The rising burden of fungal infections presents a significant challenge to global healthcare, particularly with increasing antifungal resistance limiting treatment efficacy. Early detection and timely intervention remain critical, yet fungal pathogens employ diverse mechanisms to evade host immunity and develop resistance, undermining existing therapeutic options. Limited antifungal options and rising resistance necessitate novel treatment strategies. This review provides a comprehensive overview of conventional antifungal agents, their mechanisms of action, and emerging resistance pathways. Furthermore, it highlights recently approved and investigational antifungal compounds while evaluating innovative approaches such as nanotechnology, drug repurposing, and immunotherapy. Addressing antifungal resistance requires a multifaceted strategy that integrates novel therapeutics, enhanced diagnostic tools, and future research efforts to develop sustainable and effective treatment solutions.

3rd Faculty of Medicine Charles University Ruská 87 100 00 Prague Czech Republic

Department of Biochemistry and Microbiology Faculty of Pharmacy Antioch Syrian Private University Maaret Saidnaya 22734 Syria

Department of Clinical and Experimental Medicine University of Messina 98125 Messina Italy

Department of Clinical Laboratory Sciences College of Applied Medical Sciences Taibah University Madina 41477 Saudi Arabia

Department of Medicine Surgery and Pharmacy Scuola di Specializzazione in Farmacia Ospedaliera University of Sassari 07100 Sassari Italy

Department of Microbiology and Immunology Faculty of Pharmacy Assiut University Assiut 71515 Egypt

Department of Pathology and Laboratory Medicine College of Medicine University of Cincinnati Cincinnati OH 45221 USA

Department of Pharmaceutics Faculty of Pharmacy University of Tabuk Tabuk 71491 Saudi Arabia

Department of Pharmacology and Toxicology Faculty of Pharmacy University of Tabuk Tabuk 71491 Saudi Arabia

Division of Microbiology Immunology and Biotechnology Department of Natural Products and Alternative Medicine Faculty of Pharmacy University of Tabuk Tabuk 71491 Saudi Arabia

Hospital Pharmacy Giovanni Paolo 2 Hospital ASL Gallura 07026 Olbia Italy

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Bahram M., Netherway T. Fungi as mediators linking organisms and ecosystems. FEMS Microbiol. Rev. 2022;46:fuab058. doi: 10.1093/femsre/fuab058. PubMed DOI PMC

Pouris J., Kolyva F., Bratakou S., Vogiatzi C.A., Chaniotis D., Beloukas A. The Role of Fungi in Food Production and Processing. Appl. Sci. 2024;14:5046. doi: 10.3390/app14125046. DOI

Case N.T., Berman J., Blehert D.S., Cramer R.A., Cuomo C., Currie C.R., Ene I.V., Fisher M.C., Fritz-Laylin L.K., Gerstein A.C., et al. The future of fungi: Threats and opportunities. G3. 2022;12:jkac224. doi: 10.1093/g3journal/jkac224. PubMed DOI PMC

Khan M.F., Hof C., Niemcová P., Murphy C.D. Recent advances in fungal xenobiotic metabolism: Enzymes and applications. World J. Microbiol. Biotechnol. 2023;39:296. doi: 10.1007/s11274-023-03737-7. PubMed DOI PMC

Khan M.F., Hof C., Niemcova P., Murphy C.D. Chapter Eleven—Biotransformation of fluorinated drugs and xenobiotics by the model fungus Cunninghamella elegans. In: Stockbridge R.B., editor. Methods in Enzymology. Volume 696. Academic Press; Cambridge, MA, USA: 2024. pp. 251–285. PubMed

Thambugala K.M., Daranagama D.A., Tennakoon D.S., Jayatunga D.P.W., Hongsanan S., Xie N. Humans vs. Fungi: An Overview of Fungal Pathogens against Humans. Pathogens. 2024;13:426. doi: 10.3390/pathogens13050426. PubMed DOI PMC

Centers for Disease Control and Prevention (CDC) Types of Fungal Diseases. [(accessed on 1 January 2024)]; Available online: https://www.cdc.gov/fungal/diseases/index.html.

McCormick T.S., Ghannoum M. Time to Think Antifungal Resistance Increased Antifungal Resistance Exacerbates the Burden of Fungal Infections Including Resistant Dermatomycoses. Pathog. Immun. 2023;8:158–176. doi: 10.20411/pai.v8i2.656. PubMed DOI PMC

Vitiello A., Ferrara F., Boccellino M., Ponzo A., Cimmino C., Comberiati E., Zovi A., Clemente S., Sabbatucci M. Antifungal Drug Resistance: An Emergent Health Threat. Biomedicines. 2023;11:1063. doi: 10.3390/biomedicines11041063. PubMed DOI PMC

Bongomin F., Gago S., Oladele R.O., Denning D.W. Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision. J. Fungi. 2017;3:57. doi: 10.3390/jof3040057. PubMed DOI PMC

Benedict K., Jackson B.R., Chiller T., Beer K.D. Estimation of Direct Healthcare Costs of Fungal Diseases in the United States. Clin. Infect. Dis. 2019;68:1791–1797. doi: 10.1093/cid/ciy776. PubMed DOI PMC

Perlroth J., Choi B., Spellberg B. Nosocomial fungal infections: Epidemiology, diagnosis, and treatment. Med. Mycol. 2007;45:321–346. doi: 10.1080/13693780701218689. PubMed DOI

Kovitwanichkanont T., Chong A.H. Superficial fungal infections. Aust. J. Gen. Pr. 2019;48:706–711. doi: 10.31128/AJGP-05-19-4930. PubMed DOI

von Lilienfeld-Toal M., Wagener J., Einsele H., Cornely O.A., Kurzai O. Invasive Fungal Infection. Dtsch. Arztebl. Int. 2019;116:271–278. doi: 10.3238/arztebl.2019.0271. PubMed DOI PMC

Pasqualotto A.C., Quieroz-Telles F. Histoplasmosis dethrones tuberculosis in Latin America. Lancet Infect. Dis. 2018;18:1058–1060. doi: 10.1016/S1473-3099(18)30373-6. PubMed DOI

Casadevall A. Fungal Diseases in the 21st Century: The Near and Far Horizons. Pathog. Immun. 2018;3:183–196. doi: 10.20411/pai.v3i2.249. PubMed DOI PMC

Webb B.J., Ferraro J.P., Rea S., Kaufusi S., Goodman B.E., Spalding J. Epidemiology and Clinical Features of Invasive Fungal Infection in a US Health Care Network. Open Forum Infect. Dis. 2018;5:ofy187. doi: 10.1093/ofid/ofy187. PubMed DOI PMC

Richardson M.D. Changing patterns and trends in systemic fungal infections. J. Antimicrob. Chemother. 2005;56((Suppl. S1)):i5–i11. doi: 10.1093/jac/dki218. PubMed DOI

Singh N. Trends in the epidemiology of opportunistic fungal infections: Predisposing factors and the impact of antimicrobial use practices. Clin. Infect. Dis. 2001;33:1692–1696. doi: 10.1086/323895. PubMed DOI

Rijnders B.J.A., Schauwvlieghe A.F.A.D., Wauters J. Influenza-Associated Pulmonary Aspergillosis: A Local or Global Lethal Combination? Clin. Infect. Dis. 2020;71:1764–1767. doi: 10.1093/cid/ciaa010. PubMed DOI PMC

Lamoth F. Invasive aspergillosis in coronavirus disease 2019: A practical approach for clinicians. Curr. Opin. Infect. Dis. 2022;35:163–169. doi: 10.1097/QCO.0000000000000812. PubMed DOI PMC

Hoenigl M., Seidel D., Carvalho A., Rudramurthy S.M., Arastehfar A., Gangneux J.P., Nasir N., Bonifaz A., Araiza J., Klimko N., et al. The emergence of COVID-19 associated mucormycosis: A review of cases from 18 countries. Lancet Microbe. 2022;3:e543–e552. doi: 10.1016/S2666-5247(21)00237-8. PubMed DOI PMC

Brown G.D., Netea M.G. Exciting developments in the immunology of fungal infections. Cell Host Microbe. 2012;11:422–424. doi: 10.1016/j.chom.2012.04.010. PubMed DOI

Kovács R., Majoros L. Antifungal lock therapy: An eternal promise or an effective alternative therapeutic approach? Lett. Appl. Microbiol. 2022;74:851–862. doi: 10.1111/lam.13653. PubMed DOI PMC

Shields R.K., Nguyen M.H., Press E.G., Clancy C.J. Abdominal candidiasis is a hidden reservoir of echinocandin resistance. Antimicrob. Agents Chemother. 2014;58:7601–7605. doi: 10.1128/AAC.04134-14. PubMed DOI PMC

Bastos R.W., Rossato L., Goldman G.H., Santos D.A. Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond. PLoS Pathog. 2021;17:e1010073. doi: 10.1371/journal.ppat.1010073. PubMed DOI PMC

Meis J.F., Chowdhary A., Rhodes J.L., Fisher M.C., Verweij P.E. Clinical implications of globally emerging azole resistance in Aspergillus fumigatus. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2016;371:20150460. doi: 10.1098/rstb.2015.0460. PubMed DOI PMC

Fuentefria A.M., Pippi B., Dalla Lana D.F., Donato K.K., de Andrade S.F. Antifungals discovery: An insight into new strategies to combat antifungal resistance. Lett. Appl. Microbiol. 2018;66:2–13. doi: 10.1111/lam.12820. PubMed DOI

Hokken M.W., Zwaan B., Melchers W., Verweij P. Facilitators of adaptation and antifungal resistance mechanisms in clinically relevant fungi. Fungal Genet. Biol. 2019;132:103254. doi: 10.1016/j.fgb.2019.103254. PubMed DOI

Hetta H.F., Ramadan Y.N., Al-Kadmy I.M.S., Ellah N.H.A., Shbibe L., Battah B. Nanotechnology-Based Strategies to Combat Multidrug-Resistant Candida auris Infections. Pathogens. 2023;12:1033. doi: 10.3390/pathogens12081033. PubMed DOI PMC

Zotchev S.B. Polyene macrolide antibiotics and their applications in human therapy. Curr. Med. Chem. 2003;10:211–223. doi: 10.2174/0929867033368448. PubMed DOI

Bates D.W., Su L., Yu D.T., Chertow G.M., Seger D.L., Gomes D.R., Dasbach E.J., Platt R. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clin. Infect. Dis. 2001;32:686–693. doi: 10.1086/319211. PubMed DOI

Herbrecht R., Denning D.W., Patterson T.F., Bennett J.E., Greene R.E., Oestmann J.W., Kern W.V., Marr K.A., Ribaud P., Lortholary O., et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 2002;347:408–415. doi: 10.1056/NEJMoa020191. PubMed DOI

Alexander B.D., Johnson M.D., Pfeiffer C.D., Jiménez-Ortigosa C., Catania J., Booker R., Castanheira M., Messer S.A., Perlin D.S., Pfaller M.A. Increasing echinocandin resistance in Candida glabrata: Clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin. Infect. Dis. 2013;56:1724–1732. doi: 10.1093/cid/cit136. PubMed DOI PMC

Rogers T.R., Verweij P.E., Castanheira M., Dannaoui E., White P.L., Arendrup M.C. Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications. J. Antimicrob. Chemother. 2022;77:2053–2073. doi: 10.1093/jac/dkac161. PubMed DOI PMC

Vermes A., Guchelaar H.-J., Dankert J. Flucytosine: A review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J. Antimicrob. Chemother. 2000;46:171–179. doi: 10.1093/jac/46.2.171. PubMed DOI

