Antifungal

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Antifungal
Drug class
Canesten.jpg
Canesten (clotrimazole) antifungal cream
Synonyms antimycotic medication
Legal status
In Wikidata

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. [1]

Contents

Routes of administration

Ocular

Indicated when the fungal infection is located in the eye. There is currently only one ocular antifungal available. This is Natamycin. However, various other antifungal agents could be compounded in this formulation. [2]

Intrathecal

Used occasionally when there's an infection of the central nervous system and other systemic options cannot reach the concentration required in that region for therapeutic benefit. Example(s): amphotericin B. [3]

Vaginal

This may be used to treat some fungal infections of the vaginal region. An example of a condition they are sometimes used for is candida vulvovaginitis which is treated with intravaginal Clotrimazole [4]

Topical

This is sometimes indicated when there's a fungal infection on the skin. An example is tinea pedis; this is sometimes treated with topical terbinafine. [5]

Oral

If the antifungal has good bioavailability, this is a common route to handle a fungal infection. An example is the use of ketoconazole to treat coccidioidomycosis. [6]

Intravenous

Like the oral route, this will reach the bloodstream and distribute throughout the body. However, it is faster and a good option if the drug has poor bioavailability. An example of this is IV amphotericin B for the treatment of coccidioidomycosis. [6]

Classes

The available classes of antifungal drugs are still limited but as of 2021 novel classes of antifungals are being developed and are undergoing various stages of clinical trials to assess performance. [7]

Polyenes

A polyene is a molecule with multiple conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic. The polyene antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature (Tg) of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. (In ordinary circumstances membrane sterols increase the packing of the phospholipid bilayer making the plasma membrane more dense.) As a result, the cell's contents including monovalent ions (K+, Na+, H+, and Cl−) and small organic molecules leak, which is regarded as one of the primary ways a cell dies. [8] Animal cells contain cholesterol instead of ergosterol and so they are much less susceptible. However, at therapeutic doses, some amphotericin B may bind to animal membrane cholesterol, increasing the risk of human toxicity. Amphotericin B is nephrotoxic when given intravenously. As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased. Therefore, further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals.[ citation needed ]

Azoles

Azole antifungals inhibit the conversion of lanosterol to ergosterol by inhibiting lanosterol 14α-demethylase. [9] These compounds have a five-membered ring containing two or three nitrogen atoms. [10] The imidazole antifungals contain a 1,3-diazole (imidazole) ring (two nitrogen atoms), whereas the triazole antifungals have a ring with three nitrogen atoms. [11] [10]

Imidazoles

Triazoles

Thiazoles

Allylamines

Allylamines [12] inhibit squalene epoxidase, another enzyme required for ergosterol synthesis. Examples include butenafine, naftifine, and terbinafine. [13] [14] [15]

Echinocandins

Echinocandins inhibit the creation of glucan in the fungal cell wall by inhibiting 1,3-Beta-glucan synthase:

Echinocandins are administered intravenously, particularly for the treatment of resistant Candida species. [16] [17]

Triterpenoids

Others

Side effects

Incidents of liver injury or failure among modern antifungal medicines are very low to non-existent. However, some can cause allergic reactions in people. [33]

There are also many drug interactions. Patients must read in detail the enclosed data sheet(s) of any medicine. For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein, which (among other functions) excretes toxins and drugs into the intestines. [34] Azole antifungals are also both substrates and inhibitors of the cytochrome P450 family CYP3A4, [34] causing increased concentration when administering, for example, calcium channel blockers, immunosuppressants, chemotherapeutic drugs, benzodiazepines, tricyclic antidepressants, macrolides and SSRIs. [35]

Before oral antifungal therapies are used to treat nail disease, a confirmation of the fungal infection should be made. [36] Approximately half of suspected cases of fungal infection in nails have a non-fungal cause. [36] The side effects of oral treatment are significant and people without an infection should not take these drugs. [36]

