Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis.
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.
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Tomo
T
Mihara
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: kakeya-ngs@umin.ac.jp.
Hiroshi
H
Kakeya
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Nagasaki University Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan.
Koichi
K
Izumikawa
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoko
Y
Obata
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Tomoya
T
Nishino
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takahiro
T
Takazono
Nagasaki University Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan.
Kosuke
K
Kosai
Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
Yoshitomo
Y
Morinaga
Nagasaki University Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan.
Shintaro
S
Kurihara
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Shigeki
S
Nakamura
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoshifumi
Y
Imamura
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Taiga
T
Miyazaki
Nagasaki University Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan.
Misuzu
M
Tsukamoto
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yoshihiro
Y
Yamamoto
Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.
Katsunori
K
Yanagihara
Department of Health Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takayoshi
T
Tashiro
Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Shigeru
S
Kohno
D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D019072:Antibiotic Prophylaxis; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D009091:Mucormycosis / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
D000336:Aerosols; C068538:liposomal amphotericin B; D000666:Amphotericin B
Aerosolized liposomal amphotericin B; Mucormycosis; Prophylaxis; Rhizopus oryzae; Treatment