In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains
Abstract
:1. Introduction
2. Materials and Methods
2.1. Strains, DNA Extraction, and PCR Reaction
2.2. Antifungal Susceptibility Testing
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Ethical Approval
References
- Al-Hatmi, A.M.; Meis, J.F.; de Hoog, G.S. Fusarium: Molecular diversity and intrinsic drug resistance. PLoS Pathog. 2016, 12, e1005464. [Google Scholar] [CrossRef] [PubMed]
- Thomas, B.; Audonneau, N.C.; Machouart, M.; Debourgogne, A. Fusarium infections: Epidemiological aspects over 10 years in a university hospital in France. J. Infect. Public Health 2020, 13, 1089–1093. [Google Scholar] [CrossRef] [PubMed]
- Alastruey-Izquierdo, A.; Cuenca-Estrella, M.; Monzon, A.; Mellado, E.; Rodríguez-Tudela, J.L. Antifungal susceptibility profile of clinical Fusarium spp. isolates identified by molecular methods. J. Antimicrob. Chemother. 2008, 61, 805–809. [Google Scholar] [PubMed] [Green Version]
- Bansal, Y.; Singla, N.; Kaistha, N.; Sood, S.; Chander, J. Molecular identification of Fusarium species complex isolated from clinical samples and its antifungal susceptibility patterns. Curr. Med. Mycol. 2019, 5, 43. [Google Scholar] [CrossRef]
- Rampersad, S.N. Pathogenomics and management of Fusarium diseases in plants. Pathogens 2020, 9, 340. [Google Scholar] [CrossRef]
- Al-Hatmi, A.M.; de Hoog, G.S.; Meis, J.F. Multiresistant Fusarium pathogens on plants and humans: Solutions in (from) the antifungal pipeline? Infect. Drug Resist. 2019, 12, 3727. [Google Scholar]
- Antonissen, G.; Martel, A.; Pasmans, F.; Ducatelle, R.; Verbrugghe, E.; Vandenbroucke, V.; Li, S.; Haesebrouck, F.; Van Immerseel, F.; Croubels, S. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases. Toxins 2014, 6, 430–452. [Google Scholar] [CrossRef] [Green Version]
- Ji, F.; He, D.; Olaniran, A.O.; Mokoena, M.P.; Xu, J.; Shi, J. Occurrence, toxicity, production and detection of Fusarium mycotoxin: A review. Food Sci. Nutr. 2019, 1, 6. [Google Scholar] [CrossRef]
- Batista, B.G.; Chaves, M.A.D.; Reginatto, P.; Saraiva, O.J.; Fuentefria, A.M. Human fusariosis: An emerging infection that is difficult to treat. Rev. Soc. Bras. Med. Trop. 2020, 53, e20200013. [Google Scholar] [CrossRef]
- Al-Hatmi, A.M.; Bonifaz, A.; Ranque, S.; de Hoog, G.S.; Verweij, P.E.; Meis, J.F. Current antifungal treatment of fusariosis. Int. J. Antimicrob. Agents. 2018, 51, 326–332. [Google Scholar] [CrossRef] [Green Version]
- Abastabar, M.; Al-Hatmi, A.M.; Vafaei Moghaddam, M.; De Hoog, G.S.; Haghani, I.; Aghili, S.R.; Shokohi, T.; Hedayati, M.T.; Daie Ghazvini, R.; Kachuei, R.; et al. Potent activities of luliconazole, lanoconazole, and eight comparators against molecularly characterized Fusarium species. Antimicrob. Agents Chemother. 2018, 62, e00009-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tupaki-Sreepurna, A.; Thanneru, V.; Natarajan, S.; Sharma, S.; Gopi, A.; Sundaram, M.; Kindo, A.J. Phylogenetic diversity and in vitro susceptibility profiles of human pathogenic members of the Fusarium fujikuroi species complex isolated from South India. Mycopathologia 2018, 183, 529–540. [Google Scholar] [CrossRef] [PubMed]
