JAC Advance Access originally published online on March 24, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 832-836
© 2004 The British Society for Antimicrobial Chemotherapy
Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in a murine model of disseminated aspergillosis
1 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 2 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
Received 30 December 2003; returned 24 January 2004; revised 4 February 2004; accepted 8 February 2004
Objectives: The evaluation of allicin, the biologically active compound responsible for the antimicrobial activities of freshly crushed garlic cloves, in inhibiting Aspergillus spp. in vitro and in a murine model of disseminated aspergillosis.
Methods: Pure allicin was prepared by reacting synthetic alliin with a stabilized preparation of the garlic enzyme alliinase. We tested the in vitro efficacy of pure allicin against 31 clinical isolates of Aspergillus spp. using a microdilution broth method and following the NCCLS guidelines (document M-38P). Subsequently, the in vivo efficacy of allicin was tested in immunocompetent mice infected intravenously (iv) with Aspergillus fumigatus conidia. Allicin (5 mg/kg body weight) was administered iv once daily for 5 days post-infection or orally (po) (9 mg/kg body weight) for 5 days pre-infection and 10 days post-infection. No ill effects were observed in allicin-treated uninfected mice.
Results: The in vitro MICs and MFCs of allicin were between 8 and 32 mg/L, indicating that allicin in its pure form may be an effective fungicide in vitro. Time–kill studies indicate that allicin exerts its fungicidal activity within 2–12 h of administration in vitro. Allicin treatment significantly prolonged survival of infected mice (P < 0.01) from mean survival time (MST) = 7.7 days in untreated mice to MST = 21.3 and 13.9 days for allicin iv and po treated mice, respectively. Allicin iv treatment led to a significant (P < 0.001) 10-fold reduction in fungal burden in A. fumigatus infected mice as evaluated by quantitative fungal cultures of kidney tissue samples.
Conclusions: These favourable results, despite the short half-life of this compound in vivo, support further studies of controlled sustained release or more prolonged administration of allicin as a treatment for aspergillosis.
Keywords: antifungal treatment, susceptibility testing, mouse models
* Correspondence address. Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Tel-Aviv, Israel. Tel: +972-3-640-9599; Fax: +972-3-640-9160; E-mail: nosherov{at}post.tau.ac.il
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