52 (96%) patients had received fluoroquinolones (n = 37) and/or broad-spectrum β-lactams (n = 34). There were 10 cases of documented infections including one of MRSA pneumonia, and 44 cases of febrile neutropenia. The efficacy at the end of treatment was 80% for all patients, and efficacy was significantly higher in patients attaining maximum concentrations ≥ 16 µg/ml or receiving TDM-guided dose-adjustment of ABK (n = 19, 95 vs. 71%, P = 0.039). Renal toxicity was observed in six cases (11%) but was generally acceptable. This study demonstrated that TDM-guided ABK administration may be applicable under limited conditions for patients with hematological malignancies.

Keywords: Arbekacin; Coagulase-negative Staphylococci; Febrile neutropenia; Methicillin-resistant Staphylococcus aureus; Therapeutic drug monitoring; Vancomycin.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Infective Agents / administration & dosage*
  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / pharmacokinetics
  • Dibekacin / administration & dosage
  • Dibekacin / adverse effects
  • Dibekacin / analogs & derivatives*
  • Dibekacin / pharmacokinetics
  • Drug Monitoring
  • Drug Therapy, Combination
  • Febrile Neutropenia / drug therapy*
  • Febrile Neutropenia / etiology
  • Female
  • Fluoroquinolones / administration & dosage
  • Hematologic Neoplasms / complications*
  • Humans
  • Infusions, Intravenous
  • Male
  • Methicillin-Resistant Staphylococcus aureus
  • Middle Aged
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / etiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / etiology
  • Treatment Outcome
  • beta-Lactams / administration & dosage

Substances

  • Anti-Infective Agents
  • Fluoroquinolones
  • beta-Lactams
  • Dibekacin
  • arbekacin