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In vitro interactions between primycin and different statins in their effects against some clinically important fungi
Ildikó Nyilasi1,2, Sándor Kocsubé1,2, Miklós Pesti3
1Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary.
Abstract:
The in vitro antifungal activities of primycin (PN) and various statins against some opportunistic pathogenic fungi were investigated. PN completely inhibited the growth of Candida albicans (MIC 64 microg ml(-1)) and Candida glabrata (MIC 32 microg ml(-1)), and was very effective against Paecilomyces variotii (MIC 2 microg ml(-1)), but had little effect on Aspergillus fumigatus, Aspergillus flavus or Rhizopus oryzae (MICs >64 microg ml(-1)). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin (FLV) and simvastatin (SIM) exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin (LOV) had a slight effect against all fungal isolates tested, whereas pravastatin was completely ineffective. The in vitro interactions between PN and the different statins were investigated using a standard chequerboard titration method. When PN was combined with FLV, LOV or SIM, both synergistic and additive effects were observed. The extent of inhibition was higher when these compounds were applied together, and the concentrations of PN and the given statin needed to block fungal growth completely could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities was investigated.
Insights
Primycin (PN) and certain statins show antifungal activity against opportunistic fungi. Combining primycin with fluvastatin, lovastatin, or simvastatin demonstrated synergistic effects, enhancing fungal growth inhibition.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Opportunistic fungal infections pose significant threats, especially to immunocompromised individuals.
- Existing antifungal therapies face challenges like resistance and toxicity, necessitating novel treatment strategies.
- Primycin (PN) and statins are compounds with potential, yet their combined antifungal efficacy requires thorough investigation.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of primycin (PN) and various statins against opportunistic pathogenic fungi.
- To investigate the in vitro interactions between primycin and different statins to identify potential synergistic or additive effects.
- To determine the impact of these combinations on reducing effective concentrations for fungal growth inhibition.
Main Methods:
- In vitro antifungal activity was assessed using minimum inhibitory concentration (MIC) assays.
- Standard chequerboard titration method was employed to evaluate drug-drug interactions.
- Tested fungal pathogens included Candida albicans, Candida glabrata, Paecilomyces variotii, Aspergillus fumigatus, Aspergillus flavus, and Rhizopus oryzae.
Main Results:
- Primycin (PN) demonstrated potent activity against Candida albicans and Candida glabrata, and moderate activity against Paecilomyces variotii.
- Flustrin (FLV) and simvastatin (SIM) exhibited broad-spectrum antifungal activity, while atorvastatin, rosuvastatin, and lovastatin (LOV) showed limited effects; pravastatin was ineffective.
- Combinations of PN with FLV, LOV, or SIM resulted in synergistic and additive effects, significantly reducing the required concentrations for complete fungal growth inhibition.
Conclusions:
- Primycin (PN) and specific statins (FLV, SIM, LOV) possess in vitro antifungal properties against key opportunistic fungi.
- The combination of primycin with fluvastatin, lovastatin, or simvastatin offers a promising strategy for enhanced antifungal therapy.
- Synergistic interactions suggest potential for reduced drug dosages and improved treatment outcomes in managing fungal infections.
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