- Taj-Aldeen, S.J. Reduced multidrug susceptibility profile is a common feature of opportunistic Fusarium species: Fusarium multi-drug resistant pattern. J. Fungi. 2017, 3, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Góralska, K.; Błaszkowska, J.; Dzikowiec, M. The occurrence of potentially pathogenic filamentous fungi in recreational surface water as a public health risk. J. Water Health 2020, 18, 127–144. [Google Scholar] [CrossRef] [PubMed]
- Aquino, V.R.; Verçosa, E.B.; Falhauber, G.; Lunardi, L.W.; Silla, L.; Pasqualotto, A.C. Distribution of filamentous fungi causing invasive fungal disease at the Haematological Unit, Hospital de Clinicas de Porto Alegre, Brazil. Braz. J. Infect. Dis. 2010, 14, 277–280. [Google Scholar] [CrossRef] [Green Version]
- Najafzadeh, M.J.; Dolatabadi, S.; de Hoog, S.; Esfahani, M.K.; Haghani, I.; Aghili, S.R.; Ghazvini, R.D.; Rezaei-Matehkolaei, A.; Abastabar, M.; Al-Hatmi, A. Phylogenetic analysis of clinically relevant Fusarium species in Iran. Mycopathologia 2020, 185, 515–525. [Google Scholar] [CrossRef]
- Herkert, P.F.; Al-Hatmi, A.; de Oliveira Salvador, G.L.; Muro, M.D.; Pinheiro, R.L.; Nucci, M.; Queiroz-Telles, F.; de Hoog, G.S.; Meis, J.F. Molecular characterization and antifungal susceptibility of clinical Fusarium species from Brazil. Front. Microbiol. 2020, 10, 737. [Google Scholar] [CrossRef] [Green Version]
- Gaviria-Rivera, A.; Giraldo-López, A.; Santa-Cardona, C.; Cano-Restrepo, L. Molecular identification of clinical isolates of Fusarium in Colombia. Rev. Salud Publica 2018, 20, 94–102. [Google Scholar] [CrossRef]
- Al-Hatmi, A.; Curfs-Breuker, I.; De Hoog, G.S.; Meis, J.F.; Verweij, P.E. Antifungal susceptibility testing of Fusarium: A practical approach. J. Fungi 2017, 3, 19. [Google Scholar] [CrossRef] [Green Version]
- Rossato, L.; Camargo dos Santos, M.; Vitale, R.G.; de Hoog, S.; Ishida, K. Alternative treatment of fungal infections: Synergy with non-antifungal agents. Mycoses 2021, 64, 232–244. [Google Scholar] [CrossRef]
- Dorlo, T.P.; Balasegaram, M.; Beijnen, J.H.; de Vries, P.J. Miltefosine: A review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. Antimicrob. Agents Chemother. 2012, 67, 2576–2597. [Google Scholar] [CrossRef] [PubMed]
- Vila, T.; Ishida, K.; Seabra, S.H.; Rozental, S. Miltefosine inhibits Candida albicans and non-albicans Candida spp. biofilms and impairs the dispersion of infectious cells. Int. J. Antimicrob. Agents 2016, 48, 512–520. [Google Scholar] [CrossRef]
- Imbert, S.; Palous, M.; Meyer, I.; Dannaoui, E.; Mazier, D.; Datry, A.; Fekkar, A. In vitro combination of voriconazole and miltefosine against clinically relevant molds. Antimicrob. Agents Chemother. 2014, 58, 6996–6998. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rossi, D.C.P.; de Castro Spadari, C.; Nosanchuk, J.D.; Taborda, C.P.; Ishida, K. Miltefosine is fungicidal to Paracoccidioides spp. yeast cells but subinhibitory concentrations induce melanisation. Int. J. Antimicrob. Agents 2017, 49, 465–471. [Google Scholar] [CrossRef] [PubMed]
- Biswas, C.; Sorrell, T.C.; Djordjevic, J.T.; Zuo, X.; Jolliffe, K.A.; Chen, S.C.A. In Vitro activity of miltefosine as a single agent and in combination with voriconazole or posaconazole against uncommon filamentous fungal pathogens. Antimicrob. Chemother. 2013, 68, 2842–2846. [Google Scholar] [CrossRef] [PubMed]
