Comparative study on the efficacy of amBisome and fungizone in a mouse model of pulmonary aspergillosis

Koji Takemoto, Yutaka Yamamoto, Yutaka Ueda, Yoshihiro Sumita, Koichiro Yoshida, Yoshihito Niki

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objectives: The aim of this study was to evaluate the efficacy and tissue concentration of AmBisome and Fungizone in murine pulmonary aspergillosis, and to investigate the localization of AmBisome at the infection site. Methods: Mice were infected intratracheally with Aspergillus fumigatus. A single dose of each of the antifungals was administered intravenously 4 h after infection. The efficacy of the antifungal treatment was assessed by the pulmonary fungal burden at 20 h post-treatment and the survival time over 1 month. The pulmonary amphotericin B (AMB) concentration was measured until 48 h after administration. The distribution of AmBisome in the lung was evaluated using rhodamine-labelled AmBisome and an anti-AMB antibody. Results: AmBisome at a dose of ≥1 mg/kg significantly prolonged the survival time of infected mice compared with the control group. At the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in terms of increasing survival and reducing the fungal burden. The pulmonary AMB concentration of 10 mg/kg AmBisome was higher than that of 1 mg/kg Fungizone. Tissue distribution analysis showed that AmBisome was localized at the infection site in the lung, and this might explain the potent in vivo efficacy in this infection model. Conclusions: AmBisome is localized at the infection site in the lung and consequently may fully exhibit its in vivo activity. The efficacy of AmBisome is superior to that of Fungizone against pulmonary aspergillosis.

Original languageEnglish
Pages (from-to)724-731
Number of pages8
JournalJournal of Antimicrobial Chemotherapy
Volume57
Issue number4
DOIs
Publication statusPublished - Apr 1 2006
Externally publishedYes

Fingerprint

Pulmonary Aspergillosis
Amphotericin B
Lung
Infection
liposomal amphotericin B
Rhodamines
Aspergillus fumigatus
Maximum Tolerated Dose
Tissue Distribution

Keywords

  • Amphotericin B deoxycholate
  • Aspergillus fumigatus
  • Liposomal amphotericin B
  • Localization

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Comparative study on the efficacy of amBisome and fungizone in a mouse model of pulmonary aspergillosis. / Takemoto, Koji; Yamamoto, Yutaka; Ueda, Yutaka; Sumita, Yoshihiro; Yoshida, Koichiro; Niki, Yoshihito.

In: Journal of Antimicrobial Chemotherapy, Vol. 57, No. 4, 01.04.2006, p. 724-731.

Research output: Contribution to journalArticle

Takemoto, Koji ; Yamamoto, Yutaka ; Ueda, Yutaka ; Sumita, Yoshihiro ; Yoshida, Koichiro ; Niki, Yoshihito. / Comparative study on the efficacy of amBisome and fungizone in a mouse model of pulmonary aspergillosis. In: Journal of Antimicrobial Chemotherapy. 2006 ; Vol. 57, No. 4. pp. 724-731.
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