JCHOR
Journal of Current Hematology & Oncology Research

The Journal of Current Hematology & Oncology Research regularly publishes internationally qualified research in hematology and oncology within the current scholarly knowledge. This journal is indexed by indices that are considered international scientific journal indices (DRJI, ESJI, OAJI, etc.). According to the current Associate Professorship criteria, it is within the scope of International Article 1-d. Each article published in this journal corresponds to 5 points.

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Antifungal drugs
Abstract
Fungal infections continue to emerge as an important cause of infectious disease and mortality in humans. Amphotericin B deoxycholate (ABD), was the first antifungal that was discovered, and it was released in 1958, and flucytosine, which was developed later and is effective against Candida and Cryptococcus, was introduced in 1978. The discovery of first-generation azoles (fluconazole and itraconazole) in the 1990s has created a new step in the treatment of fungi. In the years that followed, with the development of lipid formulations of amphotericin B, the introduction of second-generation azoles, and the release of the most recently developed class, echinocandins, the foundations of today’s existing antifungal classes were laid. This article is aimed to review the mechanism of action, side effects and clinical use indications of the main antifungal drugs used in the treatment of systemic fungal infections.

Keywords : Antifungal, mycology, fungal infection

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1. Nett JE, Andes DR. Antifungal Agents: Spectrum of Activity,Pharmacology, and Clinical Indications. Infect Dis Clin North Am.2016;30(1):51-83. doi:10.1016/j.idc.2015.10.012
2. Mani Chandrika KVS, Sharma S. Promising antifungal agents: Aminireview. Bioorg Med Chem. 2020;28(7):115398. doi:10.1016/j.bmc.2020.115398
3. Öncel S, Keçeli SA. Flukonazol. J Fungus. Nisan 2018;9(1):67-75
4. Odds F.C., Antifungal agents: their diversity and increasingsophistication. Mycologist. May 2003;17:51-55. doi: 10.1017/S0269-915X(03)00206-4
5. Robbins N, Cowen LE. Antifungal discovery. Curr Opin Microbiol.2022;69:102198. doi:10.1016/j.mib.2022.102198
6. Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years ofclinical experience. Rev Infect Dis. 1990;12(2):308-329. doi:10.1093/clinids/12.2.308
7. Stevens DA. Antifungal Agents: Amphotericin B. In: Mandell, Douglas,and Bennett’s Principles and Practice of Infectious Diseases.Ed: JohnE. Bennett, Raphael Dolin, Martin J. Blaiser, Ninth Edition, Elsevier,Philadelphia, 2020, p: 497-500.
8. Arikan S, Rex JH. Lipid-based antifungal agents: current status. CurrPharm Des. 2001;7(5):393-415. doi:10.2174/1381612013398031
9. Sabatelli F, Patel R, Mann PA, et al. In vitro activities of posaconazole,fluconazole, itraconazole, voriconazole, and amphotericin B against alarge collection of clinically important molds and yeasts. AntimicrobAgents Chemother. 2006;50(6):2009-2015. doi:10.1128/AAC.00163-06
10. Andes D, Safdar N, Marchillo K, Conklin R. Pharmacokinetic-pharmacodynamic comparison of amphotericin B (AMB) and twolipid-associated AMB preparations, liposomal AMB and AMB lipidcomplex, in murine candidiasis models. Antimicrob Agents Chemother.2006;50(2):674-684. doi:10.1128/AAC.50.2.674-684.2006
11. Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, WalshTJ. Pharmacokinetics, excretion, and mass balance of liposomalamphotericin B (AmBisome) and amphotericin B deoxycholatein humans. Antimicrob Agents Chemother. 2002;46(3):828-833.doi:10.1128/AAC.46.3.828-833.2002
12. Chapman SW, Dismukes WE, Proia LA, et al. Clinical practiceguidelines for the management of blastomycosis: 2008 updateby the Infectious Diseases Society of America. Clin Infect Dis.2008;46(12):1801-1812. doi:10.1086/588300
13. Nocua-Báez LC, Uribe-Jerez P, Tarazona-Guaranga L, Robles R, CortésJA. Azoles de antes y ahora: una revisión [Azoles of then and now: areview]. Rev Chilena Infectol. 2020;37(3):219-230. doi:10.4067/s0716-10182020000300219
