Affiliation:
1. Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center
2. Medical School of the University of Crete, Heraklion, Greece
3. College of Pharmacy, University of Houston, Houston, Texas
Abstract
ABSTRACT
Fusariosis is an emerging opportunistic mycosis against which currently used antifungals have limited activity. Here, we investigated the in vitro activities of pentamidine (PNT) against 10 clinical isolates of
Fusarium
species (five
Fusarium solani
isolates and five non-
F. solani
isolates) by using the National Committee for Clinical Laboratory Standards microdilution method in three different media (RPMI, RPMI-2, and a yeast nitrogen base medium), disk diffusion testing, and viability dye staining. PNT had significant activities against all 10
Fusarium
isolates. Non-
F. solani
isolates were more susceptible than
F. solani
isolates (
P
< 0.05). Additionally, PNT was fungicidal against all non-
F. solani
isolates, whereas it had fungistatic effects against four of the five
F. solani
isolates. PNT also exhibited greater activity against conidial than against hyphal development of the fungus. This fungicidal activity against non-
F. solani Fusarium
isolates was confirmed microscopically after staining of PNT-treated
Fusarium oxysporum
hyphae with the fluorescent viability dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC). The MICs at which 50% of the isolates were inhibited (2 μg/ml for non-
F. solani
isolates and 4 μg/ml for
F. solani
isolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 μg/ml for non-
F. solani
isolates) were much lower than the PNT tissue concentrations previously reported in humans using conventional daily intravenous PNT dosing. Finally, PNT was more active against
Fusarium
isolates in a hypoxic environment of in vitro growth (
P
< 0.05). This finding may be clinically significant, because
Fusarium
, an angiotropic mold, causes tissue infarcts with resultant low tissue perfusion. Our findings suggest that PNT may have a role in the management of
Fusarium
infections. Future in vivo studies are needed to verify these in vitro findings.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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