Optimizing the Treatment of Invasive Candidiasis-A Case for Combination Therapy
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Published on: October 27, 2023
Rachel M Wake1,2, Phoebe E Allebone-Salt1,2, Larissa L H John3
1Institute for Infection and Immunity, St George's University of London, London, UK.
Abstract:
Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance. In addition to its role in mitigating resistance, combination treatment may improve drug penetration, expedite fungal clearance, and allow lower, less toxic doses of individual drugs to be used. A growing body of laboratory-based evidence suggests that antifungal combinations can yield synergistic activity against Candida spp., including against frequently multidrug-resistant Candida auris. It is imperative to test these combinations in clinical trials, incorporating resistance end points as a marker of success.
Insights
Antifungal combination therapy shows promise in combating invasive candidiasis and drug resistance. Clinical trials are crucial to validate these findings and improve patient outcomes against Candida infections.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Invasive candidiasis presents a growing global health challenge with high mortality and limited treatments.
- Antifungal resistance is rapidly increasing, with multidrug-resistant species posing a serious threat.
- Antifungal monotherapy may contribute to the development of drug resistance.
Purpose of the Study:
- To examine the role of antifungal monotherapy in driving resistance.
- To explore the potential of combination therapy in preventing antifungal resistance and improving treatment outcomes.
- To evaluate the synergistic activity of antifungal combinations against Candida species.
Main Methods:
- Review of existing laboratory-based evidence on antifungal combination therapy.
- Analysis of the mechanisms by which combination therapy may mitigate resistance.
- Consideration of clinical trial designs incorporating resistance end points.
Main Results:
- Laboratory evidence suggests antifungal combinations can exhibit synergistic activity against Candida species.
- Combination therapy may prevent stress adaptation and the emergence of drug resistance.
- Potential benefits include improved drug penetration, faster fungal clearance, and reduced toxicity.
Conclusions:
- Antifungal combination therapy is a promising strategy to combat invasive candidiasis and emerging resistance.
- Further clinical trials are imperative to validate the efficacy and safety of these combinations.
- Incorporating resistance end points in trials is crucial for assessing treatment success.
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