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Problems of resistant dermatophytes
1Emory University, Atlanta, Ga.
Abstract:
Recalcitrant fungal infections are defined as infections that are difficult or impossible to eradicate despite seemingly adequate treatment with appropriate oral or parenteral antibiotics. Relative or absolute microbial resistance is only one of the many causes of recalcitrance. Others include failure of the patient to comply with the prescribed treatment regimen, drug degradation in the liver, drug-drug interactions, reabsorption or washout of the drug from the stratum corneum, and failure of the drug to reach the stratum corneum. Excretion in the eccrine sweat is the principal pathway by which griseofulvin and ketoconazole, the two currently available oral antifungal agents, are delivered to the stratum corneum. Measures that promote delivery of these drugs to this site by enhancing sweating and minimizing drug run-off and absorption onto clothing may aid in optimizing the therapeutic response to these agents.
Insights
Recalcitrant fungal infections are hard to treat due to various factors beyond just drug resistance. Optimizing antifungal drug delivery to the stratum corneum by enhancing sweating may improve treatment outcomes.
Area of Science:
- Dermatology
- Mycology
- Pharmacology
Background:
- Recalcitrant fungal infections are challenging to eradicate despite appropriate antibiotic treatment.
- Microbial resistance is one cause, but patient compliance, drug metabolism, and drug delivery also contribute.
- Current oral antifungal agents like griseofulvin and ketoconazole rely on eccrine sweat for stratum corneum delivery.
Purpose of the Study:
- To explore the multifaceted causes of recalcitrant fungal infections.
- To identify key factors influencing the efficacy of oral antifungal agents.
- To propose strategies for optimizing antifungal drug delivery to the stratum corneum.
Main Methods:
- Review of existing literature on fungal infections and antifungal pharmacokinetics.
- Analysis of drug delivery pathways to the stratum corneum.
- Identification of factors affecting drug concentration at the site of infection.
Main Results:
- Recalcitrant infections stem from diverse issues including non-compliance, drug degradation, and poor drug penetration.
- Eccrine sweat excretion is the primary route for griseofulvin and ketoconazole to reach the stratum corneum.
- Drug washout and absorption by clothing can reduce efficacy.
Conclusions:
- Optimizing antifungal therapy requires addressing factors beyond microbial resistance.
- Enhancing sweating can improve the delivery of oral antifungals to the stratum corneum.
- Minimizing drug loss through runoff and clothing absorption is crucial for therapeutic success.