Echinocandin antifungals
Echinocandin antifungals are a class of medications designed to combat fungal infections by inhibiting the biosynthesis of (1,3)beta-glucan, a crucial component of many fungal cell walls. This mechanism allows echinocandins to selectively target fungi without affecting human cells, as mammals do not produce this compound. These drugs are primarily effective against specific fungi, particularly those belonging to the genera Candida and Aspergillus, while being less effective against others such as Cryptococcus and Fusarium. The first echinocandin approved by the FDA was caspofungin in 2001, followed by micafungin in 2005 and anidulafungin in 2006, all administered intravenously.
Echinocandin antifungals are well-tolerated, though they may cause side effects like headache, cough, and digestive issues. Patients at risk for serious fungal infections, including those with cancer or organ transplants, often require these treatments. However, resistance to echinocandins can develop due to mutations in the genes responsible for synthesizing (1,3)beta-glucan. Echinocandins can also be used in combination with other antifungal medications to enhance treatment efficacy. Overall, this class of antifungals plays a vital role in managing invasive fungal infections, particularly in immunocompromised individuals.
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Echinocandin antifungals
Definition
Echinocandin antifungal drugs inhibit the biosynthesis of a key component of many fungal cell walls called (1,3)beta-glucan. Because this compound does not exist in mammals, echinocandin antifungals inhibit the construction of a material that is critical for many fungal cells but does not directly target processes in human cells.
These drugs are active only against those fungi that possess appreciable quantities of (1,3)beta-glucan in their cell walls. Therefore, the antifungal spectrum of echinocandin antifungals is somewhat limited. Members of the fungal genera Candida and Aspergillus are the most susceptible to echinocandins. Pathogenic fungi such as Cryptococcus, Trichosporon, and members of Zygomycotina, however, are unaffected by these drugs. Likewise, echinocandin antifungals show only limited activity against fungi (such as Fusarium, Scedosporium, Coccidioides, Blastomyces, and Histoplasma) that cause systemic infections. Echinocandin antifungals are also effective against pneumonia caused by Pneumocystis jiroveci (formerly known as P. carinii).
The first echinocandin antifungal approved by the US Food and Drug Administration (FDA) was caspofungin (Cancidas) in 2001. In 2005, the FDA approved micafungin (Mycamine) and in 2006 approved anidulafungin (Eraxis). In 2023, the FDA approved rezafungin (Rezzayo). These four drugs are used to treat invasive Candida or Aspergillus infections, Candida infections of mucous membranes, and candidemia, an infection in which yeast colonizes the bloodstream. Micafungin is especially effective against infections with a specific species of Candida called C. glabrata. Rezzayo is prescribed for patients who have not had success with other echinocandin antifungals. Patients using Rezzayo must be carefully monitored because they may have a reaction to the drug, such as chest tightness or trouble breathing.
Echinocandin antifungals must be given intravenously. In general, they are well tolerated, but they do cause some side effects. They all can cause headache, cough, and digestive problems. Additionally, caspofungin can cause chills and fever; micafungin can cause back pain, sleep disruptions, nosebleeds, loss of appetite, fatigue, and a sore mouth; and anidulafungin can cause pain and swelling at the injection site.
Persons at risk for systemic fungal infections, who typically require treatment with echinocandin antifungal drugs, include those who have cancer and those who have had a transplant. Also at risk are persons who are infected with the human immunodeficiency virus (HIV) and those who use steroid drugs, are malnourished, have uncontrolled diabetes mellitus, or have particular blood, bone marrow, or liver disorders. Echinocandin antifungals interact with some of the drugs given to transplant recipients that suppress the immune system. Caspofungin and micafungin, for example, can increase the blood levels of several antirejection drugs and produce toxic side effects.
Resistance can arise to echinocandin antifungals, as (1,3)beta-glucan is synthesized by an enzyme called (1,3)beta-glucan synthase, the active subunit of which is encoded by FKS genes. Specific mutations in FKS1 can lower the sensitivity of (1,3)beta-glucan synthase to echinocandin antifungals, and fungi that harbor such mutations show clinical resistance to these drugs.
Echinocandin antifungals can also work in combination with other antifungal drugs such as triazoles (fluconazole, posaconazole, voriconazole, itraconazole, and ketoconazole), and with polyenes, which are various preparations of amphotericin B, for particular fungal infections.
Bibliography
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