Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance to the point that one or more drugs used to fight them are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance.
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. For certain infections it is given with flucytosine. It is typically given intravenously.
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.
Fusarium is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil microbial community. Some species produce mycotoxins in cereal crops that can affect human and animal health if they enter the food chain. The main toxins produced by these Fusarium species are fumonisins and trichothecenes. Despite most species apparently being harmless, some Fusarium species and subspecific groups are among the most important fungal pathogens of plants and animals.
An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.
Anidulafungin (INN) is a semisynthetic echinocandin used as an antifungal drug. It was previously known as LY303366. It may also have application in treating invasive Aspergillus infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the echinocandins; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall.
Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.
Fusarium solani is a species complex of at least 26 closely related filamentous fungi in the division Ascomycota, family Nectriaceae. It is the anamorph of Nectria haematococca. It is a common soil inhabiting mold. Fusarium solani is implicated in plant diseases as well as in serious human diseases such as fungal keratitis.
Ceftobiprole, sold under the brand name Zevtera among others, is a fifth-generation cephalosporin antibacterial used for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.
In enzymology, a sterol 14-demethylase (EC 1.14.13.70) is an enzyme of the cytochrome P450 (CYP) superfamily. It is any member of the CYP51 family. It catalyzes a chemical reaction such as:
The enzyme cutinase is a member of the hydrolase family. It catalyzes the following reaction:
Isavuconazonium, sold under the brand name Cresemba, is a systemic antifungal medication of the triazole class which is used to treat invasive aspergillosis and mucormycosis. It is used as the sulfate. It is taken by mouth or given via injection into a vein.
Manogepix (E1210) is an pyridine-isoxazole-based broad-spectrum antifungal. Manogepix targets an enzyme involved in the post-translational modification of fungal proteins.
Scedosporiosis is the general name for any mycosis – i.e., fungal infection – caused by a fungus from the genus Scedosporium. Current population-based studies suggest Scedosporium prolificans and Scedosporium apiospermum to be among the most common infecting agents from the genus, although infections caused by other members thereof are not unheard of. The latter is an asexual form (anamorph) of another fungus, Pseudallescheria boydii. The former is a "black yeast", currently not characterized as well, although both of them have been described as saprophytes.
Orotomides are a class of experimental antifungals. They were discovered in 2015 by British scientists at the pharmaceutical company F2G Ltd. while searching for a new drug for Aspergillus infection. The discovery was formally announced at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 55th meeting during 17-21 September 2015 at San Diego, California, and published the next year in the Proceedings of the National Academy of Sciences. It was found to be effective against most important human fungal infections including those with Aspergillus, Lemontospora (Scedosporium) prolificans, Fusarium, Penicillium spp., and Taloromyces. The most promising drug candidate is designated F901318, chemical name 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-{4-[4-(5-fluoro-pyrimidin-2-yl)piperazin-1-yl]-phenyl}-2-oxo-acetamide. F901318 has been named Olorofim.
Aspergillus giganteus is a species of fungus in the genus Aspergillus that grows as a mold. It was first described in 1901 by Wehmer, and is one of six Aspergillus species from the Clavati section of the subgenus Fumigati. Its closest taxonomic relatives are Aspergillus rhizopodus and Aspergillus longivescia.
Karen Joy Shaw is an American microbiologist and discoverer of novel antifungal and antibacterial compounds. She is best known for her work on aminoglycoside resistance in bacteria as well as leading drug discovery research teams. As Senior Vice President of Biology at Trius Therapeutics, Inc. her work was critical to the development of the oxazolidinone antibiotic tedizolid phosphate (Sivextro) as well as the discovery of the TriBE inhibitors, a novel class of DNA gyrase/Topoisomerase IV antibacterial agents that target both Gram-positive and Gram-negative organisms.[2] As Chief Scientific Officer at Amplyx Pharmaceuticals, Shaw was responsible for the preclinical development of the novel antifungal fosmanogepix, a first-in-class broad-spectrum antifungal prodrug that is currently in Phase 2 clinical development for the treatment of invasive fungal infections. She also discovered APX2039, a unique Gwt1 inhibitor that is in preclinical development for the treatment of cryptococcal meningitis.
Ibrexafungerp, sold under the brand name Brexafemme, is an antifungal medication used to treat vulvovaginal candidiasis (VVC). It is taken orally. It is also currently undergoing clinical trials for other indications via an intravenous (IV) formulation. An estimated 75% of women will have at least one episode of VVC and 40 to 45% will have two or more episodes in their lifetime.
