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Published on: February 14, 2018
Pentamidine is active in vitro against Fusarium species
Michail S Lionakis1, Russell E Lewis, George Samonis
1Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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 micro g/ml for non-F. solani isolates and 4 micro g/ml for F. solani isolates) and the minimum fungicidal concentration at which 50% of the isolates were killed (8 micro g/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.
Insights
Pentamidine (PNT) shows significant antifungal activity against Fusarium species, including fungicidal effects on non-Fusarium solani isolates. This suggests PNT may be a potential treatment for emerging fusariosis infections.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Fusariosis is an emerging opportunistic mycosis with limited treatment options.
- Current antifungals exhibit restricted activity against Fusarium species.
Purpose of the Study:
- To investigate the in vitro antifungal activity of pentamidine (PNT) against clinical isolates of Fusarium species.
- To determine the efficacy of PNT against both Fusarium solani and non-F. solani isolates.
Main Methods:
- In vitro testing using microdilution, disk diffusion, and viability dye staining.
- Evaluation of PNT activity against 10 clinical Fusarium isolates in various media and conditions.
- Microscopic confirmation of fungicidal activity using fluorescent viability dyes.
Main Results:
- Pentamidine demonstrated significant activity against all tested Fusarium isolates.
- Non-F. solani isolates were more susceptible to PNT than F. solani isolates.
- PNT exhibited fungicidal activity against non-F. solani isolates and was more effective against conidial development and in hypoxic conditions.
Conclusions:
- Pentamidine shows promising in vitro activity against Fusarium species, with notable fungicidal effects.
- The observed MICs and MFCs suggest PNT could be effective at concentrations achievable in human tissues.
- Pentamidine may represent a potential therapeutic agent for managing fusariosis, warranting further in vivo investigation.
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