- Vila, T.V.M.; Quintanilha, N.S.; Rozental, S. Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro. J. Med. Microbiol. 2015, 64, 1436–1449. [Google Scholar] [CrossRef] [PubMed]
- Rollin-Pinheiro, R.; Almeida, Y.D.C.; Rochetti, V.P.; Xisto, M.I.D.D.S.; Borba-Santos, L.P.; Rozental, S.; Barreto-Bergter, E. Miltefosine against Scedosporium and Lomentospora species: Antifungal activity and its effects on fungal cells. Front. Cell. Infect. Microbiol. 2021, 11, 698662. [Google Scholar] [CrossRef]
- Al Hatmi, A.M.S. Phylogeny, Diagnostics and Antifungal Susceptibility of Clinically Relevant Fusarium Species; Universiteit van Amsterdam: Amsterdam, The Netherlands, 2016. [Google Scholar]
- CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi, 3rd ed.; CLSI standard M38; Clinical and Laboratory Standards Institute: Wayne, PA, USA, 2017. [Google Scholar]
- Al-Hatmi, A.M.; Meletiadis, J.; Curfs-Breuker, I.; Bonifaz, A.; Meis, J.F.; De Hoog, G.S. In vitro combinations of natamycin with voriconazole, itraconazole and micafungin against clinical Fusarium strains causing keratitis. Antimicrob. Chemother. 2016, 71, 953–955. [Google Scholar] [CrossRef] [Green Version]
- Al-Hatmi, A.M.; van Diepeningen, A.D.; Curfs-Breuker, I.; de Hoog, G.S.; Meis, J.F. Specific antifungal susceptibility profiles of opportunists in the Fusarium fujikuroi complex. Antimicrob. Chemother. 2015, 70, 1068–1071. [Google Scholar] [CrossRef] [Green Version]
- Vagace, J.M.; Sanz-Rodriguez, C.; Casado, M.S.; Alonso, N.; Garcia-Dominguez, M.; de la Llana, F.G.; Zarallo, L.; Fajardo, M.; Bajo, R. Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: A case report. BMC Infect. Dis. 2007, 7, 40. [Google Scholar] [CrossRef] [Green Version]
- Apostolidis, J.; Bouzani, M.; Platsouka, E.; Belasiotou, H.; Stamouli, M.; Harhalakis, N.; Boutati, E.I.; Paniara, O.; Nikiforakis, E. Resolution of fungemia due to Fusarium species in a patient with acute leukemia treated with caspofungin. Clin. Infect. Dis. 2003, 36, 1349–1350. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stempel, J.M.; Hammond, S.P.; Sutton, D.A.; Weiser, L.M.; Marty, F.M. Invasive fusariosis in the voriconazole era: Single-center 13-year experience. In Open Forum Infectious Diseases; Oxford University Press: Oxford, UK, 2015; Volume 2, p. 3. [Google Scholar]
- Rosa, P.D.; Heidrich, D.; Corrêa, C.; Scroferneker, M.L.; Vettorato, G.; Fuentefria, A.M.; Goldani, L.Z. Genetic diversity and antifungal susceptibility of Fusarium isolates in onychomycosis. Mycoses 2017, 60, 616–622. [Google Scholar] [CrossRef] [PubMed]
- Gupta, C.; Jongman, M.; Das, S.; Snehaa, K.; Bhattacharya, S.N.; Seyedmousavi, S.; van Diepeningen, A.D. Genotyping and in vitro antifungal susceptibility testing of Fusarium isolates from onychomycosis in India. Mycopathologia 2016, 181, 497–504. [Google Scholar] [CrossRef] [PubMed]
- Oliveira dos Santos, C.; Kolwijck, E.; van der Lee, H.A.; Tehupeiory-Kooreman, M.C.; Al-Hatmi, A.M.; Matayan, E.; Burton, M.J.; Eggink, C.A.; Verweij, P.E. In vitro activity of chlorhexidine compared with seven antifungal agents against 98 Fusarium isolates recovered from fungal keratitis patients. Antimicrob. Chemother. 2019, 63, e02669-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blaize, M.; Normand, A.C.; Imbert, S.; Al-Hatmi, A.M.; Chryssanthou, E.; Cassaing, S.; Schuttler, C.; Hasseine, L.; Mahinc, C.; Costa, D.; et al. Antifungal Susceptibility of 182 Fusarium Species Isolates from 20 European Centers: Comparison between EUCAST and Gradient Concentration Strip Methods. Antimicrob. Chemother. 2021, 65, e01495-21. [Google Scholar] [CrossRef]