14. Pfaller MA, Messer SA, Hollis RJ, Jones RN. In vitro activities ofposaconazole (Sch 56592) compared with those of itraconazoleand fluconazole against 3,685 clinical isolates of Candida spp.and Cryptococcus neoformans. Antimicrob Agents Chemother.2001;45(10):2862-2864. doi:10.1128/AAC.45.10.2862-2864.2001
15. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities ofcaspofungin, itraconazole, posaconazole, ravuconazole, voriconazole,and amphotericin B against 448 recent clinical isolates of filamentousfungi. J Clin Microbiol. 2003;41(8):3623-3626. doi:10.1128/JCM.41.8.3623-3626.2003
16. Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities ofCandida bloodstream isolates to the new triazole antifungal agentsBMS-207147, Sch 56592, and voriconazole. Antimicrob AgentsChemother. 1998;42(12):3242-3244. doi:10.1128/AAC.42.12.3242
17. González GM, Fothergill AW, Sutton DA, Rinaldi MG, Loebenberg D.In vitro activities of new and established triazoles against opportunisticfilamentous and dimorphic fungi. Med Mycol. 2005;43(3):281-284.doi:10.1080/13693780500088416
18. Pettit NN, Carver PL. Isavuconazole: A New Option for theManagement of Invasive Fungal Infections. Ann Pharmacother.2015;49(7):825-842. doi:10.1177/1060028015581679
19. Perlin DS, Shor E, Zhao Y. Update on Antifungal Drug Resistance. CurrClin Microbiol Rep. 2015;2(2):84-95. doi:10.1007/s40588-015-0015-1
20. Thompson III GR. Antifungal Drugs: Azoles. In: Mandell, Douglas,and Bennett’s Principles and Practice of Infectious Diseases. Ed: JohnE. Bennett, Raphael Dolin, Martin J. Blaiser, Ninth Edition, Elsevier,Philadelphia, 2020, p: 501-508
21. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O.Voriconazole therapeutic drug monitoring in patients with invasivemycoses improves efficacy and safety outcomes. Clin Infect Dis.2008;46(2):201-211. doi:10.1086/524669
22. VFEND (voriconazole) prescribing information. Available online:http://labeling.pfizer.com/ShowLabeling.aspx? id=618 (Accessed onMarch 10, 2023).
23. Abuhelwa AY, Foster DJ, Mudge S, Hayes D, Upton RN. Populationpharmacokinetic modeling of itraconazole and hydroxyitraconazolefor oral SUBA-itraconazole and sporanox capsule formulations inhealthy subjects in fed and fasted states. Antimicrob Agents Chemother.2015;59(9):5681-5696. doi:10.1128/AAC.00973-15
24. Van Peer A, Woestenborghs R, Heykants J, Gasparini R, GauwenberghG. The effects of food and dose on the oral systemic availability ofitraconazole in healthy subjects. Eur J Clin Pharmacol. 1989;36(4):423-426. doi:10.1007/BF00558308
25. Haria M, Bryson HM, Goa KL. Itraconazole. A reappraisal of itspharmacological properties and therapeutic use in the managementof superficial fungal infections [published correction appears in Drugs1996 Aug;52(2):253]. Drugs. 1996;51(4):585-620. doi:10.2165/00003495-199651040-00006
26. Krishna G, Ma L, Martinho M, O’Mara E. Single-dose phase I studyto evaluate the pharmacokinetics of posaconazole in new tablet andcapsule formulations relative to oral suspension. Antimicrob AgentsChemother. 2012;56(8):4196-4201. doi:10.1128/AAC.00222-12
27. Krieter P, Flannery B, Musick T, Gohdes M, Martinho M, Courtney R.Disposition of posaconazole following single-dose oral administrationin healthy subjects. Antimicrob Agents Chemother. 2004;48(9):3543-3551. doi:10.1128/AAC.48.9.3543-3551.2004
28. Schmitt-Hoffmann A, Roos B, Heep M, et al. Single-ascending-dosepharmacokinetics and safety of the novel broad-spectrum antifungaltriazole BAL4815 after intravenous infusions (50, 100, and 200milligrams) and oral administrations (100, 200, and 400 milligrams)of its prodrug, BAL8557, in healthy volunteers. Antimicrob AgentsChemother. 2006;50(1):279-285. doi:10.1128/AAC.50.1.279-285.2006
29. Saag MS, Powderly WG, Cloud GA, et al. Comparison of amphotericinB with fluconazole in the treatment of acute AIDS-associatedcryptococcal meningitis. The NIAID Mycoses Study Group andthe AIDS Clinical Trials Group. N Engl J Med. 1992;326(2):83-89.doi:10.1056/NEJM199201093260202
30. Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazoleprophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study. J Infect Dis.1995;171(6):1545-1552. doi:10.1093/infdis/171.6.1545
31. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versusamphotericin B for primary therapy of invasive aspergillosis. N Engl JMed. 2002;347(6):408-415. doi:10.1056/NEJMoa020191