Houšť J., Spížek J., Havlíček V. Antifungal drugs. Metabolites. 2020;10:106. doi: 10.3390/metabo10030106. PubMed DOI PMC

Cass A., Finkelstein A., Krespi V. The ion permeability induced in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B. J. Gen. Physiol. 1970;56:100–124. doi: 10.1085/jgp.56.1.100. PubMed DOI PMC

Starzyk J., Gruszecki M., Tutaj K., Luchowski R., Szlazak R., Wasko P., Grudzinski W., Czub J., Gruszecki W.I. Self-association of amphotericin B: Spontaneous formation of molecular structures responsible for the toxic side effects of the antibiotic. J. Phys. Chem. B. 2014;118:13821–13832. doi: 10.1021/jp510245n. PubMed DOI

Mesa-Arango A.C., Scorzoni L., Zaragoza O. It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug. Front. Microbiol. 2012;3:286. doi: 10.3389/fmicb.2012.00286. PubMed DOI PMC

Wang X., Mohammad I.S., Fan L., Zhao Z., Nurunnabi M., Sallam M.A., Wu J., Chen Z., Yin L., He W. Delivery strategies of amphotericin B for invasive fungal infections. Acta Pharm. Sin. B. 2021;11:2585–2604. doi: 10.1016/j.apsb.2021.04.010. PubMed DOI PMC

Sokol-Anderson M.L., Brajtburg J., Medoff G. Amphotericin B-induced oxidative damage and killing of Candida albicans. J. Infect. Dis. 1986;154:76–83. doi: 10.1093/infdis/154.1.76. PubMed DOI

Boukari K., Balme S., Janot J.-M., Picaud F. Towards new insights in the sterol/amphotericin nanochannels formation: A molecular dynamic simulation study. J. Membr. Biol. 2016;249:261–270. doi: 10.1007/s00232-015-9865-y. PubMed DOI

Gray K.C., Palacios D.S., Dailey I., Endo M.M., Uno B.E., Wilcock B.C., Burke M.D. Amphotericin primarily kills yeast by simply binding ergosterol. Proc. Natl. Acad. Sci. USA. 2012;109:2234–2239. doi: 10.1073/pnas.1117280109. PubMed DOI PMC

Anderson T.M., Clay M.C., Cioffi A.G., Diaz K.A., Hisao G.S., Tuttle M.D., Nieuwkoop A.J., Comellas G., Maryum N., Wang S. Amphotericin forms an extramembranous and fungicidal sterol sponge. Nat. Chem. Biol. 2014;10:400–406. doi: 10.1038/nchembio.1496. PubMed DOI PMC

Rivnay B., Wakim J., Avery K., Petrochenko P., Myung J.H., Kozak D., Yoon S., Landrau N., Nivorozhkin A. Critical process parameters in manufacturing of liposomal formulations of amphotericin B. Int. J. Pharm. 2019;565:447–457. doi: 10.1016/j.ijpharm.2019.04.052. PubMed DOI

Marcano R.G.d.J.V., Tominaga T.T., Khalil N.M., Pedroso L.S., Mainardes R.M. Chitosan functionalized poly (ε-caprolactone) nanoparticles for amphotericin B delivery. Carbohydr. Polym. 2018;202:345–354. doi: 10.1016/j.carbpol.2018.08.142. PubMed DOI

Tragiannidis A., Gkampeta A., Vousvouki M., Vasileiou E., Groll A.H. Antifungal agents and the kidney: Pharmacokinetics, clinical nephrotoxicity, and interactions. Expert. Opin. Drug Saf. 2021;20:1061–1074. doi: 10.1080/14740338.2021.1922667. PubMed DOI

Aversa F., Busca A., Candoni A., Cesaro S., Girmenia C., Luppi M., Nosari A.M., Pagano L., Romani L., Rossi G. Liposomal amphotericin B (AmBisome®) at beginning of its third decade of clinical use. J. Chemother. 2017;29:131–143. doi: 10.1080/1120009X.2017.1306183. PubMed DOI

Bulbake U., Doppalapudi S., Kommineni N., Khan W. Liposomal formulations in clinical use: An updated review. Pharmaceutics. 2017;9:12. doi: 10.3390/pharmaceutics9020012. PubMed DOI PMC

Stone N.R., Bicanic T., Salim R., Hope W. Liposomal amphotericin B (AmBisome®): A review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs. 2016;76:485–500. doi: 10.1007/s40265-016-0538-7. PubMed DOI PMC

Adler-Moore J., Proffitt R.T. AmBisome: Liposomal formulation, structure, mechanism of action and pre-clinical experience. J. Antimicrob. Chemother. 2002;49:21–30. doi: 10.1093/jac/49.suppl_1.21. PubMed DOI

Walker L., Sood P., Lenardon M.D., Milne G., Olson J., Jensen G., Wolf J., Casadevall A., Adler-Moore J., Gow N.A. The viscoelastic properties of the fungal cell wall allow traffic of AmBisome as intact liposome vesicles. mBio. 2018;9:e02383-17. doi: 10.1128/mBio.02383-17. PubMed DOI PMC

Readio J.D., Bittman R. Equilibrium binding of amphotericin B and its methyl ester and borate complex to sterols. Biochim. Biophys. Acta (BBA)-Biomembr. 1982;685:219–224. doi: 10.1016/0005-2736(82)90103-1. PubMed DOI

Adler-Moore J., Lewis R.E., Brüggemann R.J.M., Rijnders B.J.A., Groll A.H., Walsh T.J. Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B. Clin. Infect. Dis. 2019;68:S244–S259. doi: 10.1093/cid/ciz064. PubMed DOI PMC

Kelemen H., Orgovan G., Szekely-Szentmiklosi B. The pharmaceutical chemistry of azole antifungals. Acta Pharm. Hung. 2016;86:85–98. PubMed

Lindsay J., Teh B.W., Micklethwaite K., Slavin M. Azole antifungals and new targeted therapies for hematological malignancy. Curr. Opin. Infect. Dis. 2019;32:538–545. doi: 10.1097/QCO.0000000000000611. PubMed DOI

Pristov K., Ghannoum M. Resistance of Candida to azoles and echinocandins worldwide. Clin. Microbiol. Infect. 2019;25:792–798. doi: 10.1016/j.cmi.2019.03.028. PubMed DOI

Abd El-Baky R.M., Sandle T., John J., Abuo-Rahma G.E.-D.A., Hetta H.F. A novel mechanism of action of ketoconazole: Inhibition of the NorA efflux pump system and biofilm formation in multidrug-resistant Staphylococcus aureus. Infect. Drug Resist. 2019;12:1703. doi: 10.2147/IDR.S201124. PubMed DOI PMC

Jangir P., Kalra S., Tanwar S., Bari V.K. Azole resistance in Candida auris: Mechanisms and combinatorial therapy. Apmis. 2023;131:442–462. doi: 10.1111/apm.13336. PubMed DOI

Ledoux M.-P., Guffroy B., Nivoix Y., Simand C., Herbrecht R. Invasive pulmonary aspergillosis. Semin. Respir. Crit. Care Med. 2020;41:080–098. doi: 10.1055/s-0039-3401990. PubMed DOI

Denning D.W. Echinocandin antifungal drugs. Lancet. 2003;362:1142–1151. doi: 10.1016/S0140-6736(03)14472-8. PubMed DOI

Szymański M., Chmielewska S., Czyżewska U., Malinowska M., Tylicki A. Echinocandins—Structure, mechanism of action and use in antifungal therapy. J. Enzym. Inhib. Med. Chem. 2022;37:876–894. doi: 10.1080/14756366.2022.2050224. PubMed DOI PMC

Hoofnagle J.H. Drug-Induced Liver Disease. Elsevier; Amsterdam, The Netherlands: 2013. LiverTox: A website on drug-induced liver injury; pp. 725–732.

Cappelletty D., Eiselstein-McKitrick K. The echinocandins. Pharmacotherapy. 2007;27:369–388. doi: 10.1592/phco.27.3.369. PubMed DOI

Gobernado M., Cantón E. [Anidulafungin] Rev. Esp. Quim. 2008;21:99–114. PubMed

Dowell J.A., Schranz J., Baruch A., Foster G. Safety and Pharmacokinetics of Coadministered Voriconazole and Anidulafungin. J. Clin. Pharmacol. 2005;45:1373–1382. doi: 10.1177/0091270005281234. PubMed DOI

Vazquez J.A. The safety of anidulafungin. Expert. Opin. Drug Saf. 2006;5:751–758. doi: 10.1517/14740338.5.6.751. PubMed DOI

Stover K.R., Farley J.M., Kyle P.B., Cleary J.D. Cardiac toxicity of some echinocandin antifungals. Expert. Opin. Drug Saf. 2014;13:5–14. doi: 10.1517/14740338.2013.829036. PubMed DOI

Stover K.R., Cleary J.D. Cardiac response to centrally administered echinocandin antifungals. J. Pharm. Pharmacol. 2015;67:1279–1283. doi: 10.1111/jphp.12429. PubMed DOI

Vazquez J.A., Sobel J.D. Anidulafungin: A novel echinocandin. Clin. Infect. Dis. 2006;43:215–222. doi: 10.1086/505204. PubMed DOI

Vera-González N., Bailey-Hytholt C.M., Langlois L., de Camargo Ribeiro F., de Souza Santos E.L., Junqueira J.C., Shukla A. Anidulafungin liposome nanoparticles exhibit antifungal activity against planktonic and biofilm Candida albicans. J. Biomed. Mater. Res. Part A. 2020;108:2263–2276. doi: 10.1002/jbm.a.36984. PubMed DOI

Maxfield L., Preuss C.V., Bermudez R. StatPearls. StatPearls Publishing LLC.; Treasure Island, FL, USA: 2022. Terbinafine. PubMed

Bondaryk M., Kurzątkowski W., Staniszewska M. Antifungal agents commonly used in the superficial and mucosal candidiasis treatment: Mode of action and resistance development. Adv. Dermatol. Allergol./Postępy Dermatol. I Alergol. 2013;30:293–301. doi: 10.5114/pdia.2013.38358. PubMed DOI PMC

Delma F.Z., Al-Hatmi A.M.S., Brüggemann R.J.M., Melchers W.J.G., de Hoog S., Verweij P.E., Buil J.B. Molecular Mechanisms of 5-Fluorocytosine Resistance in Yeasts and Filamentous Fungi. J. Fungi. 2021;7:909. doi: 10.3390/jof7110909. PubMed DOI PMC

Stott K.E., Loyse A., Jarvis J.N., Alufandika M., Harrison T.S., Mwandumba H.C., Day J.N., Lalloo D.G., Bicanic T., Perfect J.R., et al. Cryptococcal meningoencephalitis: Time for action. Lancet Infect. Dis. 2021;21:e259–e271. doi: 10.1016/S1473-3099(20)30771-4. PubMed DOI

Singulani J.d.L., Galeane M.C., Ramos M.D., Gomes P.C., Dos Santos C.T., De Souza B.M., Palma M.S., Fusco Almeida A.M., Mendes Giannini M.J.S. Antifungal activity, toxicity, and membranolytic action of a mastoparan analog peptide. Front. Cell. Infect. Microbiol. 2019;9:419. doi: 10.3389/fcimb.2019.00419. PubMed DOI PMC

Domínguez J.M., Kelly V.A., Kinsman O.S., Marriott M.S., Gómez de las Heras F., Martín J.J. Sordarins: A new class of antifungals with selective inhibition of the protein synthesis elongation cycle in yeasts. Antimicrob. Agents Chemother. 1998;42:2274–2278. doi: 10.1128/AAC.42.9.2274. PubMed DOI PMC

Shao Y., Molestak E., Su W., Stankevič M., Tchórzewski M. Sordarin- An anti-fungal antibiotic with a unique modus operandi. Br. J. Pharmacol. 2022;179:1125–1145. doi: 10.1111/bph.15724. PubMed DOI

Olson J.M., Troxell T. StatPearls. StatPearls Publishing LLC.; Treasure Island, FL, USA: 2022. Griseofulvin.