- Spadari, C.D.C.; Vila, T.; Rozental, S.; Ishida, K. Miltefosine has a postantifungal effect and induces apoptosis in Cryptococcus yeasts. Antimicrob. Chemother. 2018, 62, e00312-18. [Google Scholar] [CrossRef] [Green Version]
- Borba-Santos, L.P.; Gagini, T.; Ishida, K.; de Souza, W.; Rozental, S. Miltefosine is active against Sporothrix brasiliensis isolates with in vitro low susceptibility to amphotericin B or itraconazole. J. Med. Microbiol. 2015, 64, 415–422. [Google Scholar] [CrossRef] [Green Version]
- Vila, T.V.; Ishida, K.; de Souza, W.; Prousis, K.; Calogeropoulou, T.; Rozental, S. Effect of alkylphospholipids on Candida albicans biofilm formation and maturation. J. Antimicrob. Chemother. 2013, 68, 113–125. [Google Scholar] [CrossRef] [Green Version]
- Tong, Z.; Widmer, F.; Sorrell, T.C.; Guse, Z.; Jolliffe, K.A.; Halliday, C.; Lee, O.C.; Kong, F.; Wright, L.C.; Chen, S.C. In vitro activities of miltefosine and two novel antifungal biscationic salts against a panel of 77 dermatophytes. Antimicrob. Agents Chemother. 2007, 51, 2219–2222. [Google Scholar] [CrossRef] [Green Version]
- Widmer, F.; Wright, L.C.; Obando, D.; Handke, R.; Ganendren, R.; Ellis, D.H.; Sorrell, T.C. Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis. Antimicrob. Agents Chemother. 2006, 50, 414–421. [Google Scholar] [CrossRef] [Green Version]
- Seifert, K.; Simon, L.C. In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrob. Agents Chemother. 2006, 50, 73–79. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wiederhold, N.P.; Najvar, L.K.; Bocanegra, R.; Kirkpatrick, W.R.; Sorrell, T.C.; Patterson, T.F. Limited activity of miltefosine in murine models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Antimicrob. Agents Chemother. 2013, 57, 745–750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoenigl, M.; Salmanton-García, J.; Walsh, T.J.; Nucci, M.; Neoh, C.F.; Jenks, J.D.; Lackner, M.; Sprute, R.; Al-Hatmi, A.M.S.; Bassetti, M.; et al. Global guideline for the diagnosis and management of rare mould infections: An initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology. Lancet Infect Dis. 2021, 21, e246–e257, Erratum in Lancet Infect Dis. 2021, 21, e81. [Google Scholar] [CrossRef] [PubMed]
Source and Antifungal Agent | MIC/MEC50 | MIC/MEC90 | MIC/MEC Range | GM | Mode |
---|---|---|---|---|---|
All Fusarium isolates (n = 110) | (μg/mL) | ||||
Miltefosine | 2 | 2 | 0.25–4 | 1.44 | 2 |
Voriconazole | 2 | 8 | 0.125–16 | 2.15 | 4 |
Amphotericin B | 1 | 2 | 0.032–4 | 0.8 | 1 |
Itraconazole | 16 | 16 | 2–16 | 14.19 | 16 |
Caspofungin | 8 | 8 | 0.125–8 | 7.18 | 8 |
Fusarium, clinical (n = 68) | |||||
Miltefosine | 2 | 2 | 0.25–4 | 1.50 | 2 |
Voriconazole | 4 | 8 | 0.25–16 | 2.91 | 4 |
Amphotericin B | 1 | 2 | 0.125–4 | 0.74 | 1 |
Itraconazole | 16 | 16 | 2–16 | 14.89 | 16 |
Caspofungin | 8 | 8 | 2–8 | 7.29 | 8 |
Fusarium, environmental (n = 42) | |||||
Miltefosine | 1 | 2 | 0.5–4 | 1.34 | 1 |
Voriconazole | 2 | 4 | 0.125–8 | 1.32 | 1 |
Amphotericin B | 1 | 4 | 0.032–4 | 0.92 | 1 |
Itraconazole | 16 | 16 | 2–16 | 13.12 | 16 |
Caspofungin | 8 | 8 | 0.125–8 | 7.01 | 8 |