Azoles are the group of antifungals which act on the cell membrane of fungi. They inhibit the enzyme 14-alpha-sterol demethylase, a microsomal CYP, which is required for the biosynthesis of ergosterol for the cytoplasmic membrane. This leads to the accumulation of 14-alpha-methylsterols resulting in impairment of function of certain membrane-bound enzymes and disruption of close packing of acyl chains of phospholipids, thus inhibiting growth of the fungi. Some azoles directly increase permeability of the fungal cell membrane. [37]

Resistance

Antifungal resistance is a subset of antimicrobial resistance, that specifically applies to fungi that have become resistant to antifungals. Resistance to antifungals can arise naturally, for example by genetic mutation or through aneuploidy. Extended use of antifungals leads to the development of antifungal resistance through various mechanisms. [1]

Some fungi (e.g. Candida krusei and fluconazole) exhibit intrinsic resistance to certain antifungal drugs or classes, whereas some species develop antifungal resistance to external pressures. Antifungal resistance is a One Health concern, driven by multiple extrinsic factors, including extensive fungicidal use, overuse of clinical antifungals, environmental change and host factors. [1]

Like resistance to antibacterials, antifungal resistance can be driven by antifungal use in agriculture. Currently there is no regulation on the use of similar antifungal classes in agriculture and the clinic. [1] [38] [39]

The emergence of Candida auris as a potential human pathogen that sometimes exhibits multi-class antifungal drug resistance is concerning and has been associated with several outbreaks globally. The WHO has released a priority fungal pathogen list, including pathogens with antifungal resistance. [40]

Related Research Articles

<span class="mw-page-title-main">Candidiasis</span> Fungal infection due to any type of Candida

Candidiasis is a fungal infection due to any species of the genus Candida. When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth and throat. Other symptoms may include soreness and problems swallowing. When it affects the vagina, it may be referred to as a yeast infection or thrush. Signs and symptoms include genital itching, burning, and sometimes a white "cottage cheese-like" discharge from the vagina. Yeast infections of the penis are less common and typically present with an itchy rash. Very rarely, yeast infections may become invasive, spreading to other parts of the body. This may result in fevers, among other symptoms.

<span class="mw-page-title-main">Nystatin</span> Antifungal medication

Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.

<span class="mw-page-title-main">Amphotericin B</span> Antifungal and antiparasitaric chemical compound

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.

<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

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.

<span class="mw-page-title-main">Ergosterol</span> Chemical compound

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.

<span class="mw-page-title-main">Terbinafine</span> Antifungal medication

Terbinafine is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment should not be used for fungal nail infections.

<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc.. It is a member of a class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall.

<span class="mw-page-title-main">Terconazole</span> Chemical compound

Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis.

Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi. These polyene antimycotics are typically obtained from certain species of Streptomyces bacteria. Previously, polyenes were thought to bind to ergosterol in the fungal cell membrane, weakening it and causing leakage of K+ and Na+ ions, which could contribute to fungal cell death. However, more detailed studies of polyene molecular properties have challenged this model suggesting that polyenes instead bind and extract ergosterol directly from the cellular membrane thus disrupting the many cellular functions ergosterols perform. Amphotericin B, nystatin, and natamycin are examples of polyene antimycotics. They are a subgroup of macrolides.

<i>Nakaseomyces glabratus</i> Species of fungus

Nakaseomyces glabratus is a species of haploid yeast of the genus Nakaseomyces, previously known as Candida glabrata. Despite the fact that no sexual life cycle has been documented for this species, N. glabratus strains of both mating types are commonly found. N. glabrata is generally a commensal of human mucosal tissues, but in today's era of wider human immunodeficiency from various causes, N. glabratus is often the second or third most common cause of candidiasis as an opportunistic pathogen. Infections caused by N. glabratus can affect the urogenital tract or even cause systemic infections by entrance of the fungal cells in the bloodstream (Candidemia), especially prevalent in immunocompromised patients.

<span class="mw-page-title-main">Sertaconazole</span> Antifungal medication

Sertaconazole, sold under the brand name Ertaczo among others, is an antifungal medication of the Benzothiophene class. It is available as a cream to treat skin infections such as athlete's foot.

