抗真菌感染药物的研究进展
Research and Development of Antifungal Drugs
DOI: 10.12677/hjbm.2026.161014, PDF,   
作者: 陈庆叶, 阮奔放*:浙江工业大学药学院,浙江 杭州
关键词: 抗真菌药物耐药性新药药物剂型Antifungal Drugs Drug Resistance New Drugs Drug Dosage Form
摘要: 真菌作为自然界中广泛存在的微生物,在特定条件下会突破人体防御屏障引发感染。随着侵袭性真菌感染的病例日益增加,病原真菌耐药性愈发严重,人们开始意识到抑制真菌感染的必要性。本文将主要介绍现有的抗真菌药物以及几种新型的还在研究阶段的抗真菌药物,并对已上市的药物进行剂型总结与分析。
Abstract: Fungi, as microorganisms widely distributed in nature, can breach the human body’s defense barriers and trigger infections under specific circumstances. With the escalating number of cases of invasive fungal infections and the increasingly severe drug resistance of pathogenic fungi, there is a growing awareness of the necessity to inhibit fungal infections. This paper will primarily present the existing antifungal drugs and several novel antifungal agents still in the research phase. Additionally, it will conduct a summary and analysis of the dosage forms of the commercially available drugs.
文章引用:陈庆叶, 阮奔放. 抗真菌感染药物的研究进展[J]. 生物医学, 2026, 16(1): 128-141. https://doi.org/10.12677/hjbm.2026.161014

参考文献

[1] Perfect, J.R. (2017) The Antifungal Pipeline: A Reality Check. Nature Reviews Drug Discovery, 16, 603-616. [Google Scholar] [CrossRef] [PubMed]
[2] Denning, D.W. (2024) Global Incidence and Mortality of Severe Fungal Disease. The Lancet Infectious Diseases, 24, e428-e438. [Google Scholar] [CrossRef] [PubMed]
[3] Kupferschmidt, K. (2019) New Drugs Target Growing Threat of Fatal Fungi. Science, 366, 407. [Google Scholar] [CrossRef] [PubMed]
[4] Anderson, T.M., Clay, M.C., Cioffi, A.G., Diaz, K.A., Hisao, G.S., Tuttle, M.D., et al. (2014) Amphotericin Forms an Extramembranous and Fungicidal Sterol Sponge. Nature Chemical Biology, 10, 400-406. [Google Scholar] [CrossRef] [PubMed]
[5] Belenky, P., Camacho, D. and Collins, J.J. (2013) Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway. Cell Reports, 3, 350-358. [Google Scholar] [CrossRef] [PubMed]
[6] Hamilton-Miller, J.M. (1973) Chemistry and Biology of the Polyene Macrolide Antibiotics. Bacteriological Reviews, 37, 166-196. [Google Scholar] [CrossRef
[7] Lewandowska, A., Soutar, C.P., Greenwood, A.I., Nimerovsky, E., De Lio, A.M., Holler, J.T., et al. (2021) Fungicidal Amphotericin B Sponges Are Assemblies of Staggered Asymmetric Homodimers Encasing Large Void Volumes. Nature Structural & Molecular Biology, 28, 972-981. [Google Scholar] [CrossRef] [PubMed]
[8] Loo, A.S., Muhsin, S.A. and Walsh, T.J. (2013) Toxicokinetic and Mechanistic Basis for the Safety and Tolerability of Liposomal Amphotericin B. Expert Opinion on Drug Safety, 12, 881-895. [Google Scholar] [CrossRef] [PubMed]
[9] Faustino, C. and Pinheiro, L. (2020) Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy. Pharmaceutics, 12, Article 29. [Google Scholar] [CrossRef] [PubMed]
[10] Aguilar-Zapata, D., Petraitiene, R. and Petraitis, V. (2015) Echinocandins: The Expanding Antifungal Armamentarium. Clinical Infectious Diseases, 61, S604-S611. [Google Scholar] [CrossRef] [PubMed]
[11] Denning, D.W. (2003) Echinocandin Antifungal Drugs. The Lancet, 362, 1142-1151. [Google Scholar] [CrossRef] [PubMed]
[12] Alexander, B.D., Johnson, M.D., Pfeiffer, C.D., Jiménez-Ortigosa, C., Catania, J., Booker, R., et al. (2013) Increasing Echinocandin Resistance in Candida Glabrata: Clinical Failure Correlates with Presence of FKS Mutations and Elevated Minimum Inhibitory Concentrations. Clinical Infectious Diseases, 56, 1724-1732. [Google Scholar] [CrossRef] [PubMed]
[13] Salem, H., Ahmed, S.M. and Omar, M.M. (2016) Liposomal Flucytosine Capped with Gold Nanoparticle Formulations for Improved Ocular delivery. Drug Design, Development and Therapy, 10, 277-295. [Google Scholar] [CrossRef] [PubMed]
[14] Fang, X., Li, D., Tangadanchu, V.K.R., Gopala, L., Gao, W. and Zhou, C. (2017) Novel Potentially Antifungal Hybrids of 5-Flucytosine and Fluconazole: Design, Synthesis and Bioactive Evaluation. Bioorganic & Medicinal Chemistry Letters, 27, 4964-4969. [Google Scholar] [CrossRef] [PubMed]
