Document Detail


Therapeutic and prophylactic efficacy of aminocandin (IP960) against disseminated candidiasis in mice.
MedLine Citation:
PMID:  18397335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Extended interval dosing of the echinocandins has been suggested as a potential strategy to overcome the need for daily intravenous administration. This study evaluated the therapeutic and prophylactic efficacy of single doses of aminocandin, a new echinocandin in preclinical development, in a murine model of invasive candidiasis. For therapy, groups of mice were infected with Candida albicans, followed by a single dose of aminocandin (1-15 mg/kg) or placebo (mannitol 5% w/v) administered 1 day after inoculation. As prophylaxis, mice were given a single dose (5 or 30 mg/kg) of aminocandin, caspofungin, or placebo at increasing intervals between dose and inoculation. In both treatment and prophylaxis studies, survival was assessed at 21 days post-inoculation. The reduction in fungal burden was assessed in kidney tissue on day 8 post-inoculation. For treatment, single doses of aminocandin of >/=2.5 mg/kg prolonged survival significantly. In addition, the two doses evaluated for reductions in fungal burden (5 and 15 mg/kg) revealed fungicidal activity. As prophylaxis, both aminocandin and caspofungin 5 and 30 mg/kg prolonged survival when given 7 days before inoculation. Aminocandin and caspofungin 30 mg/kg were both able to prolong survival when the interval between dose and inoculation was increased to 10 days. When this interval was extended to 14 days, only aminocandin 30 mg/kg prolonged survival and reduced fungal burden. These results demonstrate that single doses of aminocandin are effective as treatment and prophylaxis, and suggest that extended interval dosing may be a useful strategy for treating invasive candidiasis.
Authors:
L K Najvar; R Bocanegra; N P Wiederhold; C Lambros; N Najarian; T F Patterson; J R Graybill
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-05
Journal Detail:
Title:  Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases     Volume:  14     ISSN:  1469-0691     ISO Abbreviation:  Clin. Microbiol. Infect.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-08     Completed Date:  2008-07-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9516420     Medline TA:  Clin Microbiol Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  595-600     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. najvar@uthscsa.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antifungal Agents / administration & dosage,  therapeutic use*
Candida albicans / drug effects
Candidiasis / drug therapy*,  prevention & control*
Colony Count, Microbial
Disease-Free Survival
Echinocandins / administration & dosage,  therapeutic use
Kidney / microbiology
Lipopeptides
Lipoproteins / administration & dosage,  therapeutic use*
Male
Mice
Mice, Inbred ICR
Grant Support
ID/Acronym/Agency:
N01-AI-25475/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Echinocandins; 0/Lipopeptides; 0/Lipoproteins; 0/aminocandin; 0/caspofungin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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