<span class="mw-page-title-main">Butenafine</span> Chemical compound

Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop, is a synthetic benzylamine derived antifungal drug.

<span class="mw-page-title-main">Echinocandin</span> Group of chemical compounds

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 dubbed 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.

<span class="mw-page-title-main">Sterol 14-demethylase</span> Class of enzymes

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:

<span class="mw-page-title-main">Clotrimazole</span> Chemical compound

Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.

Pneumocandin B<sub>0</sub> Chemical compound

Pneumocandin B0, also known as pneumocandin B0, pneumocandin B(0), and hydroxy echinocandin, is an organic chemical compound with the formula C50H80N8O17, produced by the fungus Glarea lozoyensis.

Invasive candidiasis is an infection (candidiasis) that can be caused by various species of Candida yeast. Unlike Candida infections of the mouth and throat or vagina, invasive candidiasis is a serious, progressive, and potentially fatal infection that can affect the blood (fungemia), heart, brain, eyes, bones, and other parts of the body.

<i>Candida tropicalis</i> Species of fungus

Candida tropicalis is a species of yeast in the genus Candida. It is a common pathogen in neutropenic hosts, in whom it may spread through the bloodstream to peripheral organs. For invasive disease, treatments include amphotericin B, echinocandins, or extended-spectrum triazole antifungals.

Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.