[15] Allen, D., Wilson, D., Drew, R. and Perfect, J. (2015) Azole Antifungals: 35 Years of Invasive Fungal Infection Management. Expert Review of Anti-infective Therapy, 13, 787-798. [Google Scholar] [CrossRef] [PubMed]
[16] Fainstein, V. and Bodey, G.P. (1980) Cardiorespiratory Toxicity Due to Miconazole. Annals of Internal Medicine, 93, 432-433. [Google Scholar] [CrossRef] [PubMed]
[17] Khanna, D. and Bharti, S. (2014) Luliconazole for the Treatment of Fungal Infections: An Evidence-Based Review. Core Evidence, 9, 113-124. [Google Scholar] [CrossRef] [PubMed]
[18] Cha, R. and Sobel, J.D. (2004) Fluconazole for the Treatment of Candidiasis: 15 Years Experience. Expert Review of Anti-infective Therapy, 2, 357-366. [Google Scholar] [CrossRef] [PubMed]
[19] Troke, P.F., Andrews, R.J., Pye, G.W. and Richardson, K. (1990) Fluconazole and Other Azoles: Translation of in Vitro Activity to in Vivo and Clinical Efficacy. Clinical Infectious Diseases, 12, S276-S280. [Google Scholar] [CrossRef] [PubMed]
[20] Anaissie, E.J., Darouiche, R.O., Abi-Said, D., Uzun, O., Mera, J., Gentry, L.O., et al. (1996) Management of Invasive Candidal Infections: Results of a Prospective, Randomized, Multicenter Study of Fluconazole versus Amphotericin B and Review of the Literature. Clinical Infectious Diseases, 23, 964-972. [Google Scholar] [CrossRef] [PubMed]
[21] Dolton, M.J. and McLachlan, A.J. (2014) Optimizing Azole Antifungal Therapy in the Prophylaxis and Treatment of Fungal Infections. Current Opinion in Infectious Diseases, 27, 493-500. [Google Scholar] [CrossRef] [PubMed]
[22] Pound, M.W., Townsend, M.L., Dimondi, V., Wilson, D. and Drew, R.H. (2011) Overview of Treatment Options for Invasive Fungal Infections. Medical Mycology, 49, 561-580. [Google Scholar] [CrossRef] [PubMed]
[23] Lass-Flörl, C. (2011) Triazole Antifungal Agents in Invasive Fungal Infections: A Comparative Review. Drugs, 71, 2405-2419. [Google Scholar] [CrossRef] [PubMed]
[24] Chapman, S.W., Dismukes, W.E., Proia, L.A., Bradsher, R.W., Pappas, P.G., Threlkeld, M.G., et al. (2008) Clinical Practice Guidelines for the Management of Blastomycosis: 2008 Update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 46, 1801-1812. [Google Scholar] [CrossRef] [PubMed]
[25] Stevens, D.A. (1997) Analysis of Compassionate Use Itraconazole Therapy for Invasive Aspergillosis by the NIAID Mycoses Study Group Criteria. Archives of Internal Medicine, 157, 1857-1862. [Google Scholar] [CrossRef] [PubMed]
[26] Johnson, L.B. and Kauffman, C.A. (2003) Voriconazole: A New Triazole Antifungal Agent. Clinical Infectious Diseases, 36, 630-637. [Google Scholar] [CrossRef] [PubMed]
[27] Sabatelli, F., Patel, R., Mann, P.A., Mendrick, C.A., Norris, C.C., Hare, R., et al. (2006) In Vitro Activities of Posaconazole, Fluconazole, Itraconazole, Voriconazole, and Amphotericin B against a Large Collection of Clinically Important Molds and Yeasts. Antimicrobial Agents and Chemotherapy, 50, 2009-2015. [Google Scholar] [CrossRef] [PubMed]
[28] Raad, I.I., Graybill, J.R., Bustamante, A.B., Cornely, O.A., Gaona-Flores, V., Afif, C., et al. (2006) Safety of Long-Term Oral Posaconazole Use in the Treatment of Refractory Invasive Fungal Infections. Clinical Infectious Diseases, 42, 1726-1734. [Google Scholar] [CrossRef] [PubMed]
[29] Leber, R., Fuchsbichler, S., Klobučníková, V., Schweighofer, N., Pitters, E., Wohlfarter, K., et al. (2003) Molecular Mechanism of Terbinafine Resistance in Saccharomycescerevisiae. Antimicrobial Agents and Chemotherapy, 47, 3890-3900. [Google Scholar] [CrossRef] [PubMed]
[30] Thompson III, G.R., Soriano, A., Cornely, O.A., et al. (2023) Rezafungin versus Caspofungin for Treatment of Candidaemia and Invasive Candidiasis (ReSTORE): A Multicentre, Double-Blind, Double-Dummy, Randomised Phase 3 Trial. Lancet, 401, 49-59.
