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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Commonly Used Oncology Drugs Decrease Antifungal Effectiveness against Candida and Aspergillus Species
Arielle Butts1, Parker Reitler2, Wenbo Ge1
1Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.
Abstract:
The incidence of invasive fungal infections has risen significantly in recent decades as medical interventions have become increasingly aggressive. These infections are extremely difficult to treat due to the extremely limited repertoire of systemic antifungals, the development of drug resistance, and the extent to which the patient's immune function is compromised. Even when the appropriate antifungal therapies are administered in a timely fashion, treatment failure is common, even in the absence of in vitro microbial resistance. In this study, we screened a small collection of FDA-approved oncolytic agents for compounds that impact the efficacy of the two most widely used classes of systemic antifungals against Candida albicans, Candida glabrata, and Aspergillus fumigatus We have identified several drugs that enhance fungal growth in the presence of azole antifungals and examine the potential that these drugs directly affect fungal fitness, specifically antifungal susceptibility, and may be contributing to clinical treatment failure.
Insights
Certain cancer drugs may unexpectedly worsen invasive fungal infections by reducing antifungal medication effectiveness. This research highlights a potential cause for treatment failure in patients with conditions like candidiasis and aspergillosis.
Area of Science:
- Medical Mycology
- Pharmacology
- Oncology
Background:
- Invasive fungal infections (IFIs) are increasing due to aggressive medical treatments.
- Limited antifungal options, drug resistance, and compromised immunity complicate IFIs treatment.
- Treatment failure is common, even without microbial resistance.
Purpose of the Study:
- To screen FDA-approved oncolytic agents for effects on antifungal efficacy.
- To identify compounds impacting the effectiveness of azole antifungals.
- To investigate if oncolytic agents contribute to clinical treatment failure.
Main Methods:
- Screening of FDA-approved oncolytic agents.
- Testing against common fungal pathogens: *Candida albicans*, *Candida glabrata*, and *Aspergillus fumigatus*.
- Evaluating impact on antifungal susceptibility in the presence of azole antifungals.
Main Results:
- Several oncolytic agents were identified that enhance fungal growth.
- These drugs reduce the efficacy of azole antifungals against tested fungi.
- Potential direct impact of oncolytic agents on fungal fitness and antifungal susceptibility.
Conclusions:
- Certain FDA-approved oncolytic agents can negatively affect antifungal treatment efficacy.
- These findings suggest a mechanism contributing to clinical treatment failure in IFIs.
- Further investigation into oncolytic agent-fungal interactions is warranted.
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