References

  1. 1 2 3 4 Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. (29 March 2022). "Tackling the emerging threat of antifungal resistance to human health". Nature Reviews Microbiology. 20 (9): 557–571. doi:10.1038/s41579-022-00720-1. ISSN   1740-1526. PMC   8962932 . PMID   35352028.
  2. ↑ Mcgee K (2019). "Chapter 68 - Ocular pharmacology". Naplex review guide (3rd ed.). United states: McGraw Hill Medical. ISBN   978-1-260-13592-3.
  3. ↑ Nau R, Blei C, Eiffert H (17 June 2020). "Intrathecal Antibacterial and Antifungal Therapies". Clinical Microbiology Reviews. 33 (3): e00190–19. doi:10.1128/CMR.00190-19. ISSN   0893-8512. PMC   7194852 . PMID   32349999.
  4. ↑ Sobel J. "Candida vulvovaginitis: Treatment". UpToDate. Archived from the original on 15 May 2023. Retrieved 21 May 2023.
  5. ↑ Ward H, Parkes N, Smith C, Kluzek S, Pearson R (April 2022). "Consensus for the Treatment of Tinea Pedis: A Systematic Review of Randomised Controlled Trials". Journal of Fungi. 8 (4): 351. doi: 10.3390/jof8040351 . ISSN   2309-608X. PMC   9027577 . PMID   35448582.
  6. 1 2 Carver P. Pharmacotherapy: a pathophysiological approach (11th ed.).
  7. ↑ Hoenigl M, Sprute R, Egger M, Arastehfar A, Cornely OA, Krause R, et al. (9 October 2021). "The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin". Drugs. 81 (15): 1703–1729. doi:10.1007/s40265-021-01611-0. ISSN   0012-6667. PMC   8501344 . PMID   34626339.
  8. ↑ Baginski M, Czub J (June 2009). "Amphotericin B and its new derivatives - mode of action". Current Drug Metabolism. 10 (5): 459–69. doi:10.2174/138920009788898019. PMID   19689243.
  9. ↑ Sheehan DJ, Hitchcock CA, Sibley CM (January 1999). "Current and emerging azole antifungal agents". Clinical Microbiology Reviews. 12 (1): 40–79. doi:10.1128/cmr.12.1.40. PMC   88906 . PMID   9880474.
  10. 1 2 Dixon DM, Walsh TJ (1996), Baron S (ed.), "Antifungal Agents", Medical Microbiology (4th ed.), Galveston (TX): University of Texas Medical Branch at Galveston, ISBN   978-0-9631172-1-2, PMID   21413319, archived from the original on 12 July 2023, retrieved 2 December 2022
  11. ↑ PubChem. "Imidazole". pubchem.ncbi.nlm.nih.gov. Archived from the original on 10 May 2023. Retrieved 2 December 2022.
  12. ↑ Ameen M (March 2010). "Epidemiology of superficial fungal infections". Clinics in Dermatology. 28 (2). Elsevier Inc.: 197–201. doi:10.1016/j.clindermatol.2009.12.005. PMID   20347663.
  13. ↑ "As Fungal Infections Expand, so Does Market | GEN Magazine Articles | GEN". GEN. 15 February 2012. Archived from the original on 6 September 2015. Retrieved 17 October 2015.
  14. ↑ "Research and Markets: Global Antifungal Therapeutics (Polyenes, Azoles, Echinocandins, Allylamines) Market:Trends and Opportunities (2014-2019) | Business Wire". www.businesswire.com. 28 August 2014. Archived from the original on 4 March 2016. Retrieved 17 October 2015.
  15. ↑ "Tinea Cruris". nurse-practitioners-and-physician-assistants.advanceweb.com. Archived from the original on 1 September 2017. Retrieved 17 October 2015.
  16. ↑ "Echinocandins for the treatment of systemic fungal infection | Canadian Antimicrobial Resistance Alliance (CARA)" (PDF). Archived (PDF) from the original on 9 October 2021. Retrieved 9 May 2015.
  17. ↑ Cappelletty D, Eiselstein-McKitrick K (March 2007). "The echinocandins". Pharmacotherapy. 27 (3): 369–88. doi:10.1592/phco.27.3.369. PMID   17316149. S2CID   32016049.
  18. ↑ Polak A (1983). "Antifungal activity in vitro of Ro 14-4767/002, a phenylpropyl-morpholine". Medical Mycology. 21 (3): 205–213. doi:10.1080/00362178385380321. ISSN   1369-3786. PMID   6635894.
  19. ↑ Sutton CL, Taylor ZE, Farone MB, Handy ST (February 2017). "Antifungal activity of substituted aurones". Bioorganic & Medicinal Chemistry Letters. 27 (4): 901–903. doi:10.1016/j.bmcl.2017.01.012. PMID   28094180.
  20. ↑ Wilson G, Block B (2004). Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN   0-7817-3481-9. Archived from the original on 14 January 2023. Retrieved 8 November 2020.
  21. ↑ Long SF. "Anti-Fungals". Southwestern Oklahoma State University. Archived from the original on 17 June 2008.
  22. ↑ Borkow G (August 2014). "Using Copper to Improve the Well-Being of the Skin". Current Chemical Biology. 8 (2): 89–102. doi:10.2174/2212796809666150227223857. PMC   4556990 . PMID   26361585.