Odom A.R. The triphenylethylenes, a novel class of antifungals. mBio. 2014;5:e01126-14. doi: 10.1128/mBio.01126-14. PubMed DOI PMC

Ben-Ami R., Kontoyiannis D.P. Resistance to Antifungal Drugs. Infect. Dis. Clin. N. Am. 2021;35:279–311. doi: 10.1016/j.idc.2021.03.003. PubMed DOI

Parente-Rocha J.A., Bailão A.M., Amaral A.C., Taborda C.P., Paccez J.D., Borges C.L., Pereira M. Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi. Mediat. Inflamm. 2017;2017:9870679. doi: 10.1155/2017/9870679. PubMed DOI PMC

Beekman C.N., Ene I.V. Short-term evolution strategies for host adaptation and drug escape in human fungal pathogens. PLoS Pathog. 2020;16:e1008519. doi: 10.1371/journal.ppat.1008519. PubMed DOI PMC

Lockhart S.R., Etienne K.A., Vallabhaneni S., Farooqi J., Chowdhary A., Govender N.P., Colombo A.L., Calvo B., Cuomo C.A., Desjardins C.A., et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin. Infect. Dis. 2016;64:134–140. doi: 10.1093/cid/ciw691. PubMed DOI PMC

CDC Candida auris. [(accessed on 1 March 2024)]; Available online: https://www.cdc.gov/candida-auris/index.html.

Vallabhaneni S., Baggs J., Tsay S., Srinivasan A.R., Jernigan J.A., Jackson B.R. Trends in antifungal use in US hospitals, 2006–2012. J. Antimicrob. Chemother. 2018;73:2867–2875. doi: 10.1093/jac/dky270. PubMed DOI

Perfect J.R., Dismukes W.E., Dromer F., Goldman D.L., Graybill J.R., Hamill R.J., Harrison T.S., Larsen R.A., Lortholary O., Nguyen M.H., et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin. Infect. Dis. 2010;50:291–322. doi: 10.1086/649858. PubMed DOI PMC

Pappas P.G., Kauffman C.A., Andes D.R., Clancy C.J., Marr K.A., Ostrosky-Zeichner L., Reboli A.C., Schuster M.G., Vazquez J.A., Walsh T.J., et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2015;62:e1–e50. doi: 10.1093/cid/civ933. PubMed DOI PMC

Ullmann A.J., Aguado J.M., Arikan-Akdagli S., Denning D.W., Groll A.H., Lagrou K., Lass-Flörl C., Lewis R.E., Munoz P., Verweij P.E. Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin. Microbiol. Infect. 2018;24:e1–e38. doi: 10.1016/j.cmi.2018.01.002. PubMed DOI

Lionakis M.S., Lewis R.E., Kontoyiannis D.P. Breakthrough invasive mold infections in the hematology patient: Current concepts and future directions. Clin. Infect. Dis. 2018;67:1621–1630. doi: 10.1093/cid/ciy473. PubMed DOI PMC

Marichal P., Koymans L., Willemsens S., Bellens D., Verhasselt P., Luyten W., Borgers M., Ramaekers F.C.S., Odds F.C., Vanden Bossche H. Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans. Pt 10Microbiology. 1999;145:2701–2713. doi: 10.1099/00221287-145-10-2701. PubMed DOI

Flowers S.A., Colón B., Whaley S.G., Schuler M.A., Rogers P.D. Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans. Antimicrob. Agents Chemother. 2015;59:450–460. doi: 10.1128/AAC.03470-14. PubMed DOI PMC

Morschhäuser J., Barker K.S., Liu T.T., Bla B.W.J., Homayouni R., Rogers P.D. The transcription factor Mrr1p controls expression of the MDR1 efflux pump and mediates multidrug resistance in Candida albicans. PLoS Pathog. 2007;3:e164. doi: 10.1371/journal.ppat.0030164. PubMed DOI PMC

Coste A.T., Karababa M., Ischer F., Bille J., Sanglard D. TAC1, transcriptional activator of CDR genes, is a new transcription factor involved in the regulation of Candida albicans ABC transporters CDR1 and CDR2. Eukaryot. Cell. 2004;3:1639–1652. doi: 10.1128/EC.3.6.1639-1652.2004. PubMed DOI PMC

Pfaller M.A., Diekema D.J., Turnidge J.D., Castanheira M., Jones R.N. Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997-2016. Open Forum Infect. Dis. 2019;6:S79–s94. doi: 10.1093/ofid/ofy358. PubMed DOI PMC

Pais P., Califórnia R., Galocha M., Viana R., Ola M., Cavalheiro M., Takahashi-Nakaguchi A., Chibana H., Butler G., Teixeira M.C. Candida glabrata Transcription Factor Rpn4 Mediates Fluconazole Resistance through Regulation of Ergosterol Biosynthesis and Plasma Membrane Permeability. Antimicrob. Agents Chemother. 2020;64:e00554-20. doi: 10.1128/AAC.00554-20. PubMed DOI PMC

Galocha M., Viana R., Pais P., Silva-Dias A., Cavalheiro M., Miranda I.M., Van Ende M., Souza C.S., Costa C., Branco J., et al. Genomic evolution towards azole resistance in Candida glabrata clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation. Commun. Biol. 2022;5:1118. doi: 10.1038/s42003-022-04087-0. PubMed DOI PMC

Ramage G., Rajendran R., Sherry L., Williams C. Fungal biofilm resistance. Int. J. Microbiol. 2012;2012:528521. doi: 10.1155/2012/528521. PubMed DOI PMC

Khalil M.A., Ahmed F.A., Elkhateeb A.F., Mahmoud E.E., Ahmed M.I., Ahmed R.I., Hosni A., Alghamdi S., Kabrah A., Dablool A.S. Virulence characteristics of biofilm-forming Acinetobacter baumannii in clinical isolates using a Galleria mellonella Model. Microorganisms. 2021;9:2365. doi: 10.3390/microorganisms9112365. PubMed DOI PMC

Nett J.E., Crawford K., Marchillo K., Andes D.R. Role of Fks1p and matrix glucan in Candida albicans biofilm resistance to an echinocandin, pyrimidine, and polyene. Antimicrob. Agents Chemother. 2010;54:3505–3508. doi: 10.1128/AAC.00227-10. PubMed DOI PMC

Segal B.H. Aspergillosis. N. Engl. J. Med. 2009;360:1870–1884. doi: 10.1056/NEJMra0808853. PubMed DOI

Lamoth F., Chung S.J., Damonti L., Alexander B.D. Changing epidemiology of invasive mold infections in patients receiving azole prophylaxis. Clin. Infect. Dis. 2017;64:1619–1621. doi: 10.1093/cid/cix130. PubMed DOI

Warrilow A.G., Melo N., Martel C.M., Parker J.E., Nes W.D., Kelly S.L., Kelly D.E. Expression, purification, and characterization of Aspergillus fumigatus sterol 14-alpha demethylase (CYP51) isoenzymes A and B. Antimicrob. Agents Chemother. 2010;54:4225–4234. doi: 10.1128/AAC.00316-10. PubMed DOI PMC

Snelders E., van der Lee H.A., Kuijpers J., Rijs A.J., Varga J., Samson R.A., Mellado E., Donders A.R., Melchers W.J., Verweij P.E. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 2008;5:e219. doi: 10.1371/journal.pmed.0050219. PubMed DOI PMC

Moore L.C., Brenneman T.B., Waliullah S., Bock C.H., Ali M.E. Multiple Mutations and Overexpression in the CYP51A and B Genes Lead to Decreased Sensitivity of Venturia effusa to Tebuconazole. Curr. Issues Mol. Biol. 2022;44:670–685. doi: 10.3390/cimb44020047. PubMed DOI PMC

Perlin D.S., Rautemaa-Richardson R., Alastruey-Izquierdo A. The global problem of antifungal resistance: Prevalence, mechanisms, and management. Lancet Infect. Dis. 2017;17:e383–e392. doi: 10.1016/S1473-3099(17)30316-X. PubMed DOI

Alastruey-Izquierdo A., Alcazar-Fuoli L., Cuenca-Estrella M. Antifungal susceptibility profile of cryptic species of Aspergillus. Mycopathologia. 2014;178:427–433. doi: 10.1007/s11046-014-9775-z. PubMed DOI

Xiong Q., Hassan S.A., Wilson W.K., Han X.Y., May G.S., Tarrand J.J., Matsuda S.P. Cholesterol import by Aspergillus fumigatus and its influence on antifungal potency of sterol biosynthesis inhibitors. Antimicrob. Agents Chemother. 2005;49:518–524. doi: 10.1128/AAC.49.2.518-524.2005. PubMed DOI PMC

Gold J.A.W., Seagle E.E., Nadle J., Barter D.M., Czaja C.A., Johnston H., Farley M.M., Thomas S., Harrison L.H., Fischer J., et al. Treatment Practices for Adults with Candidemia at 9 Active Surveillance Sites-United States, 2017–2018. Clin. Infect. Dis. 2021;73:1609–1616. doi: 10.1093/cid/ciab512. PubMed DOI PMC

Perlin D.S. Echinocandin Resistance in Candida. Clin. Infect. Dis. 2015;61((Suppl. S6)):S612–S617. doi: 10.1093/cid/civ791. PubMed DOI PMC

Pfaller M.A., Castanheira M., Lockhart S.R., Ahlquist A.M., Messer S.A., Jones R.N. Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata. J. Clin. Microbiol. 2012;50:1199–1203. doi: 10.1128/JCM.06112-11. PubMed DOI PMC

Beyda N.D., John J., Kilic A., Alam M.J., Lasco T.M., Garey K.W. FKS mutant Candida glabrata: Risk factors and outcomes in patients with candidemia. Clin. Infect. Dis. 2014;59:819–825. doi: 10.1093/cid/ciu407. PubMed DOI

Farmakiotis D., Tarrand J.J., Kontoyiannis D.P. Drug-resistant Candida glabrata infection in cancer patients. Emerg. Infect. Dis. 2014;20:1833–1840. doi: 10.3201/eid2011.140685. PubMed DOI PMC

Dudiuk C., Macedo D., Leonardelli F., Theill L., Cabeza M.S., Gamarra S., Garcia-Effron G. Molecular Confirmation of the Relationship between Candida guilliermondii Fks1p Naturally Occurring Amino Acid Substitutions and Its Intrinsic Reduced Echinocandin Susceptibility. Antimicrob. Agents Chemother. 2017;61:e02644-16. doi: 10.1128/AAC.02644-16. PubMed DOI PMC

Garcia-Effron G., Katiyar S.K., Park S., Edlind T.D., Perlin D.S. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob. Agents Chemother. 2008;52:2305–2312. doi: 10.1128/AAC.00262-08. PubMed DOI PMC

Desnos-Ollivier M., Bretagne S., Raoux D., Hoinard D., Dromer F., Dannaoui E. Mutations in the fks1 gene in Candida albicans, C. tropicalis, and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the method of the European Committee on Antibiotic Susceptibility Testing. Antimicrob. Agents Chemother. 2008;52:3092–3098. doi: 10.1128/AAC.00088-08. PubMed DOI PMC

