New and Promising Chemotherapeutics for Emerging Infections Involving Drug-resistant Non-albicans Candida Species

Laura    Nunes    Silva; Thaís    Pereira    de Mello; Lívia       de Souza Ramos; Marta    Helena    Branquinha; André     Luis Souza   dos Santos
Abstract

Fungal infections are a veritable public health problem worldwide. The increasing number of patient populations at risk (e.g. transplanted individuals, cancer patients, and HIV-infected people), as well as the use of antifungal agents for prophylaxis in medicine, have favored the emergence of previously rare or newly identified fungal species. Indeed, novel antifungal resistance patterns have been observed, including environmental sources and the emergence of simultaneous resistance to different antifungal classes, especially in Candida spp., which are known for the multidrug-resistance (MDR) profile. In order to circumvent this alarming scenario, the international researchers’ community is engaged in discovering new, potent, and promising compounds to be used in a near future to treat resistant fungal infections in hospital settings on a global scale. In this context, many compounds with antifungal action from both natural and synthetic sources are currently under clinical development, including those that target either ergosterol or β(1,3)-D-glucan, presenting clear evidence of pharmacologic/pharmacokinetic advantages over currently available drugs against these two well-known fungal target structures. Among these are the tetrazoles VT-1129, VT-1161, and VT-1598, the echinocandin CD101, and the glucan synthase inhibitor SCY-078. In this review, we compiled the most recent antifungal compounds that are currently in clinical trials of development and described the potential outcomes against emerging and rare Candida species, with a focus on C. auris, C. dubliniensis, C. glabrata, C. guilliermondii, C. haemulonii, and C. rugosa. In addition to possibly overcoming the limitations of currently available antifungals, new investigational chemical agents that can enhance the classic antifungal activity, thereby reversing previously resistant phenotypes, were also highlighted. While novel and increasingly MDR non-albicans Candida species continue to emerge worldwide, novel strategies for rapid identification and treatment are needed to combat these life-threatening opportunistic fungal infections.
Keywords: Non-albicans Candida species, Invasive fungal infections, Azoles, Echinocandins, Antifungal resistance, Promising compounds.
« Previous Next »
Graphical Abstract

[1] 
Vallabhaneni, S.; Mody, R.K.; Walker, T.; Chiller, T. The global burden of fungal diseases. Infect. Dis. Clin. North Am.,  2016, 30(1), 1-11.
[http://dx.doi.org/10.1016/j.idc.2015.10.004] [PMID:  26739604] 
[2] 
Brown, G.D.; Denning, D.W.; Gow, N.A.R.; Levitz, S.M.; Netea, M.G.; White, T.C. Hidden killers: human fungal infections. Sci. Transl. Med.,  2012, 4(165)165rv13
[http://dx.doi.org/10.1126/scitranslmed.3004404] [PMID:  23253612] 
[3] 
Kriengkauykiat, J.; Ito, J.I.; Dadwal, S.S. Epidemiology and treatment approaches in management of invasive fungal infections. Clin. Epidemiol.,  2011, 3, 175-191.
[4] 
Brown, G.D.; Meintjes, G.; Kolls, J.K.; Gray, C.; Horsnell, W.; Achan, B.; Alber, G.; Aloisi, M.; Armstrong-James, D.; Beale, M.; Bicanic, T.; Black, J.; Bohjanen, P.; Botes, A.; Boulware, D.R.; Brown, G.; Bunjun, R.; Carr, W.; Casadevall, A.; Chang, C.; Chivero, E.; Corcoran, C.; Cross, A.; Dawood, H.; Day, J.; De Bernardis, F.; De Jager, V.; De Repentigny, L.; Denning, D.; Eschke, M.; Finkelman, M.; Govender, N.; Gow, N.; Graham, L.; Gryschek, R.; Hammond-Aryee, K.; Harrison, T.; Heard, N.; Hill, M.; Hoving, J.C.; Janoff, E.; Jarvis, J.; Kayuni, S.; King, K.; Kolls, J.; Kullberg, B.J.; Lalloo, D.G.; Letang, E.; Levitz, S.; Limper, A.; Longley, N.; Machiridza, T.R.; Mahabeer, Y.; Martinsons, N.; Meiring, S.; Meya, D.; Miller, R.; Molloy, S.; Morris, L.; Mukaremera, L.; Musubire, A.K.; Muzoora, C.; Nair, A.; Nakiwala Kimbowa, J.; Netea, M.; Nielsen, K.; O’hern, J.; Okurut, S.; Parker, A.; Patterson, T.; Pennap, G.; Perfect, J.; Prinsloo, C.; Rhein, J.; Rolfes, M.A.; Samuel, C.; Schutz, C.; Scriven, J.; Sebolai, O.M.; Sojane, K.; Sriruttan, C.; Stead, D.; Steyn, A.; Thawer, N.K.; Thienemann, F.; Von Hohenberg, M.; Vreulink, J.M.; Wessels, J.; Wood, K.; Yang, Y.L. AIDS-related mycoses: The way forward. Trends Microbiol.,  2014, 22(3), 107-109.
[http://dx.doi.org/10.1016/j.tim.2013.12.008] [PMID:  24581941] 
[5] 
Nucci, M.; Marr, K.A. Emerging fungal diseases. Clin. Infect. Dis.,  2005, 41(4), 521-526.
[http://dx.doi.org/10.1086/432060] [PMID:  16028162] 
[6] 
Enoch, D.A.; Yang, H.; Aliyu, S.H.; Micallef, C. The changing epidemiology of invasive fungal infections. Methods Mol. Biol.,  2017, 1508, 17-65.
[http://dx.doi.org/10.1007/978-1-4939-6515-1_2] 
[7] 
Pfaller, M.A.; Diekema, D.J.; Gibbs, D.L.; Newell, V.A.; Ellis, D.; Tullio, V.; Rodloff, A.; Fu, W.; Ling, T.A. Results from the ARTEMIS DISK global antifungal surveillance study, 1997 to 2007: A 10.5-year analysis of susceptibilities of Candida Species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J. Clin. Microbiol.,  2010, 48(4), 1366-1377.
[http://dx.doi.org/10.1128/JCM.02117-09] [PMID:  20164282] 
[8] 
Pfaller, M.A.; Jones, R.N.; Castanheira, M. Regional data analysis of Candida non-albicans strains collected in United States medical sites over a 6-year period, 2006-2011. Mycoses,  2014, 57(10), 602-611.
[http://dx.doi.org/10.1111/myc.12206] [PMID:  24863164] 
[9] 
Lockhart, S.R.; Iqbal, N.; Cleveland, A.A.; Farley, M.M.; Harrison, L.H.; Bolden, C.B.; Baughman, W.; Stein, B.; Hollick, R.; Park, B.J.; Chiller, T. Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011. J. Clin. Microbiol.,  2012, 50(11), 3435-3442.
[http://dx.doi.org/10.1128/JCM.01283-12] [PMID:  22875889] 
[10] 
Matsumoto, E.; Boyken, L.; Tendolkar, S.; McDanel, J.; Castanheira, M.; Pfaller, M.; Diekema, D. Candidemia surveillance in Iowa: emergence of echinocandin resistance. Diagn. Microbiol. Infect. Dis.,  2014, 79(2), 205-208.
