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The Journal of antimicrobial chemotherapy v.72 no.2, 2017년, pp.462 - 466   SCI SCIE
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Monotherapy or combination therapy of isavuconazole and micafungin for treating murine mucormycosis

Gebremariam, Teclegiorgis (Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA ); Wiederhold, Nathan P. (University of Texas Health Sciences at San Antonio, San Antonio, TX, USA ); Alqarihi, Abdullah (Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA ); Uppuluri, Priya (Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA ); Azie, Nkechi (Astellas Pharma, Northbrook, IL, USA ); Edwards Jr, John E. (Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA ); Ibrahim, Ashraf S. (Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles (UCLA) Medical Center, Torrance, CA, USA );
  • 초록  

    Objectives 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 . Methods 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. Results 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. Conclusion 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.


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