Abstract | OBJECTIVES: We analysed the in vitro and in vivo effects of posaconazole and amphotericin B against three clinical isolates of zygomycetes: Lichtheimia corymbifera, F1; and Rhizopus oryzae, F5 and F6. METHODS: In vitro activities of both drugs were assessed by determining MICs, minimum fungicidal concentrations (MFCs) and fungal damage measured by the XTT assay against either the spores or the hyphal forms. Additionally, the survival curves of neutropenic mice systemically infected with the zygomycete isolates were used as the marker of antifungal response to amphotericin B (1 mg/kg/day) or posaconazole (2.5, 10 and 50 mg/kg/day). RESULTS: In terms of MICs, posaconazole proved to be active against the three isolates (MICs ranging from 0.125 to 1.0 mg/L). The median posaconazole MFCs were 0.25, 0.5 and >16 mg/L for F1, F5 and F6, respectively. The XTT assay showed that posaconazole was active against spores of all three isolates, but only partially effective against the hyphae. The survival studies showed that amphotericin B at 1 mg/kg/day and posaconazole at 10 mg/kg/day prolonged the survival of the animals infected with L. corymbifera F1. In mice infected with R. oryzae F5, only posaconazole at 50 mg/kg/day significantly prolonged survival, whereas amphotericin B at 1 mg/kg/day was the only regimen active against R. oryzae F6. CONCLUSIONS: Our findings showed that posaconazole could be useful in the treatment of zygomycosis. Also, we report that an isolate of R. oryzae with low MFC responded to posaconazole, while another isolate with high MFC did not.
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Authors | Elisabetta Spreghini, Fiorenza Orlando, Daniele Giannini, Francesco Barchiesi |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 65
Issue 10
Pg. 2158-63
(Oct 2010)
ISSN: 1460-2091 [Electronic] England |
PMID | 20667887
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antifungal Agents
- Tetrazolium Salts
- Triazoles
- 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide
- posaconazole
- Amphotericin B
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Topics |
- Amphotericin B
(pharmacology, therapeutic use)
- Animals
- Antifungal Agents
(pharmacology, therapeutic use)
- Child
- Disease Models, Animal
- Humans
- Male
- Mice
- Microbial Sensitivity Tests
- Microbial Viability
(drug effects)
- Mucorales
(drug effects, isolation & purification, metabolism)
- Rhizopus
(drug effects, isolation & purification, metabolism)
- Survival Analysis
- Tetrazolium Salts
(metabolism)
- Treatment Outcome
- Triazoles
(pharmacology, therapeutic use)
- Zygomycosis
(drug therapy, microbiology)
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