[http://dx.doi.org/10.1016/j.diagmicrobio.2014.02.016] [PMID:  24666704] 
[11] 
Cleveland, A.A.; Harrison, L.H.; Farley, M.M.; Hollick, R.; Stein, B.; Chiller, T.M.; Lockhart, S.R.; Park, B.J. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008-2013: results from population-based surveillance. PLoS One,  2015, 10(3)e0120452
[http://dx.doi.org/10.1371/journal.pone.0120452] [PMID:  25822249] 
[12] 
Sandven, P.; Bevanger, L.; Digranes, A.; Haukland, H.H.; Mannsåker, T.; Gaustad, P. Candidemia in Norway (1991 to 2003): results from a nationwide study. J. Clin. Microbiol.,  2006, 44(6), 1977-1981.
[http://dx.doi.org/10.1128/JCM.00029-06] [PMID:  16757587] 
[13] 
Asmundsdóttir, L.R.; Erlendsdóttir, H.; Gottfredsson, M. Increasing incidence of candidemia: results from a 20-year nationwide study in Iceland. J. Clin. Microbiol.,  2002, 40(9), 3489-3492.
[http://dx.doi.org/10.1128/JCM.40.9.3489-3492.2002] [PMID:  12202600] 
[14] 
Poikonen, E.; Lyytikäinen, O.; Anttila, V-J.; Ruutu, P. Candidemia in Finland, 1995-1999. Emerg. Infect. Dis.,  2003, 9(8), 985-990.
[http://dx.doi.org/10.3201/eid0908.030069] [PMID:  12967498] 
[15] 
Arendrup, M.C.; Fuursted, K.; Gahrn-Hansen, B.; Jensen, I.M.; Knudsen, J.D.; Lundgren, B.; Schønheyder, H.C.; Tvede, M. Seminational surveillance of fungemia in Denmark: notably high rates of fungemia and numbers of isolates with reduced azole susceptibility. J. Clin. Microbiol.,  2005, 43(9), 4434-4440.
[http://dx.doi.org/10.1128/JCM.43.9.4434-4440.2005] [PMID:  16145088] 
[16] 
Das, I.; Nightingale, P.; Patel, M.; Jumaa, P. Epidemiology, clinical characteristics, and outcome of candidemia: experience in a tertiary referral center in the UK. Int. J. Infect. Dis.,  2011, 15(11), e759-e763.
[http://dx.doi.org/10.1016/j.ijid.2011.06.006] [PMID:  21840742] 
[17] 
Trouvé, C.; Blot, S.; Hayette, M.P.; Jonckheere, S.; Patteet, S.; Rodriguez-Villalobos, H.; Symoens, F.; Van Wijngaerden, E.; Lagrou, K. Epidemiology and reporting of candidaemia in Belgium: a multi-centre study. Eur. J. Clin. Microbiol. Infect. Dis.,  2017, 36(4), 649-655.
[http://dx.doi.org/10.1007/s10096-016-2841-3] [PMID:  27858242] 
[18] 
Chapman, B.; Slavin, M.; Marriott, D.; Halliday, C.; Kidd, S.; Arthur, I.; Bak, N.; Heath, C.H.; Kennedy, K.; Morrissey, C.O.; Sorrell, T.C.; van Hal, S.; Keighley, C.; Goeman, E.; Underwood, N.; Hajkowicz, K.; Hofmeyr, A.; Leung, M.; Macesic, N.; Botes, J.; Blyth, C.; Cooley, L.; George, C.R.; Kalukottege, P.; Kesson, A.; McMullan, B.; Baird, R.; Robson, J.; Korman, T.M.; Pendle, S.; Weeks, K.; Liu, E.; Cheong, E.; Chen, S. Changing epidemiology of candidaemia in Australia. J. Antimicrob. Chemother.,  2017, 72(4), 1103-1108.
[http://dx.doi.org/10.1093/jac/dkx047] [PMID:  28364558] 
[19] 
Nucci, M.; Queiroz-Telles, F.; Alvarado-Matute, T.; Tiraboschi, I.N.; Cortes, J.; Zurita, J.; Guzman-Blanco, M.; Santolaya, M.E.; Thompson, L.; Sifuentes-Osornio, J.; Echevarria, J.I.; Colombo, A.L. Epidemiology of candidemia in Latin America: a laboratory-based survey. PLoS One,  2013, 8(3)e59373
[http://dx.doi.org/10.1371/journal.pone.0059373] [PMID:  23527176] 
[20] 
Colombo, A.L.; Nucci, M.; Park, B.J.; Nouér, S.A.; Arthington-Skaggs, B.; da Matta, D.A.; Warnock, D.; Morgan, J. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J. Clin. Microbiol.,  2006, 44(8), 2816-2823.
[http://dx.doi.org/10.1128/JCM.00773-06] [PMID:  16891497] 
[21] 
Doi, A.M.; Pignatari, A.C.; Edmond, M.B.; Marra, A.R.; Camargo, L.F.; Siqueira, R.A.; da Mota, V.P.; Colombo, A.L. Epidemiology and microbiologic characterization of nosocomial candidemia from a Brazilian National Surveillance Program. PLoS One,  2016, 11(1)e0146909
[http://dx.doi.org/10.1371/journal.pone.0146909] [PMID:  26808778] 
[22] 
Govender, N.P.; Patel, J.; Magobo, R.E.; Naicker, S.; Wadula, J.; Whitelaw, A.; Coovadia, Y.; Kularatne, R.; Govind, C.; Lockhart, S.R.; Zietsman, I.L. Emergence of azole-resistant Candida parapsilosis causing bloodstream infection: results from laboratory-based sentinel surveillance in South Africa. J. Antimicrob. Chemother.,  2016, 71(7), 1994-2004.
[http://dx.doi.org/10.1093/jac/dkw091] [PMID:  27125552] 
[23] 
Tan, T.Y.; Hsu, L.Y.; Alejandria, M.M.; Chaiwarith, R.; Chinniah, T.; Chayakulkeeree, M.; Choudhury, S.; Chen, Y.H.; Shin, J.H.; Kiratisin, P.; Mendoza, M.; Prabhu, K.; Supparatpinyo, K.; Tan, A.L.; Phan, X.T.; Tran, T.T.; Nguyen, G.B.; Doan, M.P.; Huynh, V.A.; Nguyen, S.M.; Tran, T.B.; Van Pham, H. Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia-Pacific region. Med. Mycol.,  2016, 54(5), 471-477.
[http://dx.doi.org/10.1093/mmy/myv114] [PMID:  26868904] 
[24] 
Tan, B.H.; Chakrabarti, A.; Li, R.Y.; Patel, A.K.; Watcharananan, S.P.; Liu, Z.; Chindamporn, A.; Tan, A.L.; Sun, P.L.; Wu, U.I.; Chen, Y.C. Incidence and species distribution of candidaemia in Asia: a laboratory-based surveillance study. Clin. Microbiol. Infect.,  2015, 21(10), 946-953.
[http://dx.doi.org/10.1016/j.cmi.2015.06.010] [PMID:  26100373] 
[25] 
Wang, H.; Xu, Y-C.; Hsueh, P-R. Epidemiology of candidemia and antifungal susceptibility in invasive Candida species in the Asia-Pacific region. Future Microbiol.,  2016, 11(11), 1461-1477.
[http://dx.doi.org/10.2217/fmb-2016-0099] [PMID:  27750452] 
[26] 
Lin, S.; Chen, R.; Zhu, S.; Wang, H.; Wang, L.; Zou, J.; Yan, J.; Zhang, X.; Farmakiotis, D.; Tan, X.; Mylonakis, E. Candidemia in adults at a tertiary hospital in China: clinical characteristics, species distribution, resistance, and outcomes. Mycopathologia,  2018, 183(4), 679-689.