Costa-de-Oliveira S., Marcos Miranda I., Silva R.M., Pinto E.S.A., Rocha R., Amorim A., Gonçalves Rodrigues A., Pina-Vaz C. FKS2 mutations associated with decreased echinocandin susceptibility of Candida glabrata following anidulafungin therapy. Antimicrob. Agents Chemother. 2011;55:1312–1314. doi: 10.1128/AAC.00589-10. PubMed DOI PMC

Wiederhold N.P. Antifungal resistance: Current trends and future strategies to combat. Infect. Drug Resist. 2017;10:249–259. doi: 10.2147/IDR.S124918. PubMed DOI PMC

e Silva A.P., Miranda I.M., Branco J., Oliveira P., Faria-Ramos I., Silva R.M., Rodrigues A.G., Costa-de-Oliveira S. FKS1 mutation associated with decreased echinocandin susceptibility of Aspergillus fumigatus following anidulafungin exposure. Sci. Rep. 2020;10:11976. doi: 10.1038/s41598-020-68706-8. PubMed DOI PMC

Jiménez-Ortigosa C., Moore C., Denning D.W., Perlin D.S. Emergence of echinocandin resistance due to a point mutation in the fks1 gene of Aspergillus fumigatus in a patient with chronic pulmonary aspergillosis. Antimicrob. Agents Chemother. 2017;61:e01277-17. doi: 10.1128/AAC.01277-17. PubMed DOI PMC

Rocha E.M.F., Garcia-Effron G., Park S., Perlin D.S. A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob. Agents Chemother. 2007;51:4174–4176. doi: 10.1128/AAC.00917-07. PubMed DOI PMC

Gardiner R., Souteropoulos P., Park S., Perlin D. Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin. Med. Mycol. 2005;43:S299–S305. doi: 10.1080/13693780400029023. PubMed DOI

Arendrup M.C., Perkhofer S., Howard S.J., Garcia-Effron G., Vishukumar A., Perlin D., Lass-Flörl C. Establishing in vitro-in vivo correlations for Aspergillus fumigatus: The challenge of azoles versus echinocandins. Antimicrob. Agents Chemother. 2008;52:3504–3511. doi: 10.1128/AAC.00190-08. PubMed DOI PMC

Castanheira M., Woosley L.N., Diekema D.J., Messer S.A., Jones R.N., Pfaller M.A. Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains. Antimicrob. Agents Chemother. 2010;54:2655–2659. doi: 10.1128/AAC.01711-09. PubMed DOI PMC

Garcia-Effron G., Lee S., Park S., Cleary J.D., Perlin D.S. Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-beta-D-glucan synthase: Implication for the existing susceptibility breakpoint. Antimicrob. Agents Chemother. 2009;53:3690–3699. doi: 10.1128/AAC.00443-09. PubMed DOI PMC

Garcia-Effron G., Chua D.J., Tomada J.R., DiPersio J., Perlin D.S., Ghannoum M., Bonilla H. Novel FKS mutations associated with echinocandin resistance in Candida species. Antimicrob. Agents Chemother. 2010;54:2225–2227. doi: 10.1128/AAC.00998-09. PubMed DOI PMC

Katiyar S., Pfaller M., Edlind T. Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob. Agents Chemother. 2006;50:2892–2894. doi: 10.1128/AAC.00349-06. PubMed DOI PMC

Thompson G.R., 3rd, Wiederhold N.P., Vallor A.C., Villareal N.C., Lewis J.S., 2nd, Patterson T.F. Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob. Agents Chemother. 2008;52:3783–3785. doi: 10.1128/AAC.00473-08. PubMed DOI PMC

Gomes M.Z., Lewis R.E., Kontoyiannis D.P. Mucormycosis caused by unusual mucormycetes, non-Rhizopus, -Mucor, and -Lichtheimia species. Clin. Microbiol. Rev. 2011;24:411–445. doi: 10.1128/cmr.00056-10. PubMed DOI PMC

Ellis D. Amphotericin B: Spectrum and resistance. J. Antimicrob. Chemother. 2002;49((Suppl. S1)):7–10. doi: 10.1093/jac/49.suppl_1.7. PubMed DOI

Hull C.M., Bader O., Parker J.E., Weig M., Gross U., Warrilow A.G., Kelly D.E., Kelly S.L. Two clinical isolates of Candida glabrata exhibiting reduced sensitivity to amphotericin B both harbor mutations in ERG2. Antimicrob. Agents Chemother. 2012;56:6417–6421. doi: 10.1128/AAC.01145-12. PubMed DOI PMC

Sanglard D., Ischer F., Parkinson T., Falconer D., Bille J. Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Antimicrob. Agents Chemother. 2003;47:2404–2412. doi: 10.1128/AAC.47.8.2404-2412.2003. PubMed DOI PMC

Martel C.M., Parker J.E., Bader O., Weig M., Gross U., Warrilow A.G., Kelly D.E., Kelly S.L. A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B. Antimicrob. Agents Chemother. 2010;54:3578–3583. doi: 10.1128/AAC.00303-10. PubMed DOI PMC

Ballo M.K.S., Rtimi S., Kiwi J., Pulgarin C., Entenza J.M., Bizzini A. Fungicidal activity of copper-sputtered flexible surfaces under dark and actinic light against azole-resistant Candida albicans and Candida glabrata. J. Photochem Photobiol B. 2017;174:229–234. doi: 10.1016/j.jphotobiol.2017.07.030. PubMed DOI

Spengler G., Gajdács M., Donadu M.G., Usai M., Marchetti M., Ferrari M., Mazzarello V., Zanetti S., Nagy F., Kovács R. Evaluation of the Antimicrobial and Antivirulent Potential of Essential Oils Isolated from Juniperus oxycedrus L. ssp. macrocarpa Aerial Parts. Microorganisms. 2022;10:758. doi: 10.3390/microorganisms10040758. PubMed DOI PMC

Donadu M.G., Peralta-Ruiz Y., Usai D., Maggio F., Molina-Hernandez J.B., Rizzo D., Bussu F., Rubino S., Zanetti S., Paparella A., et al. Colombian Essential Oil of Ruta graveolens against Nosocomial Antifungal Resistant Candida Strains. J. Fungi. 2021;7:383. doi: 10.3390/jof7050383. PubMed DOI PMC

Bua A., Usai D., Donadu M.G., Delgado Ospina J., Paparella A., Chaves-Lopez C., Serio A., Rossi C., Zanetti S., Molicotti P. Antimicrobial activity of Austroeupatorium inulaefolium (H.B.K.) against intracellular and extracellular organisms. Nat. Prod. Res. 2018;32:2869–2871. doi: 10.1080/14786419.2017.1385014. PubMed DOI

Rtimi S., Pulgarin C., Sanjines R., Kiwi J. Innovative semi-transparent nanocomposite films presenting photo-switchable behavior and leading to a reduction of the risk of infection under sunlight. RSC Adv. 2013;3:16345–16348. doi: 10.1039/c3ra42762e. DOI

Pinna A., Donadu M.G., Usai D., Dore S., Boscia F., Zanetti S. In Vitro Antimicrobial Activity of a New Ophthalmic Solution Containing Hexamidine Diisethionate 0.05% (Keratosept) Cornea. 2020;39:1415–1418. doi: 10.1097/ICO.0000000000002375. PubMed DOI

Pinna A., Donadu M.G., Usai D., Dore S., D’Amico-Ricci G., Boscia F., Zanetti S. In vitro antimicrobial activity of a new ophthalmic solution containing povidone-iodine 0.6% (IODIM®) Acta Ophthalmol. 2020;98:e178–e180. doi: 10.1111/aos.14243. PubMed DOI

Donadu M.G., Usai D., Marchetti M., Usai M., Mazzarello V., Molicotti P., Montesu M.A., Delogu G., Zanetti S. Antifungal activity of oils macerates of North Sardinia plants against Candida species isolated from clinical patients with candidiasis. Nat. Prod. Res. 2020;34:3280–3284. doi: 10.1080/14786419.2018.1557175. PubMed DOI

Juliano C., Cossu M., Pigozzi P., Rassu G., Giunchedi P. Preparation, in vitro characterization and preliminary in vivo evaluation of buccal polymeric films containing chlorhexidine. AAPS PharmSciTech. 2008;9:1153–1158. doi: 10.1208/s12249-008-9153-6. PubMed DOI PMC

Forsberg K., Woodworth K., Walters M., Berkow E.L., Jackson B., Chiller T., Vallabhaneni S. Candida auris: The recent emergence of a multidrug-resistant fungal pathogen. Med. Mycol. 2018;57:1–12. doi: 10.1093/mmy/myy054. PubMed DOI

Gupta A.K., Foley K.A., Versteeg S.G. New Antifungal Agents and New Formulations Against Dermatophytes. Mycopathologia. 2017;182:127–141. doi: 10.1007/s11046-016-0045-0. PubMed DOI

Koga H., Nanjoh Y., Makimura K., Tsuboi R. In vitro antifungal activities of luliconazole, a new topical imidazole. Med. Mycol. 2009;47:640–647. doi: 10.1080/13693780802541518. PubMed DOI

McCormack P.L. Isavuconazonium: First Global Approval. Drugs. 2015;75:817–822. doi: 10.1007/s40265-015-0398-6. PubMed DOI

Kovanda L.L., Maher R., Hope W.W. Isavuconazonium sulfate: A new agent for the treatment of invasive aspergillosis and invasive mucormycosis. Expert Rev. Clin. Pharmacol. 2016;9:887–897. doi: 10.1080/17512433.2016.1185361. PubMed DOI

Rauseo A.M., Coler-Reilly A., Larson L., Spec A. Hope on the Horizon: Novel Fungal Treatments in Development. Open Forum Infect Dis. 2020;7:ofaa016. doi: 10.1093/ofid/ofaa016. PubMed DOI PMC

Wang L., Zhang M., Guo J., Guo W., Zhong N., Shen H., Cai J., Zhu Z., Wu W. In vitro activities of the tetrazole VT-1161 compared with itraconazole and fluconazole against Cryptococcus and non-albicans Candida species. Mycologia. 2021;113:918–925. doi: 10.1080/00275514.2021.1913949. PubMed DOI

Brand S.R., Sobel J.D., Nyirjesy P., Ghannoum M.A., Schotzinger R.J., Degenhardt T.P. A Randomized Phase 2 Study of VT-1161 for the Treatment of Acute Vulvovaginal Candidiasis. Clin. Infect. Dis. 2021;73:e1518–e1524. doi: 10.1093/cid/ciaa1204. PubMed DOI PMC

Schell W.A., Jones A.M., Garvey E.P., Hoekstra W.J., Schotzinger R.J., Alexander B.D. Fungal CYP51 Inhibitors VT-1161 and VT-1129 Exhibit Strong In Vitro Activity against Candida glabrata and C. krusei Isolates Clinically Resistant to Azole and Echinocandin Antifungal Compounds. Antimicrob. Agents Chemother. 2017;61:e01817-16. doi: 10.1128/AAC.01817-16. PubMed DOI PMC

Wiederhold N.P., Najvar L.K., Garvey E.P., Brand S.R., Xu X., Ottinger E.A., Alimardanov A., Cradock J., Behnke M., Hoekstra W.J., et al. The Fungal Cyp51 Inhibitor VT-1129 Is Efficacious in an Experimental Model of Cryptococcal Meningitis. Antimicrob. Agents Chemother. 2018;62:e01071-18. doi: 10.1128/AAC.01071-18. PubMed DOI PMC