[31] Soriano, A., Honore, P.M., Cornely, O.A., Chayakulkeeree, M., Bassetti, M., Haihui, H., et al. (2024) Treatment Outcomes among Patients with a Positivecandidaculture Close to Randomization Receiving Rezafungin or Caspofungin in the Restore Study. Clinical Infectious Diseases, 79, 672-681. [Google Scholar] [CrossRef] [PubMed]
[32] Maertens, J.A., Thompson III, G.R., Spec, A,. et al. (2025) Olorofim for the Treatment of Invasive Fungal Diseases in Patients with Few or No Therapeutic Options: A Single-Arm, Open-Label, Phase 2b Study. The Lancet Infectious Diseases, 25, 1177-1188.
[33] Georgacopoulos, O., Nunnally, N., Ransom, E., Law, D., Birch, M., Lockhart, S., et al. (2021) In Vitro Activity of Novel Antifungal Olorofim against Filamentous Fungi and Comparison to Eight Other Antifungal Agents. Journal of Fungi, 7, Article 378. [Google Scholar] [CrossRef] [PubMed]
[34] Gebremariam, T., Alkhazraji, S., Gu, Y., Singh, S., Alqarihi, A., Shaw, K.J., et al. (2019) Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis. Antimicrobial Agents and Chemotherapy, 64, e01966-19. [Google Scholar] [CrossRef] [PubMed]
[35] Gebremariam, T., Alkhazraji, S., Alqarihi, A., Wiederhold, N.P., Shaw, K.J., Patterson, T.F., et al. (2020) Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus Arrhizus. Antimicrobial Agents and Chemotherapy, 64, e00178-20. [Google Scholar] [CrossRef] [PubMed]
[36] Pappas, P.G., Vazquez, J.A., Oren, I., Rahav, G., Aoun, M., Bulpa, P., et al. (2023) Clinical Safety and Efficacy of Novel Antifungal, Fosmanogepix, for the Treatment of Candidaemia: Results from a Phase 2 Trial. Journal of Antimicrobial Chemotherapy, 78, 2471-2480. [Google Scholar] [CrossRef] [PubMed]
[37] Vazquez, J.A., Pappas, P.G., Boffard, K., Paruk, F., Bien, P.A., Tawadrous, M., et al. (2023) Clinical Efficacy and Safety of a Novel Antifungal, Fosmanogepix, in Patients with Candidemia Caused by Candida Auris: Results from a Phase 2 Trial. Antimicrobial Agents and Chemotherapy, 67, e01419-22. [Google Scholar] [CrossRef] [PubMed]
[38] Spec, A., Pullman, J., Thompson, G.R., Powderly, W.G., Tobin, E.H., Vazquez, J., et al. (2019) MSG-10: A Phase 2 Study of Oral Ibrexafungerp (SCY-078) Following Initial Echinocandin Therapy in Non-Neutropenic Patients with Invasive Candidiasis. Journal of Antimicrobial Chemotherapy, 74, 3056-3062. [Google Scholar] [CrossRef] [PubMed]
[39] Schwebke, J.R., Sobel, R., Gersten, J.K., Sussman, S.A., Lederman, S.N., Jacobs, M.A., et al. (2021) Ibrexafungerp versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303). Clinical Infectious Diseases, 74, 1979-1985. [Google Scholar] [CrossRef] [PubMed]
[40] Deng, Q., Li, Y., He, W., Chen, T., Liu, N., Ma, L., et al. (2025) A Polyene Macrolide Targeting Phospholipids in the Fungal Cell Membrane. Nature, 640, 743-751. [Google Scholar] [CrossRef] [PubMed]