[http://dx.doi.org/10.1007/s11046-018-0258-5] [PMID:  29572768] 
[27] 
Puig-Asensio, M.; Padilla, B.; Garnacho-Montero, J.; Zaragoza, O.; Aguado, J.M.; Zaragoza, R.; Montejo, M.; Muñoz, P.; Ruiz-Camps, I.; Cuenca-Estrella, M.; Almirante, B. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin. Microbiol. Infect.,  2014, 20(4), 245-254.
[http://dx.doi.org/10.1111/1469-0691.12380] [PMID:  24125548] 
[28] 
Bassetti, M.; Merelli, M.; Righi, E.; Diaz-Martin, A.; Rosello, E.M.; Luzzati, R.; Parra, A.; Trecarichi, E.M.; Sanguinetti, M.; Posteraro, B.; Garnacho-Montero, J.; Sartor, A.; Rello, J.; Tumbarello, M. Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain. J. Clin. Microbiol.,  2013, 51(12), 4167-4172.
[http://dx.doi.org/10.1128/JCM.01998-13] [PMID:  24108614] 
[29] 
Kreusch, A.; Karstaedt, A.S. Candidemia among adults in Soweto, South Africa, 1990-2007. Int. J. Infect. Dis.,  2013, 17(8), e621-e623.
[http://dx.doi.org/10.1016/j.ijid.2013.02.010] [PMID:  23535300] 
[30] 
Chakrabarti, A.; Sood, P.; Rudramurthy, S.M.; Chen, S.; Kaur, H.; Capoor, M.; Chhina, D.; Rao, R.; Eshwara, V.K.; Xess, I.; Kindo, A.J.; Umabala, P.; Savio, J.; Patel, A.; Ray, U.; Mohan, S.; Iyer, R.; Chander, J.; Arora, A.; Sardana, R.; Roy, I.; Appalaraju, B.; Sharma, A.; Shetty, A.; Khanna, N.; Marak, R.; Biswas, S.; Das, S.; Harish, B.N.; Joshi, S.; Mendiratta, D. Incidence, characteristics and outcome of ICU-acquired candidemia in India. Intensive Care Med.,  2015, 41(2), 285-295.
[http://dx.doi.org/10.1007/s00134-014-3603-2] [PMID:  25510301] 
[31] 
Braga, P.R.; Cruz, I.L.; Ortiz, I.; Barreiros, G.; Nouér, S.A.; Nucci, M. Secular trends of candidemia at a Brazilian tertiary care teaching hospital. Braz. J. Infect. Dis.,  2018, 22, 273-277.
[http://dx.doi.org/10.1016/j.bjid.2018.07.008] 
[32] 
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.; Berkow, E.L.; Castanheira, M.; Magobo, R.E.; Jabeen, K.; Asghar, R.J.; Meis, J.F.; Jackson, B.; Chiller, T.; Litvintseva, A.P. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin. Infect. Dis.,  2017, 64(2), 134-140.
[http://dx.doi.org/10.1093/cid/ciw691] [PMID:  27988485] 
[33] 
Alcoba-Flórez, J.; Méndez-Alvarez, S.; Cano, J.; Guarro, J.; Pérez-Roth, E.; del Pilar Arévalo, M. Phenotypic and molecular characterization of Candida nivariensis sp. nov., a possible new opportunistic fungus. J. Clin. Microbiol.,  2005, 43(8), 4107-4111.
[http://dx.doi.org/10.1128/JCM.43.8.4107-4111.2005] [PMID:  16081957] 
[34] 
Correia, A.; Sampaio, P.; James, S.; Pais, C. Candida bracarensis sp. nov., a novel anamorphic yeast species phenotypically similar to Candida glabrata. Int. J. Syst. Evol. Microbiol.,  2006, 56(Pt 1), 313-317.
[http://dx.doi.org/10.1099/ijs.0.64076-0] [PMID:  16403904] 
[35] 
Morales-López, S.E.; Taverna, C.G.; Bosco-Borgeat, M.E.; Maldonado, I.; Vivot, W.; Szusz, W.; Garcia-Effron, G.; Córdoba, S.B. Candida glabrata species complex prevalence and antifungal susceptibility testing in a culture collection: First description of Candida nivariensis in Argentina. Mycopathologia,  2016, 181(11-12), 871-878.
[http://dx.doi.org/10.1007/s11046-016-0052-1] [PMID:  27681573] 
[36] 
Glöckner, A.; Cornely, O.A. Candida glabrata--unique features and challenges in the clinical management of invasive infections. Mycoses,  2015, 58(8), 445-450.
[http://dx.doi.org/10.1111/myc.12348] [PMID:  26207423] 
[37] 
Essig, F.; Hunniger, K.; Dietrich, S.; Figge, M.T.; Kurzai, O. Human neutrophils dump Candida glabrata after intracellular killing. Fungal Genet. Biol.,  2015, 84, 37-40.
[http://dx.doi.org/10.1016/j.fgb.2015.09.008] 
[38] 
Kasper, L.; Seider, K.; Hube, B. Intracellular survival of Candida glabrata in macrophages: immune evasion and persistence. FEMS Yeast Res.,  2015, 15(5)fov042
[http://dx.doi.org/10.1093/femsyr/fov042] [PMID:  26066553] 
[39] 
Muñoz-Duarte, A.R.; Castrejón-Jiménez, N.S.; Baltierra-Uribe, S.L.; Pérez-Rangel, S.J.; Carapia-Minero, N.; Castañeda-Sánchez, J.I.; Luna-Herrera, J.; López-Santiago, R.; Rodríguez-Tovar, A.V.; García-Pérez, B.E. Candida glabrata survives and replicates in human osteoblasts. Pathog. Dis.,  2016, 74(4)ftw030
[http://dx.doi.org/10.1093/femspd/ftw030] [PMID:  27073253] 
[40] 
Warren, T.A.; McTaggart, L.; Richardson, S.E.; Zhang, S.X. Candida bracarensis bloodstream infection in an immunocompromised patient. J. Clin. Microbiol.,  2010, 48(12), 4677-4679.
[http://dx.doi.org/10.1128/JCM.01447-10] [PMID:  20881164] 
[41] 
Pemán, J.; Cantón, E.; Quindós, G.; Eraso, E.; Alcoba, J.; Guinea, J.; Merino, P.; Ruiz-Pérez-de-Pipaon, M.T.; Pérez-del-Molino, L.; Linares-Sicilia, M.J.; Marco, F.; García, J.; Roselló, E.M.; Gómez-G-de-la-Pedrosa, E.; Borrell, N.; Porras, A.; Yagüe, G. Epidemiology, species distribution and in vitro antifungal susceptibility of fungaemia in a Spanish multicentre prospective survey. J. Antimicrob. Chemother.,  2012, 67(5), 1181-1187.
[http://dx.doi.org/10.1093/jac/dks019] [PMID:  22351683] 
[42] 
Li, J.; Shan, Y.; Fan, S.; Liu, X. Prevalence of candida nivariensis and candida bracarensis in vulvovaginal candidiasis. Mycopathologia,  2014, 178(3-4), 279-283.
[http://dx.doi.org/10.1007/s11046-014-9800-2] [PMID:  25118875] 
[43] 
Hachem, R.; Hanna, H.; Kontoyiannis, D.; Jiang, Y.; Raad, I. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer,  2008, 112(11), 2493-2499.