Wiederhold N.P., Lockhart S.R., Najvar L.K., Berkow E.L., Jaramillo R., Olivo M., Garvey E.P., Yates C.M., Schotzinger R.J., Catano G., et al. The Fungal Cyp51-Specific Inhibitor VT-1598 Demonstrates In Vitro and In Vivo Activity against Candida auris. Antimicrob. Agents Chemother. 2019;63:e02233-18. doi: 10.1128/AAC.02233-18. PubMed DOI PMC

Garvey E.P., Sharp A.D., Warn P.A., Yates C.M., Atari M., Thomas S., Schotzinger R.J. The novel fungal CYP51 inhibitor VT-1598 displays classic dose-dependent antifungal activity in murine models of invasive aspergillosis. Med. Mycol. 2020;58:505–513. doi: 10.1093/mmy/myz092. PubMed DOI

Garvey E.P., Sharp A.D., Warn P.A., Yates C.M., Schotzinger R.J. The novel fungal CYP51 inhibitor VT-1598 is efficacious alone and in combination with liposomal amphotericin B in a murine model of Cryptococcal meningitis. J. Antimicrob. Chemother. 2018;73:2815–2822. doi: 10.1093/jac/dky242. PubMed DOI

Wiederhold N.P. Review of T-2307, an Investigational Agent That Causes Collapse of Fungal Mitochondrial Membrane Potential. J. Fungi. 2021;7:130. doi: 10.3390/jof7020130. PubMed DOI PMC

Yamashita K., Miyazaki T., Fukuda Y., Mitsuyama J., Saijo T., Shimamura S., Yamamoto K., Imamura Y., Izumikawa K., Yanagihara K., et al. The Novel Arylamidine T-2307 Selectively Disrupts Yeast Mitochondrial Function by Inhibiting Respiratory Chain Complexes. Antimicrob. Agents Chemother. 2019;63:e00374-19. doi: 10.1128/AAC.00374-19. PubMed DOI PMC

Wiederhold N.P., Najvar L.K., Jaramillo R., Olivo M., Patterson H., Connell A., Fukuda Y., Mitsuyama J., Catano G., Patterson T.F. The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris. Antimicrob. Agents Chemother. 2020;64:e02198-19. doi: 10.1128/AAC.02198-19. PubMed DOI PMC

Wiederhold N.P., Najvar L.K., Fothergill A.W., Bocanegra R., Olivo M., McCarthy D.I., Fukuda Y., Mitsuyama J., Patterson T.F. The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against echinocandin-resistant Candida glabrata. J. Antimicrob. Chemother. 2016;71:692–695. doi: 10.1093/jac/dkv398. PubMed DOI PMC

Abe M., Nakamura S., Kinjo Y., Masuyama Y., Mitsuyama J., Kaku M., Miyazaki Y. Efficacy of T-2307, a novel arylamidine, against ocular complications of disseminated candidiasis in mice. J. Antimicrob. Chemother. 2019;74:1327–1332. doi: 10.1093/jac/dkz020. PubMed DOI

Nishikawa H., Fukuda Y., Mitsuyama J., Tashiro M., Tanaka A., Takazono T., Saijo T., Yamamoto K., Nakamura S., Imamura Y., et al. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: An emerging fungal pathogen. J. Antimicrob. Chemother. 2017;72:1709–1713. doi: 10.1093/jac/dkx020. PubMed DOI PMC

Shields R.K., Kline E.G., Healey K.R., Kordalewska M., Perlin D.S., Nguyen M.H., Clancy C.J. Spontaneous mutational frequency and FKS mutation rates vary by echinocandin agent against Candida glabrata. Antimicrob. Agents Chemother. 2019;63:e01692-18. doi: 10.1128/AAC.01692-18. PubMed DOI PMC

Zimbeck A.J., Iqbal N., Ahlquist A.M., Farley M.M., Harrison L.H., Chiller T., Lockhart S.R. FKS mutations and elevated echinocandin MIC values among Candida glabrata isolates from US population-based surveillance. Antimicrob. Agents Chemother. 2010;54:5042–5047. doi: 10.1128/AAC.00836-10. PubMed DOI PMC

Garcia-Effron G. Rezafungin-Mechanisms of Action, Susceptibility and Resistance: Similarities and Differences with the Other Echinocandins. J. Fungi. 2020;6:262. doi: 10.3390/jof6040262. PubMed DOI PMC

Ong V., Hough G., Schlosser M., Bartizal K., Balkovec J.M., James K.D., Krishnan B.R. Preclinical evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. Antimicrob. Agents Chemother. 2016;60:6872–6879. doi: 10.1128/AAC.00701-16. PubMed DOI PMC

Thompson G.R., Soriano A., Honore P.M., Bassetti M., Cornely O.A., Kollef M., Kullberg B.J., Pullman J., Hites M., Fortun J., et al. Efficacy and safety of rezafungin and caspofungin in candidaemia and invasive candidiasis: Pooled data from two prospective randomised controlled trials. Lancet Infect. Dis. 2024;24:319–328. PubMed

Ong V., James K.D., Smith S., Krishnan B.R. Pharmacokinetics of the novel echinocandin CD101 in multiple animal species. Antimicrob. Agents Chemother. 2017;61:e01626-16. doi: 10.1128/AAC.01626-16. PubMed DOI PMC

Mazur P., Morin N., Baginsky W., El-Sherbeini M., Clemas J.A., Nielsen J.B., Foor F. Differential expression and function of two homologous subunits of yeast 1, 3-beta-D-glucan synthase. Mol. Cell. Biol. 1995;15:5671–5681. doi: 10.1128/MCB.15.10.5671. PubMed DOI PMC

Wiederhold N.P., Locke J.B., Daruwala P., Bartizal K. Rezafungin (CD101) demonstrates potent in vitro activity against Aspergillus, including azole-resistant Aspergillus fumigatus isolates and cryptic species. J. Antimicrob. Chemother. 2018;73:3063–3067. doi: 10.1093/jac/dky280. PubMed DOI

Latgé J.-P., Beauvais A., Chamilos G. The cell wall of the human fungal pathogen Aspergillus fumigatus: Biosynthesis, organization, immune response, and virulence. Annu. Rev. Microbiol. 2017;71:99–116. doi: 10.1146/annurev-micro-030117-020406. PubMed DOI

Jiménez-Ortigosa C., Perez W.B., Angulo D., Borroto-Esoda K., Perlin D.S. De Novo Acquisition of Resistance to SCY-078 in Candida glabrata Involves FKS Mutations That both Overlap and Are Distinct from Those Conferring Echinocandin Resistance. Antimicrob. Agents Chemother. 2017;61:e00833-17. doi: 10.1128/AAC.00833-17. PubMed DOI PMC

Schwebke J.R., Sobel R., Gersten J.K., Sussman S.A., Lederman S.N., Jacobs M.A., Chappell B.T., Weinstein D.L., Moffett A.H., Azie N.E., et al. Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303) Clin. Infect. Dis. 2022;74:1979–1985. doi: 10.1093/cid/ciab750. PubMed DOI PMC

Sobel R., Nyirjesy P., Ghannoum M.A., Delchev D.A., Azie N.E., Angulo D., Harriott I.A., Borroto-Esoda K., Sobel J.D. Efficacy and safety of oral ibrexafungerp for the treatment of acute vulvovaginal candidiasis: A global phase 3, randomised, placebo-controlled superiority study (VANISH 306) BJOG. 2022;129:412–420. doi: 10.1111/1471-0528.16972. PubMed DOI PMC

Nyirjesy P., Schwebke J.R., Angulo D.A., Harriott I.A., Azie N.E., Sobel J.D. Phase 2 Randomized Study of Oral Ibrexafungerp Versus Fluconazole in Vulvovaginal Candidiasis. Clin. Infect. Dis. 2022;74:2129–2135. doi: 10.1093/cid/ciab841. PubMed DOI PMC

Goje O., Sobel R., Nyirjesy P., Goldstein S.R., Spitzer M., Faught B., Larson S., King T., Azie N.E., Angulo D., et al. Oral Ibrexafungerp for Vulvovaginal Candidiasis Treatment: An Analysis of VANISH 303 and VANISH 306. J. Women’s Health. 2022;32:178–186. doi: 10.1089/jwh.2022.0132. PubMed DOI PMC

Wu Y., Zhang M., Yang Y., Ding X., Yang P., Huang K., Hu X., Zhang M., Liu X., Yu H. Structures and mechanism of chitin synthase and its inhibition by antifungal drug Nikkomycin Z. Cell Discov. 2022;8:129. doi: 10.1038/s41421-022-00495-y. PubMed DOI PMC

Sass G., Larwood D.J., Martinez M., Chatterjee P., Xavier M.O., Stevens D.A. Nikkomycin Z against Disseminated Coccidioidomycosis in a Murine Model of Sustained-Release Dosing. Antimicrob. Agents Chemother. 2021;65:e0028521. doi: 10.1128/AAC.00285-21. PubMed DOI PMC

Bentz M.L., Nunnally N., Lockhart S.R., Sexton D.J., Berkow E.L. Antifungal activity of nikkomycin Z against Candida auris. J. Antimicrob. Chemother. 2021;76:1495–1497. doi: 10.1093/jac/dkab052. PubMed DOI

Kovács R., Nagy F., Tóth Z., Bozó A., Balázs B., Majoros L. Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms. Lett. Appl. Microbiol. 2019;69:271–278. doi: 10.1111/lam.13204. PubMed DOI

Nakamura I., Ohsumi K., Takeda S., Katsumata K., Matsumoto S., Akamatsu S., Mitori H., Nakai T. ASP2397 is a novel natural compound that exhibits rapid and potent fungicidal activity against Aspergillus species through a specific transporter. Antimicrob. Agents Chemother. 2019;63:e02689-18. doi: 10.1128/AAC.02689-18. PubMed DOI PMC

Nakamura I., Yoshimura S., Masaki T., Takase S., Ohsumi K., Hashimoto M., Furukawa S., Fujie A. ASP2397: A novel antifungal agent produced by Acremonium persicinum MF-347833. J Antibiot. 2017;70:45–51. doi: 10.1038/ja.2016.107. PubMed DOI

Ikai K., Takesako K., Shiomi K., Moriguchi M., Umeda Y., Yamamoto J., Kato I., Naganawa H. Structure of aureobasidin A. J. Antibiot. 1991;44:925–933. doi: 10.7164/antibiotics.44.925. PubMed DOI

Takesako K., Kuroda H., Inoue T., Haruna F., Yoshikawa Y., Kato I., Uchida K., Hiratani T., Yamaguchi H. Biological properties of aureobasidin A, a cyclic depsipeptide antifungal antibiotic. J. Antibiot. 1993;46:1414–1420. doi: 10.7164/antibiotics.46.1414. PubMed DOI

De Cremer K., Staes I., Delattin N., Cammue B.P., Thevissen K., De Brucker K. Combinatorial drug approaches to tackle Candida albicans biofilms. Expert. Rev. Anti Infect. Ther. 2015;13:973–984. doi: 10.1586/14787210.2015.1056162. PubMed DOI

Fioriti S., Brescini L., Pallotta F., Canovari B., Morroni G., Barchiesi F. Antifungal Combinations against Candida Species: From Bench to Bedside. J. Fungi. 2022;8:1077. doi: 10.3390/jof8101077. PubMed DOI PMC

