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Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis


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Title: Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis
Authors: Mihara, Tomo / Kakeya, Hiroshi / Izumikawa, Koichi / Obata, Yoko / Nishino, Tomoya / Takazono, Takahiro / Kosai, Kosuke / Morinaga, Yoshitomo / Kurihara, Shintaro / Nakamura, Shigeki / Imamura, Yoshifumi / Miyazaki, Taiga / Tsukamoto, Misuzu / Yamamoto, Yoshihiro / Yanagihara, Katsunori / Tashiro, Takayoshi / Kohno, Shigeru
Issue Date: Feb-2014
Publisher: 日本化学療法学会・日本感染症学会 / Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
Citation: Journal of Infection and Chemotherapy, 20(2), pp.104-108; 2014
Abstract: 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.
Keywords: Aerosolized liposomal amphotericin B / Mucormycosis / Prophylaxis / Rhizopus oryzae / Treatment
URI: http://hdl.handle.net/10069/34735
ISSN: 1341321X
DOI: 10.1016/j.jiac.2013.09.002
Rights: © 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. / 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)
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34735

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