[http://dx.doi.org/10.1002/cncr.23466] [PMID:  18412153] 
[44] 
Cuenca-Estrella, M.; Gomez-Lopez, A.; Isla, G.; Rodriguez, D.; Almirante, B.; Pahissa, A.; Rodriguez-Tudela, J.L. Prevalence of Candida bracarensis and Candida nivariensis in a Spanish collection of yeasts: comparison of results from a reference centre and from a population-based surveillance study of candidemia. Med. Mycol.,  2011, 49(5), 525-529.
[PMID:  21198347] 
[45] 
Horn, D.L.; Neofytos, D.; Anaissie, E.J.; Fishman, J.A.; Steinbach, W.J.; Olyaei, A.J.; Marr, K.A.; Pfaller, M.A.; Chang, C.H.; Webster, K.M. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis.,  2009, 48(12), 1695-1703.
[http://dx.doi.org/10.1086/599039] [PMID:  19441981] 
[46] 
vanden Bossche, H.; Marichal, P.; Odds, F.C.; Le Jeune, L.; Coene, M.C. Characterization of an azole-resistant Candida glabrata isolate. Antimicrob. Agents Chemother.,  1992, 36(12), 2602-2610.
[http://dx.doi.org/10.1128/AAC.36.12.2602] [PMID:  1482129] 
[47] 
Calderone, R.A. Candida and candidiasis; ASM Press: Washington, DC, 2002, pp. 349-383.
[48] 
Marichal, P.; Vanden Bossche, H.; Odds, F.C.; Nobels, G.; Warnock, D.W.; Timmerman, V.; Van Broeckhoven, C.; Fay, S.; Mose-Larsen, P. Molecular biological characterization of an azole-resistant Candida glabrata isolate. Antimicrob. Agents Chemother.,  1997, 41(10), 2229-2237.
[http://dx.doi.org/10.1128/AAC.41.10.2229] [PMID:  9333053] 
[49] 
Sanguinetti, M.; Posteraro, B.; Fiori, B.; Ranno, S.; Torelli, R.; Fadda, G. Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob. Agents Chemother.,  2005, 49(2), 668-679.
[http://dx.doi.org/10.1128/AAC.49.2.668-679.2005] [PMID:  15673750] 
[50] 
Vallabhaneni, S.; Cleveland, A.A.; Farley, M.M.; Harrison, L.H.; Schaffner, W.; Beldavs, Z.G.; Derado, G.; Pham, C.D.; Lockhart, S.R.; Smith, R.M. Epidemiology and risk factors for echinocandin nonsusceptible Candida glabrata bloodstream infections: data from a large multisite population-based Candidemia Surveillance Program, 2008-2014. Open Forum Infect. Dis.,  2015, 2(4)ofv163
[http://dx.doi.org/10.1093/ofid/ofv163] [PMID:  26677456] 
[51] 
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(12), 1724-1732.
[http://dx.doi.org/10.1093/cid/cit136] [PMID:  23487382] 
[52] 
Lewis, J.S., II; Wiederhold, N.P.; Wickes, B.L.; Patterson, T.F.; Jorgensen, J.H. Rapid emergence of echinocandin resistance in Candida glabrata resulting in clinical and microbiologic failure. Antimicrob. Agents Chemother.,  2013, 57(9), 4559-4561.
[http://dx.doi.org/10.1128/AAC.01144-13] [PMID:  23817368] 
[53] 
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.; Zaoutis, T.E.; Sobel, J.D. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis.,  2016, 62(4), 1-50.
[http://dx.doi.org/10.1093/cid/civ1194] 
[54] 
Laniado-Laborín, R.; Cabrales-Vargas, M.N. Amphotericin B: side effects and toxicity. Rev. Iberoam. Micol.,  2009, 26(4), 223-227.
[http://dx.doi.org/10.1016/j.riam.2009.06.003] [PMID:  19836985] 
[55] 
Denardi, L.B.; Keller, J.T.; Oliveira, V.; Mario, D.A.N.; Santurio, J.M.; Alves, S.H. Activity of combined antifungal agents against multidrug-resistant Candida glabrata strains. Mycopathologia,  2017, 182(9-10), 819-828.
[http://dx.doi.org/10.1007/s11046-017-0141-9] [PMID:  28493006] 
[56] 
Loreto, E.S.; Scheid, L.A.; Nogueira, C.W.; Zeni, G.; Santurio, J.M.; Alves, S.H. Candida dubliniensis: epidemiology and phenotypic methods for identification. Mycopathologia,  2010, 169(6), 431-443.
[http://dx.doi.org/10.1007/s11046-010-9286-5] [PMID:  20490751] 
[57] 
Coleman, D.C.; Moran, G.P.; McManus, B.A.; Sullivan, D.J. Mechanisms of antifungal drug resistance in Candida dubliniensis. Future Microbiol.,  2010, 5(6), 935-949.
[http://dx.doi.org/10.2217/fmb.10.51] [PMID:  20521937] 
[58] 
Sullivan, D.J.; Westerneng, T.J.; Haynes, K.A.; Bennett, D.E.; Coleman, D.C. Candida dubliniensis sp. nov.: phenotypic and molecular characterization of a novel species associated with oral candidosis in HIV-infected individuals. Microbiology,  1995, 141, 1507-1521.
[http://dx.doi.org/10.1099/13500872-141-7-1507] 
[59] 
Odds, F.C.; Van Nuffel, L.; Dams, G. Prevalence of Candida dubliniensis isolates in a yeast stock collection. J. Clin. Microbiol.,  1998, 36(10), 2869-2873.
[PMID:  9738035] 
[60] 
Polacheck, I.; Strahilevitz, J.; Sullivan, D.; Donnelly, S.; Salkin, I.F.; Coleman, D.C. Recovery of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Israel. J. Clin. Microbiol.,  2000, 38(1), 170-174.
[PMID:  10618082] 
[61] 
Fotedar, R.; Al-Hedaithy, S.S. Candida dubliniensis at a university hospital in Saudi Arabia. J. Clin. Microbiol.,  2003, 41(5), 1907-1911.
[http://dx.doi.org/10.1128/JCM.41.5.1907-1911.2003] [PMID:  12734225] 
[62] 
Brandt, M.E.; Harrison, L.H.; Pass, M.; Sofair, A.N.; Huie, S.; Li, R.K.; Morrison, C.J.; Warnock, D.W.; Hajjeh, R.A. Candida dubliniensis fungemia: the first four cases in North America. Emerg. Infect. Dis.,  2000, 6(1), 46-49.
[http://dx.doi.org/10.3201/eid0601.000108] [PMID:  10653569] 
[63] 
Odds, F.C.; Hanson, M.F.; Davidson, A.D.; Jacobsen, M.D.; Wright, P.; Whyte, J.A.; Gow, N.A.; Jones, B.L. One year prospective survey of Candida bloodstream infections in Scotland. J. Med. Microbiol.,  2007, 56(Pt 8), 1066-1075.
[http://dx.doi.org/10.1099/jmm.0.47239-0] [PMID:  17644714] 
[64] 
Khan, Z.; Ahmad, S.; Joseph, L.; Chandy, R. Candida dubliniensis: an appraisal of its clinical significance as a bloodstream pathogen. PLoS One,  2012, 7(3)e32952
[http://dx.doi.org/10.1371/journal.pone.0032952] [PMID:  22396802] 
[65] 
Monfredini, P.M.; Souza, A.C.R.; Cavalheiro, R.P.; Siqueira, R.A.; Colombo, A.L. Clinical impact of Candida spp. biofilm production in a cohort of patients with candidemia. Med. Mycol.,  2018, 56(7), 803-808.
