JAC Advance Access published online on March 24, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh174
© 2004 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Sackler School of Medicine,
Tel-Aviv University, Tel-Aviv, Israel;
* Corresponding author. E-mail: nosherov{at}post.tau.ac.il.
Received 30 December 2003
; 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
Efficacy of allicin, the reactive molecule of garlic,
in inhibiting Aspergillus spp. in vitro,
and in a murine model of disseminated aspergillosis
2 Department of Biological Chemistry,
Weizmann Institute of Science, Rehovot, Israel
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