  23. ↑ Docampo R, Moreno SN (1990). "The metabolism and mode of action of gentian violet". Drug Metabolism Reviews. 22 (2–3): 161–78. doi:10.3109/03602539009041083. PMID   2272286.
  24. ↑ Leikin JB, Paloucek FP, eds. (10 August 2007). Poisoning and Toxicology Handbook. CRC Press. doi:10.3109/9781420044805. ISBN   9780429195648.
  25. ↑ Vermes A, Guchelaar HJ, Dankert J (August 2000). "Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions". The Journal of Antimicrobial Chemotherapy. 46 (2): 171–9. doi: 10.1093/jac/46.2.171 . PMID   10933638.
  26. ↑ Olson JM, Troxell T (2021). "Griseofulvin". StatPearls. StatPearls Publishing. PMID   30726008 . Retrieved 22 June 2021.
  27. ↑ "Haloprogin". DrugBank. University of Alberta. 6 November 2006. Archived from the original on 1 January 2007. Retrieved 17 February 2007.
  28. ↑ Brilhante RS, Caetano EP, Lima RA, Castelo Branco DS, Serpa R, Oliveira JS, et al. (October 2015). "In vitro antifungal activity of miltefosine and levamisole: their impact on ergosterol biosynthesis and cell permeability of dimorphic fungi". Journal of Applied Microbiology. 119 (4): 962–9. doi: 10.1111/jam.12891 . PMID   26178247. S2CID   206011501.
  29. ↑ Oliver JD, Sibley GE, Beckmann N, Dobb KS, Slater MJ, McEntee L, et al. (November 2016). "F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase". Proceedings of the National Academy of Sciences of the United States of America. 113 (45): 12809–12814. Bibcode:2016PNAS..11312809O. doi: 10.1073/pnas.1608304113 . PMC   5111691 . PMID   27791100.
  30. ↑ Hope WW, McEntee L, Livermore J, Whalley S, Johnson A, Farrington N, et al. (August 2017). "Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease". mBio. 8 (4): e01157-17. doi:10.1128/mBio.01157-17. PMC   5565967 . PMID   28830945.
  31. ↑ "Systemic Therapy". Rook's Textbook of Dermatology . Vol. 4 (8th ed.). 2010. p. 74.48.
  32. ↑ Gendimenico GJ (2007). "Dermatotherapeutic Agents". Ullmann's Encyclopedia of Industrial Chemistry (7th ed.). doi:10.1002/14356007.a08_301.pub2. ISBN   978-3527306732.
  33. ↑ Kyriakidis I, Tragiannidis A, Munchen S, Groll AH (February 2017). "Clinical hepatotoxicity associated with antifungal agents". Expert Opinion on Drug Safety. 16 (2): 149–165. doi:10.1080/14740338.2017.1270264. PMID   27927037. S2CID   43198078.
  34. 1 2 Lewis RE. "Antifungal Drug Interactions". doctorfungus. Archived from the original on 19 June 2010. Retrieved 23 January 2010.
  35. ↑ Research Cf (24 August 2022). "Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers". FDA. Archived from the original on 4 November 2020. Retrieved 17 April 2023.
  36. 1 2 3 American Academy of Dermatology (February 2013). "Five Things Physicians and Patients Should Question". Choosing Wisely: an initiative of the ABIM Foundation . American Academy of Dermatology. Archived from the original on 1 December 2013. Retrieved 5 December 2013., which cites
    • Roberts DT, Taylor WD, Boyle J (March 2003). "Guidelines for treatment of onychomycosis". The British Journal of Dermatology. 148 (3): 402–10. doi:10.1046/j.1365-2133.2003.05242.x. PMID   12653730. S2CID   33750748.
    • Mehregan DR, Gee SL (December 1999). "The cost effectiveness of testing for onychomycosis versus empiric treatment of onychodystrophies with oral antifungal agents". Cutis. 64 (6): 407–10. PMID   10626104.
  37. ↑ Herrick EJ, Patel P, Hashmi MF (2024), "Antifungal Ergosterol Synthesis Inhibitors", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID   31869062 , retrieved 26 August 2024
  38. ↑ Manyi-Loh C, Mamphweli S, Meyer E, Okoh A (30 March 2018). "Antibiotic Use in Agriculture and Its Consequential Resistance in Environmental Sources: Potential Public Health Implications". Molecules. 23 (4): 795. doi: 10.3390/molecules23040795 . ISSN   1420-3049. PMC   6017557 . PMID   29601469.
  39. ↑ Verweij PE, Arendrup MC, Alastruey-Izquierdo A, Gold JA, Lockhart SR, Chiller T, et al. (20 October 2022). "Dual use of antifungals in medicine and agriculture: How do we help prevent resistance developing in human pathogens?". Drug Resistance Updates. 65: 100885. doi: 10.1016/j.drup.2022.100885 . PMC   10693676 . PMID   36283187. S2CID   253052170.
  40. ↑ Organization WH (25 October 2022). WHO fungal priority pathogens list to guide research, development and public health action (PDF). World Health Organization. ISBN   978-92-4-006024-1. Archived from the original on 26 October 2022. Retrieved 27 October 2022.
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