[http://dx.doi.org/10.1093/mmy/myx133] [PMID:  29228246] 
[66] 
Moran, G.P.; Sullivan, D.J.; Henman, M.C.; McCreary, C.E.; Harrington, B.J.; Shanley, D.B.; Coleman, D.C. Antifungal drug susceptibilities of oral Candida dubliniensis isolates from human immunodeficiency virus (HIV)-infected and non-HIV-infected subjects and generation of stable fluconazole-resistant derivatives in vitro. Antimicrob. Agents Chemother.,  1997, 41(3), 617-623.
[http://dx.doi.org/10.1128/AAC.41.3.617] [PMID:  9056003] 
[67] 
Pinjon, E.; Jackson, C.J.; Kelly, S.L.; Sanglard, D.; Moran, G.; Coleman, D.C.; Sullivan, D.J. Reduced azole susceptibility in genotype 3 Candida dubliniensis isolates associated with increased CdCDR1 and CdCDR2 expression. Antimicrob. Agents Chemother.,  2005, 49(4), 1312-1318.
[http://dx.doi.org/10.1128/AAC.49.4.1312-1318.2005] [PMID:  15793103] 
[68] 
Pinjon, E.; Moran, G.P.; Jackson, C.J.; Kelly, S.L.; Sanglard, D.; Coleman, D.C.; Sullivan, D.J. Molecular mechanisms of itraconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother.,  2003, 47(8), 2424-2437.
[http://dx.doi.org/10.1128/AAC.47.8.2424-2437.2003] [PMID:  12878500] 
[69] 
Moran, G.P.; Sanglard, D.; Donnelly, S.M.; Shanley, D.B.; Sullivan, D.J.; Coleman, D.C. Identification and expression of multidrug transporters responsible for fluconazole resistance in Candida dubliniensis. Antimicrob. Agents Chemother.,  1998, 42(7), 1819-1830.
[http://dx.doi.org/10.1128/AAC.42.7.1819] [PMID:  9661028] 
[70] 
Wirsching, S.; Moran, G.P.; Sullivan, D.J.; Coleman, D.C.; Morschhäuser, J. MDR1-mediated drug resistance in Candida dubliniensis. Antimicrob. Agents Chemother.,  2001, 45(12), 3416-3421.
[http://dx.doi.org/10.1128/AAC.45.12.3416-3421.2001] [PMID:  11709317] 
[71] 
McManus, B.A.; Moran, G.P.; Higgins, J.A.; Sullivan, D.J.; Coleman, D.C.A.A. Ser29Leu substitution in the cytosine deaminase Fca1p is responsible for clade-specific flucytosine resistance in Candida dubliniensis. Antimicrob. Agents Chemother.,  2009, 53(11), 4678-4685.
[http://dx.doi.org/10.1128/AAC.00607-09] [PMID:  19704126] 
[72] 
Lan, L.; Xu, J. Multiple gene genealogical analyses suggest divergence and recent clonal dispersal in the opportunistic human pathogen Candida guilliermondii. Microbiology,  2006, 152(Pt 5), 1539-1549.
[http://dx.doi.org/10.1099/mic.0.28626-0] [PMID:  16622071] 
[73] 
Vaughan-Martini, A.; Kurtzman, C.P.; Meyer, S.A.; O’Neill, E.B. Two new species in the Pichia guilliermondii clade: Pichia caribbica sp. nov., the ascosporic state of Candida fermentati, and Candida carpophila comb. nov. FEMS Yeast Res.,  2005, 5(4-5), 463-469.
[http://dx.doi.org/10.1016/j.femsyr.2004.10.008] [PMID:  15691751] 
[74] 
Marcos-Zambrano, L.J.; Puig-Asensio, M.; Pérez-García, F.; Escribano, P.; Sánchez-Carrillo, C.; Zaragoza, O.; Padilla, B.; Cuenca-Estrella, M.; Almirante, B.; Martín-Gómez, M.T.; Muñoz, P.; Bouza, E.; Guinea, J. Candida guilliermondii complex is characterized by high antifungal resistance but low mortality in 22 cases of candidemia. Antimicrob. Agents Chemother.,  2017, 61(7), 1-10.
[http://dx.doi.org/10.1128/AAC.00099-17] [PMID:  28438935] 
[75] 
Ghannoum, M.A.; Hajjeh, R.A.; Scher, R.; Konnikov, N.; Gupta, A.K.; Summerbell, R.; Sullivan, S.; Daniel, R.; Krusinski, P.; Fleckman, P.; Rich, P.; Odom, R.; Aly, R.; Pariser, D.; Zaiac, M.; Rebell, G.; Lesher, J.; Gerlach, B.; Ponce-De-Leon, G.F.; Ghannoum, A.; Warner, J.; Isham, N.; Elewski, B. A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J. Am. Acad. Dermatol.,  2000, 43(4), 641-648.
[http://dx.doi.org/10.1067/mjd.2000.107754] [PMID:  11004620] 
[76] 
Pfaller, M.A.; Diekema, D.J.; Mendez, M.; Kibbler, C.; Erzsebet, P.; Chang, S-C.; Gibbs, D.L.; Newell, V.A. Candida guilliermondii, an opportunistic fungal pathogen with decreased susceptibility to fluconazole: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J. Clin. Microbiol.,  2006, 44(10), 3551-3556.
[http://dx.doi.org/10.1128/JCM.00865-06] [PMID:  17021081] 
[77] 
Colombo, A.L.; Júnior, J.N.A.; Guinea, J. Emerging multidrug-resistant Candida species. Curr. Opin. Infect. Dis.,  2017, 30(6), 528-538.
[http://dx.doi.org/10.1097/QCO.0000000000000411] [PMID:  29095200] 
[78] 
Chen, C.Y.; Huang, S.Y.; Tang, J.L.; Tsay, W.; Yao, M.; Ko, B.S.; Chou, W.C.; Tien, H.F.; Hsueh, P.R. Clinical features of patients with infections caused by Candida guilliermondii and Candida fermentati and antifungal susceptibility of the isolates at a medical centre in Taiwan, 2001-10. J. Antimicrob. Chemother.,  2013, 68(11), 2632-2635.
[http://dx.doi.org/10.1093/jac/dkt214] [PMID:  23766486] 
[79] 
Hirayama, T.; Miyazaki, T.; Yamagishi, Y.; Mikamo, H.; Ueda, T.; Nakajima, K.; Takesue, Y.; Higashi, Y.; Yamamoto, Y.; Kimura, M.; Araoka, H.; Taniguchi, S.; Fukuda, Y.; Matsuo, Y.; Furutani, A.; Yamashita, K.; Takazono, T.; Saijo, T.; Shimamura, S.; Yamamoto, K.; Imamura, Y.; Izumikawa, K.; Yanagihara, K.; Kohno, S.; Mukae, H. Clinical and microbiological characteristics of Candida guilliermondii and Candida fermentati. Antimicrob. Agents Chemother.,  2018, 62(6), 1-9.
[http://dx.doi.org/10.1128/AAC.02528-17] [PMID:  29581115] 
[80] 
Pfaller, M.; Neofytos, D.; Diekema, D.; Azie, N.; Meier-Kriesche, H.U.; Quan, S.P.; Horn, D. Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004-2008. Diagn. Microbiol. Infect. Dis.,  2012, 74(4), 323-331.
[http://dx.doi.org/10.1016/j.diagmicrobio.2012.10.003] [PMID:  23102556] 
[81] 
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(5), 1-5.
