LUPETTI A, BROUWER CP, WELLING MM, BOGAARDS S, DOGTEROM-BALLERING H, VAN DISSEL JT, NIBBERING PH; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. M-366.
Dept. of Infect. Dis., Leiden University Medical Center, Leiden, Netherlands.
BACKGROUND: In light of the need of new antifungal regimens we investigated whether the human lactoferrin-derived peptide hLF(1-11) is effective against infections with fluconazole-resistant Candida albicans and whether the combination of this peptide with fluconazole acts synergistically against such infections. METHODS: Fluconazole-resistant C. albicans (1=10[5] CFU/ml) were intravenously injected into immunocompromised mice. Twenty-four hours thereafter, mice received i.v. injection with hLF(1-11) followed or not by a subcutaneous injection with fluconazole. The number of surviving yeasts in kidneys at 24 h after treatment was determined microbiologically. RESULTS: Our results indicated that within 24 h after injection of the peptide into mice with a systemic infection with fluconazole-resistant C. albicans the number of viable yeasts decreased with increasing doses of the peptide and maximal effects were seen with 4-40 microg peptide/kg. Moreover, the combination of non-candidacidal concentrations of the peptide and therapeutical concentrations of fluconazole were effective in decreasing the number of viable yeasts in mice with systemic candidadiasis. In additional experiments we found that the dose of fluconazole could be reduced at least 100-fold without affecting the candidacidal activity of the combination treatment. CONCLUSION: The peptide hLF(1-11) as well as suboptimal concentrations of the peptide together with fluconazole were highly effective against systemic infections with fluconazole-resistant C. albicans in mice. Importantly, this peptide rendered fluconazole-resistant C. albicans sensitive to this azole.
Publication Types:
Keywords:
- Animals
- Antifungal Agents
- Antigens, Fungal
- Candida albicans
- Fluconazole
- Humans
- Lactoferrin
- Mice
- Peptides
- immunology
Other ID:
UI: 102264533
From Meeting Abstracts