32. Smith DE, Midgley J, Allan M, Connolly GM, Gazzard BG. Itraconazoleversus ketaconazole in the treatment of oral and oesophagealcandidosis in patients infected with HIV. AIDS. 1991;5(11):1367-1371.doi:10.1097/00002030-199111000-00014
33. De Beule K, De Doncker P, Cauwenbergh G, et al. The treatment ofaspergillosis and aspergilloma with itraconazole, clinical results of anopen international study (1982-1987). Mycoses. 1988;31(9):476-485.doi:10.1111/j.1439-0507.1988.tb03653.x
34. Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazolefor prophylaxis in severe graft-versus-host disease [publishedcorrection appears in N Engl J Med. 2007 Jul 26;357(4):428]. N Engl JMed. 2007;356(4):335-347. doi:10.1056/NEJMoa061098.
35. Vazquez JA, Skiest DJ, Nieto L, et al. A multicenter randomized trialevaluating posaconazole versus fluconazole for the treatment oforopharyngeal candidiasis in subjects with HIV/AIDS. Clin Infect Dis.2006;42(8):1179-1186. doi:10.1086/501457
36. Maertens JA, Raad II, Marr KA, et al. Isavuconazole versus voriconazolefor primary treatment of invasive mould disease caused by Aspergillusand other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760-769.doi:10.1016/S0140-6736(15)01159-9
37. Marty FM, Ostrosky-Zeichner L, Cornely OA, et al. Isavuconazoletreatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828-837. doi:10.1016/S1473-3099(16)00071-2
38. Vandewoude K, Vogelaers D, Decruyenaere J, et al. Concentrations inplasma and safety of 7 days of intravenous itraconazole followed by 2weeks of oral itraconazole solution in patients in intensive care units.Antimicrob Agents Chemother. 1997;41(12):2714-2718. doi:10.1128/AAC.41.12.2714
39. Clancy CJ, Nguyen MH (2020). Antifungal drugs: echinocandins. In:Mandell, Douglas, and Bennett’s Principles and Practice of InfectiousDiseases.Ed: John E. Bennett, Raphael Dolin, Martin J. Blaiser, NinthEdition, Elsevier, Philadelphia, p: 509-514
40. Cabib E, Roh DH, Schmidt M, Crotti LB, Varma A. The yeast cell walland septum as paradigms of cell growth and morphogenesis. J BiolChem. 2001;276(23):19679-19682. doi:10.1074/jbc.R000031200
41. Kurtz MB, Heath IB, Marrinan J, Dreikorn S, Onishi J, Douglas C.Morphological effects of lipopeptides against Aspergillus fumigatuscorrelate with activities against (1,3)-beta-D-glucan synthase[published correction appears in Antimicrob Agents Chemother 1994Oct;38(10):2516]. Antimicrob Agents Chemother. 1994;38(7):1480-1489.doi:10.1128/AAC.38.7.1480
42. Denning DW. Echinocandin antifungal drugs. Lancet.2003;362(9390):1142-1151. doi:10.1016/S0140-6736(03)14472-8
43. Dodds Ashley ES, Lewis R, Lewis JS, Martin C, Andes D. Pharmacologyof systemic antifungal agents. Clin Infect Dis. 2006;43:S28-S39.10.1086/504492
44. Wagner C, Graninger W, Presterl E, Joukhadar C. The echinocandins:comparison of their pharmacokinetics, pharmacodynamics and clinicalapplications. Pharmacology. 2006;78(4):161-177. doi:10.1159/000096348
45. Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versusfluconazole for invasive candidiasis. N Engl J Med. 2007;356(24):2472-2482. doi:10.1056/NEJMoa066906
46. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis:clinical practice guidelines of the Infectious Diseases Society ofAmerica. Clin Infect Dis. 2008;46(3):327-360. doi:10.1086/525258
47. Colton B (2020). Antifungal drugs: flucytosine. In: Mandell, Douglas,and Bennett’s Principles and Practice of Infectious Diseases.Ed: JohnE. Bennett, Raphael Dolin, Martin J. Blaiser, Ninth Edition, Elsevier,Philadelphia, p: 515-518
48. Vanden Bossche H, Dromer F, Improvisi I, Lozano-Chiu M, Rex JH,Sanglard D. Antifungal drug resistance in pathogenic fungi. MedMycol. 1998;36 Suppl 1:119-128.
49. Patel R. Antifungal agents. Part I. Amphotericin B preparationsand flucytosine. Mayo Clin Proc. 1998;73(12):1205-1225.doi:10.4065/73.12.1205
Article available in :
Volume 1, Issue 2, 2023
Page : 41-46
https://doi.org/10.51271/JCHOR-0010
Article Information
Received : 17 May 2023
Accepted : 24 May 2023
Published : 29 May 2023
Corresponding Author :

İlknur Akkuş: Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey

[email protected]
Citation : Akkuş İ, Kaçmaz B. Antifungal drugs. J Curr Hematol Oncol Res. 2023;1(2):41-46.

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