[http://dx.doi.org/10.1128/AAC.02644-16] [PMID:  28242659] 
[82] 
Padovan, A.C.; Melo, A.S.; Colombo, A.L. Systematic review and new insights into the molecular characterization of the Candida rugosa species complex. Fungal Genet. Biol.,  2013, 61, 33-41.
[http://dx.doi.org/10.1016/j.fgb.2013.10.007] 
[83] 
Domínguez de María, P.; Sánchez-Montero, J.M.; Sinisterra, J.V.; Alcántara, A.R. Understanding Candida rugosa lipases: an overview. Biotechnol. Adv.,  2006, 24(2), 180-196.
[http://dx.doi.org/10.1016/j.biotechadv.2005.09.003] [PMID:  16288844] 
[84] 
Singh, R.I.; Xess, I.; Mathur, P.; Behera, B.; Gupta, B.; Misra, M.C. Epidemiology of candidaemia in critically ill trauma patients: experiences of a level I trauma centre in North India. J. Med. Microbiol.,  2011, 60(Pt 3), 342-348.
[http://dx.doi.org/10.1099/jmm.0.023739-0] [PMID:  21127153] 
[85] 
Behera, B.; Singh, R.I.; Xess, I.; Mathur, P.; Hasan, F.; Misra, M.C. Candida rugosa: a possible emerging cause of candidaemia in trauma patients. Infection,  2010, 38(5), 387-393.
[http://dx.doi.org/10.1007/s15010-010-0044-x] [PMID:  20658166] 
[86] 
Pfaller, M.A.; Diekema, D.J.; Colombo, A.L.; Kibbler, C.; Ng, K.P.; Gibbs, D.L.; Newell, V.A. Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK antifungal surveillance program. J. Clin. Microbiol.,  2006, 44(10), 3578-3582.
[http://dx.doi.org/10.1128/JCM.00863-06] [PMID:  17021085] 
[87] 
Capoor, M.R.; Gupta, D.K.; Verma, P.K.; Sachdeva, H.C. Rare yeasts causing fungemia in immunocompromised and haematology patients: Case series from Delhi. Indian J. Med. Microbiol.,  2015, 33(4), 576-579.
[http://dx.doi.org/10.4103/0255-0857.167320] [PMID:  26470968] 
[88] 
Li, J.; Xu, Y.C.; Bai, F.Y. Candida pseudorugosa sp. nov., a novel yeast species from sputum. J. Clin. Microbiol.,  2006, 44(12), 4486-4490.
[http://dx.doi.org/10.1128/JCM.01391-06] [PMID:  17021068] 
[89] 
Kocyigit, I.; Unal, A.; Sipahioglu, M.H.; Tokgoz, B.; Oymak, O.; Utas, C. Peritonitis due to Candida rugosa: the first case report. Perit. Dial. Int.,  2010, 30(5), 576-577.
[http://dx.doi.org/10.3747/pdi.2010.00045] [PMID:  20829554] 
[90] 
Paredes, K.; Sutton, D.A.; Cano, J.; Fothergill, A.W.; Lawhon, S.D.; Zhang, S.; Watkins, J.P.; Guarro, J. Molecular identification and antifungal susceptibility testing of clinical isolates of the Candida rugosa species complex and proposal of the new species Candida neorugosa. J. Clin. Microbiol.,  2012, 50(7), 2397-2403.
[http://dx.doi.org/10.1128/JCM.00688-12] [PMID:  22553236] 
[91] 
Tay, S.T.; Tan, H.W.; Na, S.L.; Lim, S.L. Phenotypic and genotypic characterization of two closely related subgroups of Candida rugosa in clinical specimens. J. Med. Microbiol.,  2011, 60(Pt 11), 1591-1597.
[http://dx.doi.org/10.1099/jmm.0.032854-0] [PMID:  21700741] 
[92] 
Azevedo, A.C.; Bizerra, F.C.; da Matta, D.A.; de Almeida, L.P.; Rosas, R.; Colombo, A.L. In vitro susceptibility of a large collection of Candida Strains against fluconazole and voriconazole by using the CLSI disk diffusion assay. Mycopathologia,  2011, 171(6), 411-416.
[http://dx.doi.org/10.1007/s11046-010-9387-1] [PMID:  21181497] 
[93] 
Dubé, M.P.; Heseltine, P.N.; Rinaldi, M.G.; Evans, S.; Zawacki, B. Fungemia and colonization with nystatin-resistant Candida rugosa in a burn unit. Clin. Infect. Dis.,  1994, 18(1), 77-82.
[http://dx.doi.org/10.1093/clinids/18.1.77] [PMID:  8054438] 
[94] 
Colombo, A.L.; Melo, A.S.; Crespo Rosas, R.F.; Salomão, R.; Briones, M.; Hollis, R.J.; Messer, S.A.; Pfaller, M.A. Outbreak of Candida rugosa candidemia: an emerging pathogen that may be refractory to amphotericin B therapy. Diagn. Microbiol. Infect. Dis.,  2003, 46(4), 253-257.
[http://dx.doi.org/10.1016/S0732-8893(03)00079-8] [PMID:  12944016] 
[95] 
Satoh, K.; Makimura, K.; Hasumi, Y.; Nishiyama, Y.; Uchida, K.; Yamaguchi, H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol. Immunol.,  2009, 53(1), 41-44.
[http://dx.doi.org/10.1111/j.1348-0421.2008.00083.x] [PMID:  19161556] 
[96] 
Osei Sekyere, J. Candida auris: A systematic review and meta-analysis of current updates on an emerging multidrug-resistant pathogen. MicrobiologyOpen,  2018, 7(4)e00578
[http://dx.doi.org/10.1002/mbo3.578] [PMID:  29345117] 
[97] 
Morales-López, S.E.; Parra-Giraldo, C.M.; Ceballos-Garzón, A.; Martínez, H.P.; Rodríguez, G.J.; Álvarez-Moreno, C.A.; Rodríguez, J.Y. Invasive infections with multidrug-resistant yeast Candida auris, Colombia. Emerg. Infect. Dis.,  2017, 23(1), 162-164.
[http://dx.doi.org/10.3201/eid2301.161497] [PMID:  27983941] 
[98] 
Rudramurthy, S.M.; Jatana, M.; Singh, R.; Chakrabarti, A. In vitro antifungal activity of Indian liposomal amphotericin B against clinical isolates of emerging species of yeast and moulds, and its comparison with amphotericin B deoxycholate, voriconazole, itraconazole and fluconazole. Mycoses,  2013, 56(1), 39-46.
[http://dx.doi.org/10.1111/j.1439-0507.2012.02197.x] [PMID:  22519679] 
[99] 
Schelenz, S.; Hagen, F.; Rhodes, J.L.; Abdolrasouli, A.; Chowdhary, A.; Hall, A.; Ryan, L.; Shackleton, J.; Trimlett, R.; Meis, J.F.; Armstrong-James, D.; Fisher, M.C. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob. Resist. Infect. Control,  2016, 5, 1-7.
[http://dx.doi.org/10.1186/s13756-016-0132-5] 
[100] 
Magobo, R.E.; Corcoran, C.; Seetharam, S.; Govender, N.P. Candida auris-associated candidemia, South Africa. Emerg. Infect. Dis.,  2014, 20(7), 1250-1251.
[http://dx.doi.org/10.3201/eid2007.131765] [PMID:  24963796] 
[101] 
Chowdhary, A.; Voss, A.; Meis, J.F. Multidrug-resistant Candida auris: ‘new kid on the block’ in hospital-associated infections? J. Hosp. Infect.,  2016, 94(3), 209-212.
