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Updated: Jul 29, 2025
Quantifying the Antifungal Activity of Peptides Against Candida albicans
Published on: January 13, 2023
Antifungals: From Pharmacokinetics to Clinical Practice
Anália Carmo1, Marilia Rocha2, Patricia Pereirinha2
1Advanced Unit for Pharmacokinetics and Personalized Therapeutics, Clinical Pathology Department, Centro Hospitalar e Universitário de Coimbra, 3004-561 Coimbra, Portugal.
Abstract:
The use of antifungal drugs started in the 1950s with polyenes nystatin, natamycin and amphotericin B-deoxycholate (AmB). Until the present day, AmB has been considered to be a hallmark in the treatment of invasive systemic fungal infections. Nevertheless, the success and the use of AmB were associated with severe adverse effects which stimulated the development of new antifungal drugs such as azoles, pyrimidine antimetabolite, mitotic inhibitors, allylamines and echinochandins. However, all of these drugs presented one or more limitations associated with adverse reactions, administration route and more recently the development of resistance. To worsen this scenario, there has been an increase in fungal infections, especially in invasive systemic fungal infections that are particularly difficult to diagnose and treat. In 2022, the World Health Organization (WHO) published the first fungal priority pathogens list, alerting people to the increased incidence of invasive systemic fungal infections and to the associated risk of mortality/morbidity. The report also emphasized the need to rationally use existing drugs and develop new drugs. In this review, we performed an overview of the history of antifungals and their classification, mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) characteristics and clinical applications. In parallel, we also addressed the contribution of fungi biology and genetics to the development of resistance to antifungal drugs. Considering that drug effectiveness also depends on the mammalian host, we provide an overview on the roles of therapeutic drug monitoring and pharmacogenomics as means to improve the outcome, prevent/reduce antifungal toxicity and prevent the emergence of antifungal resistance. Finally, we present the new antifungals and their main characteristics.
Insights
Antifungal drugs, crucial for invasive fungal infections, face challenges like resistance and toxicity. This review details antifungal history, mechanisms, and new developments, emphasizing personalized medicine to improve outcomes.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Antifungal drug development began in the 1950s, with amphotericin B (AmB) as a key treatment for invasive fungal infections.
- Despite AmB's efficacy, severe side effects spurred the creation of azoles, echinocandins, and other drug classes, each with limitations like toxicity and emerging resistance.
- Rising incidence of invasive fungal infections, highlighted by the WHO's 2022 priority pathogens list, necessitates improved diagnostics, rational drug use, and novel therapeutic strategies.
Purpose of the Study:
- To provide a comprehensive historical overview and classification of antifungal drugs.
- To analyze the mechanisms of action, pharmacokinetics/pharmacodynamics (PK/PD), and clinical applications of existing and emerging antifungals.
- To explore the role of fungal biology, genetics, therapeutic drug monitoring, and pharmacogenomics in combating antifungal resistance and optimizing treatment outcomes.
Main Methods:
- Literature review and synthesis of historical data on antifungal drug development.
- Analysis of scientific literature on antifungal mechanisms, PK/PD, and clinical trial data.
- Examination of research on fungal resistance mechanisms and host-related factors influencing treatment efficacy.
Main Results:
- Detailed classification and historical progression of antifungal agents from polyenes to newer classes.
- Explanation of diverse mechanisms of action and PK/PD profiles influencing drug selection and dosing.
- Identification of key factors in antifungal resistance, including fungal genetics and host-specific responses.
- Highlighting the potential of therapeutic drug monitoring and pharmacogenomics for personalized antifungal therapy.
Conclusions:
- The evolution of antifungals reflects a continuous effort to balance efficacy with safety and overcome resistance.
- Understanding fungal biology and host factors is critical for developing effective strategies against invasive fungal infections.
- Personalized approaches, including therapeutic drug monitoring and pharmacogenomics, offer promising avenues to improve patient outcomes and mitigate antifungal resistance.
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