Vitale R.G. Role of Antifungal Combinations in Difficult to Treat Candida Infections. J. Fungi. 2021;7:731. doi: 10.3390/jof7090731. PubMed DOI PMC

Spitzer M., Robbins N., Wright G.D. Combinatorial strategies for combating invasive fungal infections. Virulence. 2017;8:169–185. doi: 10.1080/21505594.2016.1196300. PubMed DOI PMC

Kim J.H., Cheng L.W., Chan K.L., Tam C.C., Mahoney N., Friedman M., Shilman M.M., Land K.M. Antifungal Drug Repurposing. Antibiotics. 2020;9:812. doi: 10.3390/antibiotics9110812. PubMed DOI PMC

Das R., Kotra K., Singh P., Loh B., Leptihn S., Bajpai U. Alternative Treatment Strategies for Secondary Bacterial and Fungal Infections Associated with COVID-19. Infect. Dis. Ther. 2022;11:53–78. doi: 10.1007/s40121-021-00559-8. PubMed DOI PMC

Wiederhold N.P., Patterson T.F., Srinivasan A., Chaturvedi A.K., Fothergill A.W., Wormley F.L., Ramasubramanian A.K., Lopez-Ribot J.L. Repurposing auranofin as an antifungal: In vitro activity against a variety of medically important fungi. Virulence. 2017;8:138–142. doi: 10.1080/21505594.2016.1196301. PubMed DOI PMC

Butts A., Martin J.A., DiDone L., Bradley E.K., Mutz M., Krysan D.J. Structure-activity relationships for the antifungal activity of selective estrogen receptor antagonists related to tamoxifen. PLoS ONE. 2015;10:e0125927. doi: 10.1371/journal.pone.0125927. PubMed DOI PMC

Sun W., Park Y.D., Sugui J.A., Fothergill A., Southall N., Shinn P., McKew J.C., Kwon-Chung K.J., Zheng W., Williamson P.R. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens. PLoS ONE. 2013;8:e70506. doi: 10.1371/journal.pone.0070506. PubMed DOI PMC

Truong M., Monahan L.G., Carter D.A., Charles I.G. Repurposing drugs to fast-track therapeutic agents for the treatment of cryptococcosis. PeerJ. 2018;6:e4761. doi: 10.7717/peerj.4761. PubMed DOI PMC

Ribeiro N.Q., Costa M.C., Magalhães T.F.F., Carneiro H.C.S., Oliveira L.V., Fontes A.C.L., Santos J.R.A., Ferreira G.F., Araujo G.R.S., Alves V., et al. Atorvastatin as a promising anticryptococcal agent. Int. J. Antimicrob. Agents. 2017;49:695–702. doi: 10.1016/j.ijantimicag.2017.04.005. PubMed DOI

Scriven J.E., Tenforde M.W., Levitz S.M., Jarvis J.N. Modulating host immune responses to fight invasive fungal infections. Curr. Opin. Microbiol. 2017;40:95–103. doi: 10.1016/j.mib.2017.10.018. PubMed DOI PMC

Sam Q.H., Yew W.S., Seneviratne C.J., Chang M.W., Chai L.Y.A. Immunomodulation as Therapy for Fungal Infection: Are We Closer? Front. Microbiol. 2018;9:1612. doi: 10.3389/fmicb.2018.01612. PubMed DOI PMC

WHO. FAO Guidelines for the Evaluation of Probiotics in Food. [(accessed on 26 February 2025)]. Available online: http://www.fao.org/food/food-safety-quality/a-z-index/probiotics/en/

Hasslöf P., Hedberg M., Twetman S., Stecksén-Blicks C. Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli--an in vitro study. BMC Oral. Health. 2010;10:18. doi: 10.1186/1472-6831-10-18. PubMed DOI PMC

Ujaoney S., Chandra J., Faddoul F., Chane M., Wang J., Taifour L., Mamtani M.R., Thakre T.P., Kulkarni H., Mukherjee P., et al. In vitro effect of over-the-counter probiotics on the ability of Candida albicans to form biofilm on denture strips. J. Dent. Hyg. 2014;88:183–189. PubMed

Matsubara V.H., Wang Y., Bandara H., Mayer M.P.A., Samaranayake L.P. Probiotic lactobacilli inhibit early stages of Candida albicans biofilm development by reducing their growth, cell adhesion, and filamentation. Appl. Microbiol. Biotechnol. 2016;100:6415–6426. doi: 10.1007/s00253-016-7527-3. PubMed DOI

Amara A.A., Shibl A. Role of Probiotics in health improvement, infection control and disease treatment and management. Saudi Pharm. J. 2015;23:107–114. doi: 10.1016/j.jsps.2013.07.001. PubMed DOI PMC

Kunyeit L., Kurrey N.K., Anu-Appaiah K.A., Rao R.P. Probiotic Yeasts Inhibit Virulence of Non-albicans Candida Species. mBio. 2019;10:e02307-19. doi: 10.1128/mBio.02307-19. PubMed DOI PMC

Bhatt A.P., Redinbo M.R., Bultman S.J. The role of the microbiome in cancer development and therapy. CA Cancer J. Clin. 2017;67:326–344. doi: 10.3322/caac.21398. PubMed DOI PMC

Ashraf R., Shah N.P. Immune system stimulation by probiotic microorganisms. Crit. Rev. Food Sci. Nutr. 2014;54:938–956. doi: 10.1080/10408398.2011.619671. PubMed DOI

Wu Y., Hu S., Wu C., Gu F., Yang Y. Probiotics: Potential Novel Therapeutics Against Fungal Infections. Front. Cell Infect. Microbiol. 2021;11:793419. doi: 10.3389/fcimb.2021.793419. PubMed DOI PMC

Cavalheiro M., Teixeira M.C. Candida Biofilms: Threats, Challenges, and Promising Strategies. Front. Med. 2018;5:28. doi: 10.3389/fmed.2018.00028. PubMed DOI PMC

Mermel L.A., Allon M., Bouza E., Craven D.E., Flynn P., O’Grady N.P., Raad I.I., Rijnders B.J., Sherertz R.J., Warren D.K. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2009;49:1–45. doi: 10.1086/599376. PubMed DOI PMC

O’Grady N.P., Alexander M., Burns L.A., Dellinger E.P., Garland J., Heard S.O., Lipsett P.A., Masur H., Mermel L.A., Pearson M.L., et al. Guidelines for the prevention of intravascular catheter-related infections. Am. J. Infect. Control. 2011;39:S1–S34. doi: 10.1016/j.ajic.2011.01.003. PubMed DOI

Reitzel R.A., Rosenblatt J., Hirsh-Ginsberg C., Murray K., Chaftari A.M., Hachem R., Raad I. In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections. Antimicrob. Agents Chemother. 2016;60:5175–5181. doi: 10.1128/AAC.00254-16. PubMed DOI PMC

Alonso B., Pérez-Granda M.J., Rodríguez-Huerta A., Rodríguez C., Bouza E., Guembe M. The optimal ethanol lock therapy regimen for treatment of biofilm-associated catheter infections: An in-vitro study. J. Hosp. Infect. 2018;100:e187–e195. doi: 10.1016/j.jhin.2018.04.007. PubMed DOI

Balestrino D., Souweine B., Charbonnel N., Lautrette A., Aumeran C., Traoré O., Forestier C. Eradication of microorganisms embedded in biofilm by an ethanol-based catheter lock solution. Nephrol. Dial. Transpl. 2009;24:3204–3209. doi: 10.1093/ndt/gfp187. PubMed DOI

Li X., Yu B., Li H., Liu Z., Fu X., Jiao P., Wang L. Drug Clues for the Treatment of Fungal Catheter-Related Bloodstream Infection with Antifungal Lock Therapy. Drug Des. Devel Ther. 2025;19:683–701. doi: 10.2147/DDDT.S501664. PubMed DOI PMC

Gudiol C., Nicolae S., Royo-Cebrecos C., Aguilar-Guisado M., Montero I., Martín-Gandul C., Perayre M., Berbel D., Encuentra M., Arnan M., et al. Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: A randomised, double-blinded, placebo-controlled trial (TAURCAT) Trials. 2018;19:264. doi: 10.1186/s13063-018-2647-y. PubMed DOI PMC

van den Bosch C.H., Jeremiasse B., van der Bruggen J.T., Frakking F.N.J., Loeffen Y.G.T., van de Ven C.P., van der Steeg A.F.W., Fiocco M.F., van de Wetering M.D., Wijnen M.H.W.A. The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: A systematic review and meta-analysis. J. Hosp. Infect. 2022;123:143–155. doi: 10.1016/j.jhin.2021.10.022. PubMed DOI

Öncü S. In vitro effectiveness of antifungal lock solutions on catheters infected with Candida species. J. Infect. Chemother. 2011;17:634–639. doi: 10.1007/s10156-011-0224-3. PubMed DOI

Chan A.K.Y., Tsang Y.C., Chu C.H., Tsang C.S.P. Aspirin as an Antifungal-Lock Agent in Inhibition of Candidal Biofilm Formation in Surgical Catheters. Infect. Drug Resist. 2021;14:1427–1433. doi: 10.2147/IDR.S308262. PubMed DOI PMC

Gálvez-Iriqui A.C., Plascencia-Jatomea M., Bautista-Baños S. Lysozymes: Characteristics, mechanism of action and technological applications on the control of pathogenic microorganisms. Rev. Mex. J. Phytopathol. 2020;38:360–383. doi: 10.18781/R.MEX.FIT.2005-6. DOI

Ibrahim H.R., Imazato K., Ono H. Human lysozyme possesses novel antimicrobial peptides within its N-terminal domain that target bacterial respiration. J. Agric. Food Chem. 2011;59:10336–10345. doi: 10.1021/jf2020396. PubMed DOI

Hall A.J., Morroll S., Tighe P., Götz F., Falcone F.H. Human chitotriosidase is expressed in the eye and lacrimal gland and has an antimicrobial spectrum different from lysozyme. Microbes Infect. 2008;10:69–78. doi: 10.1016/j.micinf.2007.10.007. PubMed DOI

Cho W.S., Kim T.H., Lee H.M., Lee S.H., Lee S.H., Yoo J.H., Kim Y.S., Lee S.H. Increased expression of acidic mammalian chitinase and chitotriosidase in the nasal mucosa of patients with allergic rhinitis. Laryngoscope. 2010;120:870–875. doi: 10.1002/lary.20863. PubMed DOI

Samaranayake Y.H., Samaranayake L.P., Wu P.C., So M. The antifungal effect of lactoferrin and lysozyme on Candida krusei and Candida albicans. Apmis. 1997;105:875–883. doi: 10.1111/j.1699-0463.1997.tb05097.x. PubMed DOI

Fernandes K.E., Carter D.A. The Antifungal Activity of Lactoferrin and Its Derived Peptides: Mechanisms of Action and Synergy with Drugs against Fungal Pathogens. Front. Microbiol. 2017;8:2. doi: 10.3389/fmicb.2017.00002. PubMed DOI PMC

Takakura N., Wakabayashi H., Ishibashi H., Teraguchi S., Tamura Y., Yamaguchi H., Abe S. Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrob. Agents Chemother. 2003;47:2619–2623. doi: 10.1128/AAC.47.8.2619-2623.2003. PubMed DOI PMC

Adeyemi O.S., Arowolo A.T., Hetta H.F., Al-Rejaie S., Rotimi D., Batiha G.E.-S. Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase of Trypanosoma brucei. Molecules. 2020;25:3432. doi: 10.3390/molecules25153432. PubMed DOI PMC