[http://dx.doi.org/10.1016/j.jhin.2016.08.004] [PMID:  27634564] 
[102] 
Chowdhary, A.; Sharma, C.; Meis, J.F. Candida auris: A rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS Pathog.,  2017, 13(5)e1006290
[http://dx.doi.org/10.1371/journal.ppat.1006290] [PMID:  28542486] 
[103] 
 Candida auris. https://www.cdc.gov/fungal/candida-auris/index.html (Accessed 2018).
[104] 
Healey, K.R.; Kordalewska, M.; Jiménez Ortigosa, C.; Singh, A.; Berrío, I.; Chowdhary, A.; Perlin, D.S. Limited ERG11 mutations identified in isolates of Candida auris directly contribute to reduced azole susceptibility. Antimicrob. Agents Chemother.,  2018, 62(10), 1-4.
[http://dx.doi.org/10.1128/AAC.01427-18] [PMID:  30082281] 
[105] 
Chowdhary, A.; Prakash, A.; Sharma, C.; Kordalewska, M.; Kumar, A.; Sarma, S.; Tarai, B.; Singh, A.; Upadhyaya, G.; Upadhyay, S.; Yadav, P.; Singh, P.K.; Khillan, V.; Sachdeva, N.; Perlin, D.S.; Meis, J.F. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J. Antimicrob. Chemother.,  2018, 73(4), 891-899.
[http://dx.doi.org/10.1093/jac/dkx480] [PMID:  29325167] 
[106] 
Ben-Ami, R.; Berman, J.; Novikov, A.; Bash, E.; Shachor-Meyouhas, Y.; Zakin, S.; Maor, Y.; Tarabia, J.; Schechner, V.; Adler, A.; Finn, T. Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg. Infect. Dis.,  2017, 23(1), 195-203.
[PMID:  28098529] 
[107] 
Kean, R.; Delaney, C.; Sherry, L.; Borman, A.; Johnson, E.M.; Richardson, M.D.; Rautemaa-Richardson, R.; Williams, C.; Ramage, G. Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. MSphere,  2018, 3(4), 1-14.
[http://dx.doi.org/10.1128/mSphere.00334-18] [PMID:  29997121] 
[108] 
Lewis, R.E. Current concepts in antifungal pharmacology. Mayo Clin. Proc.,  2011, 86(8), 805-817.
[http://dx.doi.org/10.4065/mcp.2011.0247] [PMID:  21803962] 
[109] 
Cendejas-Bueno, E.; Kolecka, A.; Alastruey-Izquierdo, A.; Theelen, B.; Groenewald, M.; Kostrzewa, M.; Cuenca-Estrella, M.; Gómez-López, A.; Boekhout, T. Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts. J. Clin. Microbiol.,  2012, 50(11), 3641-3651.
[http://dx.doi.org/10.1128/JCM.02248-12] [PMID:  22952266] 
[110] 
Lavarde, V.; Daniel, F.; Saez, H.; Arnold, M.; Faguer, B. Peritonite mycosique a Torulopsis haemulonii. Bull. Soc. Fr. Mycol. Med.,  1984, 13, 173-176.
[111] 
Khan, Z.U.; Al-Sweih, N.A.; Ahmad, S.; Al-Kazemi, N.; Khan, S.; Joseph, L.; Chandy, R. Outbreak of fungemia among neonates caused by Candida haemulonii resistant to amphotericin B, itraconazole, and fluconazole. J. Clin. Microbiol.,  2007, 45(6), 2025-2027.
[http://dx.doi.org/10.1128/JCM.00222-07] [PMID:  17428940] 
[112] 
Kim, S.; Ko, K.S.; Moon, S.Y.; Lee, M.S.; Lee, M.Y.; Son, J.S. Catheter-related candidemia caused by Candida haemulonii in a patient in long-term hospital care. J. Korean Med. Sci.,  2011, 26(2), 297-300.
[http://dx.doi.org/10.3346/jkms.2011.26.2.297] [PMID:  21286025] 
[113] 
Ramos, L.S.; Figueiredo-Carvalho, M.H.G.; Barbedo, L.S.; Ziccardi, M.; Chaves, A.L.S.; Zancopé-Oliveira, R.M.; Pinto, M.R.; Sgarbi, D.B.G.; Dornelas-Ribeiro, M.; Branquinha, M.H.; Santos, A.L.S. Candida haemulonii complex: species identification and antifungal susceptibility profiles of clinical isolates from Brazil. J. Antimicrob. Chemother.,  2015, 70(1), 111-115.
[http://dx.doi.org/10.1093/jac/dku321] [PMID:  25134720] 
[114] 
Boatto, H.F.; Cavalcanti, S.D.; Del Negro, G.M.; Girão, M.J.; Francisco, E.C.; Ishida, K.; Gompertz, O.F. Candida duobushaemulonii: an emerging rare pathogenic yeast isolated from recurrent vulvovaginal candidiasis in Brazil. Mem. Inst. Oswaldo Cruz,  2016, 111(6), 407-410.
[http://dx.doi.org/10.1590/0074-02760160166] [PMID:  27304096] 
[115] 
de Almeida, J.N., Jr; Assy, J.G.; Levin, A.S.; Del Negro, G.M.; Giudice, M.C.; Tringoni, M.P.; Thomaz, D.Y.; Motta, A.L.; Abdala, E.; Pierroti, L.C.; Strabelli, T.; Munhoz, A.L.; Rossi, F.; Benard, G. Candida haemulonii complex species, Brazil, January 2010-March 2015. Emerg. Infect. Dis.,  2016, 22(3), 561-563.
[http://dx.doi.org/10.3201/eid2203.151610] [PMID:  26891028] 
[116] 
Hou, X.; Xiao, M.; Chen, S.C.; Wang, H.; Cheng, J.W.; Chen, X.X.; Xu, Z.P.; Fan, X.; Kong, F.; Xu, Y.C. Identification and antifungal susceptibility profiles of Candida haemulonii species complex clinical isolates from a multicenter study in China. J. Clin. Microbiol.,  2016, 54(11), 2676-2680.
[http://dx.doi.org/10.1128/JCM.01492-16] [PMID:  27535688] 
[117] 
Xess, I.; Jain, N.; Hasan, F.; Mandal, P.; Banerjee, U. Epidemiology of candidemia in a tertiary care centre of north India: 5-year study. Infection,  2007, 35(4), 256-259.
[http://dx.doi.org/10.1007/s15010-007-6144-6] [PMID:  17646917] 
[118] 
Oberoi, J.K.; Wattal, C.; Goel, N.; Raveendran, R.; Datta, S.; Prasad, K. Non-albicans Candida species in blood stream infections in a tertiary care hospital at New Delhi, India. Indian J. Med. Res.,  2012, 136(6), 997-1003.
[PMID:  23391796] 
[119] 
Kumar, A.; Prakash, A.; Singh, A.; Kumar, H.; Hagen, F.; Meis, J.F.; Chowdhary, A. Candida haemulonii species complex: an emerging species in India and its genetic diversity assessed with multilocus sequence and amplified fragment-length polymorphism analyses. Emerg. Microbes Infect.,  2016, 5(5)e49
[http://dx.doi.org/10.1038/emi.2016.49] [PMID:  27222324] 
[120] 
García-Martos, P.; Domínguez, I.; Marín, P.; García-Agudo, R.; Aoufi, S.; Mira, J. Antifungal susceptibility of emerging yeast pathogens. Enferm. Infecc. Microbiol. Clin.,  2001, 19(6), 249-256.
