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Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis.

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 fungal-burden 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.
AuthorsTomo Mihara, Hiroshi Kakeya, Koichi Izumikawa, Yoko Obata, Tomoya Nishino, Takahiro Takazono, Kosuke Kosai, Yoshitomo Morinaga, Shintaro Kurihara, Shigeki Nakamura, Yoshifumi Imamura, Taiga Miyazaki, Misuzu Tsukamoto, Yoshihiro Yamamoto, Katsunori Yanagihara, Takayoshi Tashiro, Shigeru Kohno
JournalJournal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 20 Issue 2 Pg. 104-8 (Feb 2014) ISSN: 1437-7780 [Electronic] Netherlands
PMID24462443 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Disease. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Aerosols
  • liposomal amphotericin B
  • Amphotericin B
Topics
  • Administration, Inhalation
  • Aerosols (administration & dosage)
  • Amphotericin B (administration & dosage)
  • Animals
  • Antibiotic Prophylaxis
  • Bronchoalveolar Lavage Fluid (microbiology)
  • Disease Models, Animal
  • Female
  • Lung Diseases, Fungal (drug therapy)
  • Mice
  • Mice, Inbred ICR
  • Mucormycosis (drug therapy)
  • Survival Analysis
  • Treatment Outcome

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