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Antifungal drug resistance to azoles and polyenes
Mar Masiá Canuto1, Félix Gutiérrez Rodero
1Infectious Diseases Unit, Elche University General Hospital, Alicante, Spain.
Abstract:
There is an increased awareness of the morbidity and mortality associated with fungal infections caused by resistant fungi in various groups of patients. Epidemiological studies have identified risk factors associated with antifungal drug resistance. Selection pressure due to the continuous exposure to azoles seems to have an essential role in developing resistance to fluconazole in Candida species. Haematological malignancies, especially acute leukaemia with severe and prolonged neutropenia, seem to be the main risk factors for acquiring deep-seated mycosis caused by resistant filamentous fungi, such us Fusarium species, Scedosporium prolificans, and Aspergillus terreus. The still unacceptably high mortality rate associated with some resistant mycosis indicates that alternatives to existing therapeutic options are needed. Potential measures to overcome antifungal resistance ranges from the development of new drugs with better antifungal activity to improving current therapeutic strategies with the present antifungal agents. Among the new antifungal drugs, inhibitors of beta glucan synthesis and second-generation azole and triazole derivatives have characteristics that render them potentially suitable agents against some resistant fungi. Other strategies including the use of high doses of lipid formulations of amphotericin B, combination therapy, and adjunctive immune therapy with cytokines are under investigation. In addition, antifungal control programmes to prevent extensive and inappropriate use of antifungals may be needed.
Insights
Antifungal drug resistance in fungal infections is a growing concern, particularly in immunocompromised patients. New therapeutic strategies and antifungal control programs are crucial to combat rising morbidity and mortality.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Fungal infections pose significant morbidity and mortality risks, especially in vulnerable patient populations.
- Antifungal drug resistance is an increasing challenge, driven by factors like azole exposure in Candida species.
- Patients with hematological malignancies and prolonged neutropenia are at high risk for invasive mycoses caused by resistant fungi.
Purpose of the Study:
- To highlight the growing problem of antifungal resistance in fungal infections.
- To identify key risk factors associated with the development of antifungal resistance.
- To explore potential therapeutic strategies to overcome antifungal resistance.
Main Methods:
- Review of epidemiological studies on antifungal drug resistance.
- Analysis of risk factors contributing to resistance, including patient groups and drug exposure.
- Evaluation of emerging therapeutic options and control strategies.
Main Results:
- Azole exposure is a key driver of fluconazole resistance in Candida species.
- Hematological malignancies and neutropenia are significant risk factors for invasive infections by resistant filamentous fungi (e.g., Fusarium, Scedosporium, Aspergillus).
- High mortality rates persist for certain resistant mycoses, underscoring the need for novel treatments.
Conclusions:
- Development of new antifungal drugs, such as beta-glucan synthesis inhibitors and novel azole/triazole derivatives, is essential.
- Improving current therapies with lipid formulations of amphotericin B, combination therapy, and immune modulation shows promise.
- Antifungal stewardship programs are necessary to prevent the inappropriate use of antifungals and mitigate resistance.