Tomee J.F., Hiemstra P.S., Heinzel-Wieland R., Kauffman H.F. Antileukoprotease: An endogenous protein in the innate mucosal defense against fungi. J. Infect. Dis. 1997;176:740–747. doi: 10.1086/514098. PubMed DOI

Melo M.N., Ferre R., Castanho M.A. Antimicrobial peptides: Linking partition, activity and high membrane-bound concentrations. Nat. Rev. Microbiol. 2009;7:245–250. doi: 10.1038/nrmicro2095. PubMed DOI

Jia F., Wang J., Peng J., Zhao P., Kong Z., Wang K., Yan W., Wang R. The in vitro, in vivo antifungal activity and the action mode of Jelleine-I against Candida species. Amino Acids. 2018;50:229–239. doi: 10.1007/s00726-017-2507-1. PubMed DOI

Wagener J., Schneider J.J., Baxmann S., Kalbacher H., Borelli C., Nuding S., Küchler R., Wehkamp J., Kaeser M.D., Mailänder-Sanchez D., et al. A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation. J. Investig. Dermatol. 2013;133:144–153. doi: 10.1038/jid.2012.254. PubMed DOI PMC

Selsted M.E., Ouellette A.J. Mammalian defensins in the antimicrobial immune response. Nat. Immunol. 2005;6:551–557. doi: 10.1038/ni1206. PubMed DOI

Krishnakumari V., Rangaraj N., Nagaraj R. Antifungal activities of human beta-defensins HBD-1 to HBD-3 and their C-terminal analogs Phd1 to Phd3. Antimicrob. Agents Chemother. 2009;53:256–260. doi: 10.1128/AAC.00470-08. PubMed DOI PMC

Thevissen K., Kristensen H.H., Thomma B.P., Cammue B.P., François I.E. Therapeutic potential of antifungal plant and insect defensins. Drug Discov. Today. 2007;12:966–971. doi: 10.1016/j.drudis.2007.07.016. PubMed DOI

Schittek B., Hipfel R., Sauer B., Bauer J., Kalbacher H., Stevanovic S., Schirle M., Schroeder K., Blin N., Meier F., et al. Dermcidin: A novel human antibiotic peptide secreted by sweat glands. Nat. Immunol. 2001;2:1133–1137. doi: 10.1038/ni732. PubMed DOI

Arai S., Yoshino T., Fujimura T., Maruyama S., Nakano T., Mukuno A., Sato N., Katsuoka K. Mycostatic effect of recombinant dermcidin against Trichophyton rubrum and reduced dermcidin expression in the sweat of tinea pedis patients. J. Dermatol. 2015;42:70–76. doi: 10.1111/1346-8138.12664. PubMed DOI

van Eijk M., Boerefijn S., Cen L., Rosa M., Morren M.J.H., van der Ent C.K., Kraak B., Dijksterhuis J., Valdes I.D., Haagsman H.P., et al. Cathelicidin-inspired antimicrobial peptides as novel antifungal compounds. Med. Mycol. 2020;58:1073–1084. doi: 10.1093/mmy/myaa014. PubMed DOI PMC

Benincasa M., Scocchi M., Pacor S., Tossi A., Nobili D., Basaglia G., Busetti M., Gennaro R. Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. J. Antimicrob. Chemother. 2006;58:950–959. doi: 10.1093/jac/dkl382. PubMed DOI

Bezerra L.P., Freitas C.D.T., Silva A.F.B., Amaral J.L., Neto N.A.S., Silva R.G.G., Parra A.L.C., Goldman G.H., Oliveira J.T.A., Mesquita F.P., et al. Synergistic Antifungal Activity of Synthetic Peptides and Antifungal Drugs against Candida albicans and C. parapsilosis Biofilms. Antibiotics. 2022;11:553. doi: 10.3390/antibiotics11050553. PubMed DOI PMC

Aguiar T.K.B., Neto N.A.S., Freitas C.D.T., Silva A.F.B., Bezerra L.P., Malveira E.A., Branco L.A.C., Mesquita F.P., Goldman G.H., Alencar L.M.R., et al. Antifungal Potential of Synthetic Peptides against Cryptococcus neoformans: Mechanism of Action Studies Reveal Synthetic Peptides Induce Membrane-Pore Formation, DNA Degradation, and Apoptosis. Pharmaceutics. 2022;14:1678. doi: 10.3390/pharmaceutics14081678. PubMed DOI PMC

Sharma K., Aaghaz S., Maurya I.K., Rudramurthy S.M., Singh S., Kumar V., Tikoo K., Jain R. Antifungal evaluation and mechanistic investigations of membrane active short synthetic peptides-based amphiphiles. Bioorg Chem. 2022;127:106002. doi: 10.1016/j.bioorg.2022.106002. PubMed DOI

Abd Ellah N.H., Ahmed E.A., Abd-Ellatief R.B., Ali M.F., Zahran A.M., Hetta H.F. Metoclopramide nanoparticles modulate immune response in a diabetic rat model: Association with regulatory T cells and proinflammatory cytokines. Int. J. Nanomed. 2019;14:2383. doi: 10.2147/IJN.S196842. PubMed DOI PMC

Abd Ellah N.H., Gad S.F., Muhammad K., E Batiha G., Hetta H.F. Nanomedicine as a promising approach for diagnosis, treatment and prophylaxis against COVID-19. Nanomedicine. 2020;15:2085–2102. doi: 10.2217/nnm-2020-0247. PubMed DOI PMC

Abd Ellah N.H., Tawfeek H.M., John J., Hetta H.F. Nanomedicine as a future therapeutic approach for Hepatitis C virus. Nanomedicine. 2019;14:1471–1491. doi: 10.2217/nnm-2018-0348. PubMed DOI

Abdellatif A.A., Tawfeek H.M., Abdelfattah A., Batiha G.E.-S., Hetta H.F. Recent updates in COVID-19 with emphasis on inhalation therapeutics: Nanostructured and targeting systems. J. Drug Deliv. Sci. Technol. 2021;63:102435. doi: 10.1016/j.jddst.2021.102435. PubMed DOI PMC

Abid S.A., Muneer A.A., Al-Kadmy I.M., Sattar A.A., Beshbishy A.M., Batiha G.E.-S., Hetta H.F. Biosensors as a future diagnostic approach for COVID-19. Life Sci. 2021;273:119117. doi: 10.1016/j.lfs.2021.119117. PubMed DOI PMC

Chaturvedi V.K., Yadav N., Rai N.K., Ellah N.H.A., Bohara R.A., Rehan I.F., Marraiki N., Batiha G.E.-S., Hetta H.F., Singh M. Pleurotus sajor-caju-mediated synthesis of silver and gold nanoparticles active against colon cancer cell lines: A new era of herbonanoceutics. Molecules. 2020;25:3091. doi: 10.3390/molecules25133091. PubMed DOI PMC

Eid A.M., Fouda A., Niedbała G., Hassan S.E.-D., Salem S.S., Abdo A.M., Hetta H.F., Shaheen T.I. Endophytic Streptomyces laurentii mediated green synthesis of Ag-NPs with antibacterial and anticancer properties for developing functional textile fabric properties. Antibiotics. 2020;9:641. doi: 10.3390/antibiotics9100641. PubMed DOI PMC

Hetta H.F., Ramadan Y.N., Al-Harbi A.I., Ahmed E.A., Battah B., Abd Ellah N.H., Zanetti S., Donadu M.G. Nanotechnology as a Promising Approach to Combat Multidrug Resistant Bacteria: A Comprehensive Review and Future Perspectives. Biomedicines. 2023;11:413. doi: 10.3390/biomedicines11020413. PubMed DOI PMC

Sayad R., Abdelsabour H.A., Farhat S.M., Omer N.G., Ahmed M.M., Elsayh I.K., Ibrahim I.H., Algammal A.M., AL-Kadmy I.M.S., Batiha G.E.-S., et al. Applications of nanotechnology in the fight against coronavirus disease 2019. Rev. Res. Med. Microbiol. 2023;34:153–166. doi: 10.1097/MRM.0000000000000335. DOI

Gupta P., Meher M.K., Tripathi S., Poluri K.M. Nanoformulations for dismantling fungal biofilms: The latest arsenals of antifungal therapy. Mol. Asp. Med. 2024;98:101290. doi: 10.1016/j.mam.2024.101290. PubMed DOI

Izadi A., Paknia F., Roostaee M., Mousavi S.A.A., Barani M. Advancements in nanoparticle-based therapies for multidrug-resistant candidiasis infections: A comprehensive review. Nanotechnology. 2024;35:332001. doi: 10.1088/1361-6528/ad4bed. PubMed DOI

Du W., Gao Y., Liu L., Sai S., Ding C. Striking Back against Fungal Infections: The Utilization of Nanosystems for Antifungal Strategies. Int. J. Mol. Sci. 2021;22:10104. doi: 10.3390/ijms221810104. PubMed DOI PMC

Mathur M., Devi V.K. Potential of novel drug delivery systems in the management of topical candidiasis. J. Drug Target. 2017;25:685–703. doi: 10.1080/1061186X.2017.1331352. PubMed DOI

Abo-Shama U.H., El-Gendy H., Mousa W.S., Hamouda R.A., Yousuf W.E., Hetta H.F., Abdeen E.E. Synergistic and antagonistic effects of metal nanoparticles in combination with antibiotics against some reference strains of pathogenic microorganisms. Infect. Drug Resist. 2020;13:351. doi: 10.2147/IDR.S234425. PubMed DOI PMC

Hetta H.F., Al-Kadmy I., Khazaal S.S., Abbas S., Suhail A., El-Mokhtar M.A., Ellah N.H.A., Ahmed E.A., Abd-Ellatief R.B., El-Masry E.A. Antibiofilm and antivirulence potential of silver nanoparticles against multidrug-resistant Acinetobacter baumannii. Sci. Rep. 2021;11:10751. doi: 10.1038/s41598-021-90208-4. PubMed DOI PMC

Saleh H., Nassar A.M., Noreldin A.E., Samak D., Elshony N., Wasef L., Elewa Y.H., Hassan S.M., Saati A.A., Hetta H.F. Chemo-protective potential of cerium oxide nanoparticles against fipronil-induced oxidative stress, apoptosis, inflammation and reproductive dysfunction in male white albino rats. Molecules. 2020;25:3479. doi: 10.3390/molecules25153479. PubMed DOI PMC

Wani I.A., Ahmad T., Manzoor N. Size and shape dependant antifungal activity of gold nanoparticles: A case study of Candida. Colloids Surf. B Biointerfaces. 2013;101:162–170. doi: 10.1016/j.colsurfb.2012.06.005. PubMed DOI

Shaikh S., Nazam N., Rizvi S.M.D., Ahmad K., Baig M.H., Lee E.J., Choi I. Mechanistic Insights into the Antimicrobial Actions of Metallic Nanoparticles and Their Implications for Multidrug Resistance. Int. J. Mol. Sci. 2019;20:2468. doi: 10.3390/ijms20102468. PubMed DOI PMC

Huang T., Li X., Maier M., O’Brien-Simpson N.M., Heath D.E., O’Connor A.J. Using inorganic nanoparticles to fight fungal infections in the antimicrobial resistant era. Acta Biomater. 2023;158:56–79. doi: 10.1016/j.actbio.2023.01.019. PubMed DOI

Rahimi H., Roudbarmohammadi S., Delavari H.H., Roudbary M. Antifungal effects of indolicidin-conjugated gold nanoparticles against fluconazole-resistant strains of Candida albicans isolated from patients with burn infection. Int. J. Nanomed. 2019;14:5323–5338. doi: 10.2147/IJN.S207527. PubMed DOI PMC