Clinical F. fujikuroi complex (n =25) | |||||
Miltefosine | 2 | 2 | 0.25–4 | 1.51 | 2 |
Voriconazole | 2 | 4 | 0.5–8 | 2.42 | 4 |
Amphotericin B | 1 | 2 | 0.125–4 | 1.02 | 1 |
Itraconazole | 16 | 16 | 8–16 | 15.13 | 16 |
Caspofungin | 8 | 8 | 4–8 | 7.78 | 8 |
Environmental F. fujikuroi complex (n = 38) | |||||
Miltefosine | 1 | 2 | 0.5–4 | 1.29 | 1 |
Voriconazole | 2 | 4 | 0.125–8 | 1.33 | 1 |
Amphotericin B | 1 | 4 | 0.032–4 | 0.91 | 1 |
Itraconazole | 16 | 16 | 2–16 | 13.09 | 16 |
Caspofungin | 8 | 8 | 0.125–8 | 6.91 | 8 |
Clinical F. solani complex (n = 36) | |||||
Miltefosine | 2 | 2 | 1–2 | 1.46 | 2 |
Voriconazole | 4 | 8 | 0.25–16 | 3.17 | 8 |
Amphotericin B | 0.5 | 2 | 0.125–4 | 0.6 | 1 |
Itraconazole | 16 | 16 | 8–16 | 15.39 | 16 |
Caspofungin | 8 | 8 | 2–8 | 7.12 | 8 |
Clinical F. oxysporum complex (n = 5) | |||||
Miltefosine | - | - | 1–2 | 1.74 | 2 |
Voriconazole | - | - | 2–16 | 5.27 | 4 |
Amphotericin B | - | - | 0.25–4 | 0.75 | 0.5 |
Itraconazole | - | - | 16 | 16 | 16 |
Caspofungin | - | - | 8 | 8 | 8 |
Clinical F. incarnatum equiseti species complex (n = 1) | |||||
Miltefosine | 2 | ||||
Voriconazole | 1 | ||||
Amphotericin B | 0.25 | ||||
Itraconazole | 16 | ||||
Caspofungin | 2 | ||||
Environmental F. incarnatum equiseti species complex (n = 2) | |||||
Miltefosine | 1–4 | ||||
Voriconazole | 0.5–1 | ||||
Amphotericin B | 0.5–1 | ||||
Itraconazole | 8–16 | ||||
Caspofungin | 8 | ||||
Clinical F. lateritium complex (n = 1) | |||||
Miltefosine | 1 | ||||
Voriconazole | 2 | ||||
Amphotericin B | 1 | ||||
Itraconazole | 2 | ||||
Caspofungin | 8 | ||||
Environmental F. graminearum complex (n = 1) | |||||
Miltefosine | 2 | ||||
Voriconazole | 2 | ||||
Amphotericin B | 4 | ||||
Itraconazole | 16 | ||||
Caspofungin | 8 | ||||
Environmental Fusarium redolens species complex (n = 1) | |||||
Miltefosine | 2 | ||||
Voriconazole | 2 | ||||
Amphotericin B | 0.5 | ||||
Itraconazole | 16 | ||||
Caspofungin | 8 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Nosratabadi, M.; Akhtari, J.; Faeli, L.; Haghani, I.; Aghili, S.R.; Shokohi, T.; Hedayati, M.T.; Zarrinfar, H.; Mohammadi, R.; Najafzadeh, M.J.; et al. In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains. J. Fungi 2022, 8, 709. https://doi.org/10.3390/jof8070709
Nosratabadi M, Akhtari J, Faeli L, Haghani I, Aghili SR, Shokohi T, Hedayati MT, Zarrinfar H, Mohammadi R, Najafzadeh MJ, et al. In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains. Journal of Fungi. 2022; 8(7):709. https://doi.org/10.3390/jof8070709
Chicago/Turabian StyleNosratabadi, Mohsen, Javad Akhtari, Leila Faeli, Iman Haghani, Seyed Reza Aghili, Tahereh Shokohi, Mohammad Taghi Hedayati, Hossein Zarrinfar, Rasoul Mohammadi, Mohammad Javad Najafzadeh, and et al. 2022. "In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains" Journal of Fungi 8, no. 7: 709. https://doi.org/10.3390/jof8070709
APA StyleNosratabadi, M., Akhtari, J., Faeli, L., Haghani, I., Aghili, S. R., Shokohi, T., Hedayati, M. T., Zarrinfar, H., Mohammadi, R., Najafzadeh, M. J., Khodavaisy, S., Al-Harrasi, A., Javan-Nikkhah, M., Kachuei, R., Salimi, M., Fattahi, M., Badali, H., Al Hatmi, A. M. S., & Abastabar, M. (2022). In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains. Journal of Fungi, 8(7), 709. https://doi.org/10.3390/jof8070709