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Fungi are eukaryotic organisms found in nearly every environment, with only a limited subset contributing to human disease. These pathogenic fungi can cause infections ranging from mild cutaneous conditions to invasive, life-threatening diseases such as cryptococcal meningitis. Antifungal agents serve as a critical therapeutic class for managing these infections. Understanding the pharmacologic characteristics of antifungal medications—including spectrum of activity, mechanism of action, and pharmacokinetics—is essential for effective treatment selection. This activity provides healthcare professionals with essential information on antifungal resistance trends, clinical guidelines for treating superficial and systemic fungal infections, and therapeutic considerations for high-risk populations, including the immunocompromised. Emphasis is placed on strategies for clinical decision-making, monitoring for efficacy and toxicity, and recognizing drug-drug interactions and adverse effect profiles. The role of emerging antifungal therapies and evolving patterns in fungal epidemiology is also discussed. This activity supports improved patient outcomes through informed prescribing and management of antifungal agents. Objectives: Evaluate the mechanism of action of various antifungal antimicrobials. Identify the approved indications and contraindications for antifungal antimicrobials. Assess the adverse events and toxicity associated with antifungal antimicrobial administration. Implement interprofessional team strategies for improving care coordination and communication with antifungal antimicrobials to treat mycotic infections to achieve optimal patient outcomes. Access free multiple choice questions on this topic.

Pragmatic management of mycoses is dependent on the interprofessional healthcare team characterizing the fungal infection as discussed in the introduction, then selecting the most effective antifungal treatment regimen; this requires a strong understanding of public health/epidemiology, medical microbiology/mycology, clinical pharmacology, and healthcare infrastructure which dictates the application of the first 3. There is currently a diverse and effective arsenal of antifungal agents. Still, the alarming global rise in drug-resistant fungi warrants judicious antifungal prescribing by clinicians, the development of combinatorial strategies, the utilization of antifungal adjuvants, and continued antifungal drug discovery and development. Judicious prescribing begins with the healthcare team selecting the proper regimen based on culture and sensitivity data, patient history, and socioeconomic factors. Providers should work closely with pharmacists and, when appropriate, public health officials to provide therapy that appropriately treats infections. Nurses can also assess patient adherence, help administer the drug in the inpatient setting, answer patient questions, and monitor for adverse drug reactions. The ultimate goal is to provide antifungal therapy without unnecessarily creating drug-resistant organisms, limiting adverse events, and reducing drug-drug interactions. Antifungal stewardship is crucial for preserving the effectiveness of current antifungal agents.[51] Combination therapy comprises treatment regimens that incorporate multiple antifungals from different classes and antifungal agents combined with non-antifungal agents. Non-antifungal drug targets include heat shock proteins, calcineurin, lysine acetyltransferase, lysine deacetylase, protein kinase C, and fungal sphingolipids.[52] Antifungal adjuvants can enhance or extend the efficacy of existing antifungal regimens and limit resistance. Some of these encouraging adjuvants could eventually be the standard of care in antifungal-adjuvant combination therapy. The potential adjuvants include drugs with widely variable mechanisms of action, like cyclosporin A, deferasirox, FK506, tamoxifen, and sertraline.[53]

Antifungal adjuvants can enhance or extend the efficacy of existing antifungal regimens and limit resistance. Some of these encouraging adjuvants could eventually be the standard of care in antifungal-adjuvant combination therapy. The potential adjuvants include drugs with widely variable mechanisms of action, like cyclosporin A, deferasirox, FK506, tamoxifen, and sertraline.[53] Antifungal drug discovery has been bolstered by the Orphan Drug Act (1983) and, more recently, the Generating Antibiotic Incentives Now (GAIN) Act (2012). These policies incentivize pharmaceutical companies and researchers to pursue new leads and expand the existing collection of antifungals. The increasing prevalence of drug-resistant fungal diseases presents a significant challenge to the discovery of antifungal drugs. Yet, there are several promising new drugs and class pipelines, theoretical fungal vaccines, and opportunities to generate compounds that inhibit resistance.[54][55][56] The caveat to all of these potentially promising leads in new drugs and drug classes is the time it takes from discovery to dispensing a new medication, estimated to be roughly 12 years.[57] Unfortunately, this cycle leads to the need for ancillary and interim solutions, which include judicious prescribing to limit resistance, combinatorial therapy, and antifungal adjuvant therapies.