title: Monotherapy or combination therapy of isavuconazole and micafungin for treating murine mucormycosis.
abstract: Previously we demonstrated the benefit of isavuconazole in treating murine mucormycosis due to Rhizopus. We wanted to determine the efficacy of isavuconazole in treating murine mucormycosis caused by Mucor, the second most common cause of the disease. Furthermore, because we previously determined that Rhizopus possesses the target enzyme for echinocandins and micafungin has activity against murine mucormycosis, we compared the activity of combination therapy (isavuconazole + micafungin) with placebo, either drug alone or standard therapy of liposomal amphotericin B (LAmB) in treating pulmonary murine mucormycosis caused by Rhizopus delemar.
  
  
  
  In vitro susceptibility to isavuconazole of Mucorales was evaluated using the CLSI M38-A2 method. Immunosuppressed mice were intratracheally infected with either Mucor circinelloides or R. delemar. Treatment with isavuconazole (orally), micafungin (intraperitoneally), a combination of both or LAmB (intravenously) was compared, with survival and tissue fungal burden serving as primary and secondary endpoints, respectively.
  
  
  
  Isavuconazole was as effective as LAmB in prolonging survival of mice infected with M. circinelloides. Against R. delemar-induced mucormycosis, all monotherapy treatments significantly improved survival of mice versus placebo without showing superiority over one another. However, LAmB was superior in lowering fungal burden in target organs. Although combination therapy of isavuconazole + micafungin did not enhance survival of mice over monotherapy, antagonism was not detected between the two drugs.
  
  
  
  Isavuconazole is effective in treating pulmonary murine mucormycosis due to Mucor. In addition, combination therapy of isavuconazole + micafungin does not demonstrate synergy and it is not antagonistic against Rhizopus-induced mucormycosis.
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.
authors: Teclegiorgis
authors: T
authors: Gebremariam
authors: University of Texas Health Sciences at San Antonio, San Antonio, TX, USA.
authors: Nathan P
authors: NP
authors: Wiederhold
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.
authors: Abdullah
authors: A
authors: Alqarihi
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.|David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Priya
authors: P
authors: Uppuluri
authors: Astellas Pharma, Northbrook, IL, USA.
authors: Nkechi
authors: N
authors: Azie
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA.|David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: John E
authors: JE
authors: Edwards
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA ibrahim@labiomed.org.|David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors: Ashraf S
authors: AS
authors: Ibrahim
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000627:therapeutic use*; D055666:Lipopeptides / Q000627:therapeutic use*; D008168:Lung / Q000382:microbiology; D008297:Male; D000077551:Micafungin; D051379:Mice; D008826:Microbial Sensitivity Tests; D009089:Mucor / Q000187:drug effects*; D009091:Mucormycosis / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012233:Rhizopus / Q000187:drug effects*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D009570:Nitriles; D011725:Pyridines; D014230:Triazoles; C508735:isavuconazole; D000077551:Micafungin