Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases

Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated. We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 106 conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day -2 to 5 before and after challenge). Survival was monitored until 12 days after challenge. For fungalburden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed. Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy. Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model.;開始ページ : 104;終了ページ : 108;元資料の権利情報 : © 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.;元資料の権利情報 : NOTICE: this is the author's version of a work that was accepted for publication in Journal of Infection and Chemotherapy. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Infection and Chemotherapy, 20, 2, (2014)



書名 Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis
著作者等 日本化学療法学会
三原 智
書名別名 侵襲性肺ムーコル症マウスに対するアムホテリシンB脂質製剤吸入療法の有用性
出版元 日本化学療法学会・日本感染症学会
刊行年月 c1995-
ページ数 v.
大きさ 28 cm
ISSN 1341321X
NCID AA11057978
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言語 英語
出版国 日本

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