Jebali A., Hajjar F.H., Hekmatimoghaddam S., Kazemi B., De La Fuente J.M., Rashidi M. Triangular gold nanoparticles conjugated with peptide ligands: A new class of inhibitor for Candida albicans secreted aspartyl proteinase. Biochem. Pharmacol. 2014;90:349–355. doi: 10.1016/j.bcp.2014.05.020. PubMed DOI

Selvaraj M., Pandurangan P., Ramasami N., Rajendran S.B., Sangilimuthu S.N., Perumal P. Highly Potential Antifungal Activity of Quantum-Sized Silver Nanoparticles Against Candida albicans. Appl. Biochem. Biotechnol. 2014;173:55–66. doi: 10.1007/s12010-014-0782-9. PubMed DOI

Al Aboody M.S. Silver/silver chloride (Ag/AgCl) nanoparticles synthesized from Azadirachta indica lalex and its antibiofilm activity against fluconazole resistant Candida tropicalis. Artif. Cells Nanomed. Biotechnol. 2019;47:2107–2113. doi: 10.1080/21691401.2019.1620257. PubMed DOI

Rónavári A., Igaz N., Gopisetty M.K., Szerencsés B., Kovács D., Papp C., Vágvölgyi C., Boros I.M., Kónya Z., Kiricsi M., et al. Biosynthesized silver and gold nanoparticles are potent antimycotics against opportunistic pathogenic yeasts and dermatophytes. Int. J. Nanomed. 2018;13:695–703. doi: 10.2147/IJN.S152010. PubMed DOI PMC

Bharti S., Singh B., Kumar S., Kumar R., Kumar J. Synthesis of bio-stabilized silver nanoparticles using Roccella montagnei, their anticandidal capacities & potential to inhibit the virulence factors in fluconazole-resistant Candida albicans. World J. Microbiol. Biotechnol. 2024;40:158. doi: 10.1007/s11274-024-03928-w. PubMed DOI

Siddiqi K.S., Ur Rahman A., Tajuddin. Husen, A Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes. Nanoscale Res. Lett. 2018;13:141. doi: 10.1186/s11671-018-2532-3. PubMed DOI PMC

Nazari R. Synergistic antifungal effect of fluconazole combined with ZnO nanoparticles against Candida albicans strains from vaginal candidiasis. Med. Lab. J. 2020;14:26–32.

Manzano M., Vallet-Regí M. Mesoporous silica nanoparticles for drug delivery. Adv. Funct. Mater. 2020;30:1902634. doi: 10.1002/adfm.201902634. DOI

Montazeri M., Razzaghi-Abyaneh M., Nasrollahi S., Maibach H., Nafisi S. Enhanced topical econazole antifungal efficacy by amine-functionalized silica nanoparticles. Bull. Mater. Sci. 2020;43:13. doi: 10.1007/s12034-019-1974-2. DOI

Mas N., Galiana I., Hurtado S., Mondragón L., Bernardos A., Sancenón F., Marcos M.D., Amorós P., Abril-Utrillas N., Martínez-Máñez R., et al. Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles. Int. J. Nanomed. 2014;9:2597–2606. doi: 10.2147/ijn.s59654. PubMed DOI PMC

Kamaly N., Xiao Z., Valencia P.M., Radovic-Moreno A.F., Farokhzad O.C. Targeted polymeric therapeutic nanoparticles: Design, development and clinical translation. Chem. Soc. Rev. 2012;41:2971–3010. doi: 10.1039/c2cs15344k. PubMed DOI PMC

Abd El-Aziz F.E.-Z.A., Hetta H.F., Abdelhamid B.N., Abd Ellah N.H. Antibacterial and wound-healing potential of PLGA/spidroin nanoparticles: A study on earthworms as a human skin model. Nanomedicine. 2022;17:353–365. doi: 10.2217/nnm-2021-0325. PubMed DOI

Hetta H.F., Ahmed E.A., Hemdan A.G., El-Deek H.E., Abd-Elregal S., Abd Ellah N.H. Modulation of rifampicin-induced hepatotoxicity using poly (lactic-co-glycolic acid) nanoparticles: A study on rat and cell culture models. Nanomedicine. 2020;15:1375–1390. doi: 10.2217/nnm-2020-0001. PubMed DOI

Gondim B.L.C., Castellano L.R.C., de Castro R.D., Machado G., Carlo H.L., Valença A.M.G., de Carvalho F.G. Effect of chitosan nanoparticles on the inhibition of Candida spp. biofilm on denture base surface. Arch. Oral. Biol. 2018;94:99–107. doi: 10.1016/j.archoralbio.2018.07.004. PubMed DOI

Costa A.F., da Silva J.T., Martins J.A., Rocha V.L., de Menezes L.B., Amaral A.C. Chitosan nanoparticles encapsulating farnesol evaluated in vivo against Candida albicans. Braz. J. Microbiol. 2024;55:143–154. doi: 10.1007/s42770-023-01168-y. PubMed DOI PMC

Xu N., Gu J., Zhu Y., Wen H., Ren Q., Chen J. Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice. Int. J. Nanomed. 2011;6:905–913. doi: 10.2147/IJN.S17503. PubMed DOI PMC

Tang Y., Wu S., Lin J., Cheng L., Zhou J., Xie J., Huang K., Wang X., Yu Y., Chen Z., et al. Nanoparticles Targeted against Cryptococcal Pneumonia by Interactions between Chitosan and Its Peptide Ligand. Nano Lett. 2018;18:6207–6213. doi: 10.1021/acs.nanolett.8b02229. PubMed DOI

Panahi Y., Farshbaf M., Mohammadhosseini M., Mirahadi M., Khalilov R., Saghfi S., Akbarzadeh A. Recent advances on liposomal nanoparticles: Synthesis, characterization and biomedical applications. Artif. Cells Nanomed. Biotechnol. 2017;45:788–799. doi: 10.1080/21691401.2017.1282496. PubMed DOI

Bowden R., Chandrasekar P., White M.H., Li X., Pietrelli L., Gurwith M., van Burik J.A., Laverdiere M., Safrin S., Wingard J.R. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin. Infect. Dis. 2002;35:359–366. doi: 10.1086/341401. PubMed DOI

Olson J.A., Adler-Moore J.P., Jensen G.M., Schwartz J., Dignani M.C., Proffitt R.T. Comparison of the physicochemical, antifungal, and toxic properties of two liposomal amphotericin B products. Antimicrob. Agents Chemother. 2008;52:259–268. doi: 10.1128/AAC.00870-07. PubMed DOI PMC

Spellberg B., Ibrahim A.S., Chin-Hong P.V., Kontoyiannis D.P., Morris M.I., Perfect J.R., Fredricks D., Brass E.P. The Deferasirox–AmBisome Therapy for Mucormycosis (DEFEAT Mucor) study: A randomized, double-blinded, placebo-controlled trial. J. Antimicrob. Chemother. 2012;67:715–722. doi: 10.1093/jac/dkr375. PubMed DOI PMC

Lanternier F., Poiree S., Elie C., Garcia-Hermoso D., Bakouboula P., Sitbon K., Herbrecht R., Wolff M., Ribaud P., Lortholary O. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis. J. Antimicrob. Chemother. 2015;70:3116–3123. doi: 10.1093/jac/dkv236. PubMed DOI

Luo G., Gebremariam T., Lee H., French S.W., Wiederhold N.P., Patterson T.F., Filler S.G., Ibrahim A.S. Efficacy of liposomal amphotericin B and posaconazole in intratracheal models of murine mucormycosis. Antimicrob. Agents Chemother. 2013;57:3340–3347. doi: 10.1128/AAC.00313-13. PubMed DOI PMC

Cornely O.A., Maertens J., Bresnik M., Ebrahimi R., Ullmann A.J., Bouza E., Heussel C.P., Lortholary O., Rieger C., Boehme A. Liposomal amphotericin b as initial therapy for invasive mold infection: A randomized trial comparing a high–loading dose regimen with standard dosing (AmBiLoad Trial) Clin. Infect. Dis. 2007;44:1289–1297. doi: 10.1086/514341. PubMed DOI

Francis P., Lee J.W., Hoffman A., Peter J., Francesconi A., Bacher J., Shelhamer J., Pizzo P.A., Walsh T.J. Efficacy of unilamellar liposomal amphotericin B in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: The potential role of bronchoalveolar D-mannitol and serum galactomannan as markers of infection. J. Infect. Dis. 1994;169:356–368. doi: 10.1093/infdis/169.2.356. PubMed DOI

Clemons K., Stevens D. The contribution of animal models of aspergillosis to understanding pathogenesis, therapy and virulence. Med. Mycol. 2005;43:S101–S110. doi: 10.1080/13693780500051919. PubMed DOI

Arrieta A.C., Shea K., Dhar V., Cleary J.P., Kukreja S., Morris M., Vargas-Shiraishi O.M., Ashouri N., Singh J. Once-weekly liposomal amphotericin B as Candida prophylaxis in very low birth weight premature infants: A prospective, randomized, open-label, placebo-controlled pilot study. Clin. Ther. 2010;32:265–271. doi: 10.1016/j.clinthera.2010.02.016. PubMed DOI

Juster-Reicher A., Leibovitz E., Linder N., Amitay M., Flidel-Rimon O., Even-Tov S., Mogilner B., Barzilai A. Liposomal amphotericin B (AmBisome) in the treatment of neonatal candidiasis in very low birth weight infants. Infection. 2000;28:223–226. doi: 10.1007/s150100070040. PubMed DOI

Kuse E.-R., Chetchotisakd P., da Cunha C.A., Ruhnke M., Barrios C., Raghunadharao D., Sekhon J.S., Freire A., Ramasubramanian V., Demeyer I. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: A phase III randomised double-blind trial. Lancet. 2007;369:1519–1527. doi: 10.1016/S0140-6736(07)60605-9. PubMed DOI

Groll A.H., Giri N., Petraitis V., Petraitiene R., Candelario M., Bacher J.S., Piscitelli S.C., Walsh T.J. Comparative efficacy and distribution of lipid formulations of amphotericin B in experimental Candida albicans infection of the central nervous system. J. Infect. Dis. 2000;182:274–282. doi: 10.1086/315643. PubMed DOI

Leenders A.C., Reiss P., Portegies P., Clezy K., Hop W.C., Hoy J., Borleffs J.C., Allworth T., Kauffmann R.H., Jones P. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated Cryptococcal meningitis. Aids. 1997;11:1463–1471. doi: 10.1097/00002030-199712000-00010. PubMed DOI

Johnson P.C., Wheat L.J., Cloud G.A., Goldman M., Lancaster D., Bamberger D.M., Powderly W.G., Hafner R., Kauffman C.A., Dismukes W.E. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS. Ann. Intern. Med. 2002;137:105–109. doi: 10.7326/0003-4819-137-2-200207160-00008. PubMed DOI

Nucci F., Nouer S.A., Capone D., Anaissie E., Nucci M. Fusariosis. Semin. Respir. Crit. Care Med. 2015;36:706–714. doi: 10.1055/s-0035-1562897. PubMed DOI

Paosupap J., Basit A., Sajomsang W., Nalinbejapun S., Sripetthong S., Ovatlarnporn C. Evaluation of the antifungal properties of nanoliposomes containing rhinacanthin-C isolated from the leaves of Rhinacanthus nasutus. World J. Microbiol. Biotechnol. 2024;40:129. doi: 10.1007/s11274-024-03916-0. PubMed DOI