[PMID:  11440661] 
[121] 
Ruan, S.Y.; Kuo, Y.W.; Huang, C.T.; Hsiue, H.C.; Hsueh, P.R. Infections due to Candida haemulonii: species identification, antifungal susceptibility and outcomes. Int. J. Antimicrob. Agents,  2010, 35(1), 85-88.
[http://dx.doi.org/10.1016/j.ijantimicag.2009.08.009] [PMID:  19786341] 
[122] 
Gomez-Lopez, A.; Buitrago, M.J.; Rodriguez-Tudela, J.L.; Cuenca-Estrella, M. In vitro antifungal susceptibility pattern and ergosterol content in clinical yeast strains. Rev. Iberoam. Micol.,  2011, 28(2), 100-103.
[http://dx.doi.org/10.1016/j.riam.2010.12.003] [PMID:  21251996] 
[123] 
Rodero, L.; Cuenca-Estrella, M.; Córdoba, S.; Cahn, P.; Davel, G.; Kaufman, S.; Guelfand, L.; Rodríguez-Tudela, J.L. Transient fungemia caused by an amphotericin B-resistant isolate of Candida haemulonii. J. Clin. Microbiol.,  2002, 40(6), 2266-2269.
[http://dx.doi.org/10.1128/JCM.40.6.2266-2269.2002] [PMID:  12037106] 
[124] 
Silva, L.N.; Campos-Silva, R.; Ramos, L.S.; Trentin, D.S.; Macedo, A.J.; Branquinha, M.H.; Santos, A.L.S. Virulence of Candida haemulonii complex in Galleria mellonella and efficacy of classical antifungal drugs: a comparative study with other clinically relevant non-albicans Candida species. FEMS Yeast Res.,  2018, 18(7), 1-12.
[http://dx.doi.org/10.1093/femsyr/foy082] [PMID:  30052907] 
[125] 
Crouzet, J.; Sotto, A.; Picard, E.; Lachaud, L.; Bourgeois, N. A case of Candida haemulonii osteitis: clinical features, biochemical characteristics, and antifungal resistance profile. Clin. Microbiol. Infect.,  2011, 17(7), 1068-1070.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03471.x] [PMID:  21375662] 
[126] 
Muro, M.D. Motta, Fde.A.; Burger, M.; Melo, A.S.A.; Dalla-Costa, L.M. Echinocandin resistance in two Candida haemulonii isolates from pediatric patients. J. Clin. Microbiol.,  2012, 50(11), 3783-3785.
[http://dx.doi.org/10.1128/JCM.01136-12] [PMID:  22895037] 
[127] 
Scorzoni, L. de Paula e Silva, A.C.A.; Marcos, C.M.; Assato, P.A.; de Melo, W.C.M.A.; de Oliveira, H.C.; Costa-Orlandi, C.B.; Mendes-Giannini, M.J.S.; Fusco-Almeida, A.M. Antifungal therapy: new advances in the understanding and treatment of mycosis. Front. Microbiol.,  2017, 8, 1-23.
[http://dx.doi.org/10.3389/fmicb.2017.00036] 
[128] 
Roemer, T.; Krysan, D.J. Antifungal drug development: challenges, unmet clinical needs, and new approaches. Cold Spring Harb. Perspect. Med.,  2014, 4(5), 1-15.
[http://dx.doi.org/10.1101/cshperspect.a019703] [PMID:  24789878] 
[129] 
Miceli, M.H.; Kauffman, C.A. Isavuconazole: a new broad-spectrum triazole antifungal agent. Clin. Infect. Dis.,  2015, 61(10), 1558-1565.
[http://dx.doi.org/10.1093/cid/civ571] [PMID:  26179012] 
[130] 
Warrilow, A.G.S.; Hull, C.M.; Parker, J.E.; Garvey, E.P.; Hoekstra, W.J.; Moore, W.R.; Schotzinger, R.J.; Kelly, D.E.; Kelly, S.L. The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme. Antimicrob. Agents Chemother.,  2014, 58(12), 7121-7127.
[http://dx.doi.org/10.1128/AAC.03707-14] [PMID:  25224009] 
[131] 
Garvey, E.P.; Hoekstra, W.J.; Moore, W.R.; Schotzinger, R.J.; Long, L.; Ghannoum, M.A. VT-1161 dosed once daily or once weekly exhibits potent efficacy in treatment of dermatophytosis in a guinea pig model. Antimicrob. Agents Chemother.,  2015, 59(4), 1992-1997.
[http://dx.doi.org/10.1128/AAC.04902-14] [PMID:  25605358] 
[132] 
Lockhart, S.R.; Fothergill, A.W.; Iqbal, N.; Bolden, C.B.; Grossman, N.T.; Garvey, E.P.; Brand, S.R.; Hoekstra, W.J.; Schotzinger, R.J.; Ottinger, E.; Patterson, T.F.; Wiederhold, N.P. The investigational fungal Cyp51 inhibitor VT-1129 demonstrates potent in vitro activity against Cryptococcus neoformans and Cryptococcus gattii. Antimicrob. Agents Chemother.,  2016, 60(4), 2528-2531.
[http://dx.doi.org/10.1128/AAC.02770-15] [PMID:  26787697] 
[133] 
Wiederhold, N.P. Antifungal resistance: current trends and future strategies to combat. Drug Res.,  2017, 10, 249-259.
[http://dx.doi.org/10.2147/IDR.S124918] 
[134] 
Wiederhold, N.P. The antifungal arsenal: alternative drugs and future targets. Int. J. Antimicrob. Agents,  2018, 51(3), 333-339.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.09.002] [PMID:  28890395] 
[135] 
Perfect, J.R. The antifungal pipeline: a reality check. Nat. Rev. Drug Discov.,  2017, 16(9), 603-616.
[http://dx.doi.org/10.1038/nrd.2017.46] [PMID:  28496146] 
[136] 
Gonzalez-Lara, M.F.; Sifuentes-Osornio, J.; Ostrosky-Zeichner, L. Drugs in clinical development for fungal infections. Drugs,  2017, 77(14), 1505-1518.
[http://dx.doi.org/10.1007/s40265-017-0805-2] [PMID:  28840541] 
[137] 
Hoekstra, W.J.; Garvey, E.P.; Moore, W.R.; Rafferty, S.W.; Yates, C.M.; Schotzinger, R.J. Design and optimization of highly-selective fungal CYP51 inhibitors. Bioorg. Med. Chem. Lett.,  2014, 24(15), 3455-3458.
[http://dx.doi.org/10.1016/j.bmcl.2014.05.068] [PMID:  24948565] 
[138] 
Warrilow, A.G.S.; Parker, J.E.; Price, C.L.; Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Wiederhold, N.P.; Nes, W.D.; Kelly, D.E.; Kelly, S.L. The tetrazole VT-1161 is a potent inhibitor of Trichophyton rubrum through its inhibition of T. rubrum CYP51. Antimicrob. Agents Chemother.,  2017, 61(7), 1-11.
[http://dx.doi.org/10.1128/AAC.00333-17] [PMID:  28483956] 
[139] 
Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Sobel, J.D.; Lilly, E.A.; Fidel, P.L., Jr Efficacy of the clinical agent VT-1161 against fluconazole-sensitive and -resistant Candida albicans in a murine model of vaginal candidiasis. Antimicrob. Agents Chemother.,  2015, 59(9), 5567-5573.
[http://dx.doi.org/10.1128/AAC.00185-15] [PMID:  26124165] 
[140] 
Break, T.J.; Desai, J.V.; Natarajan, M.; Ferre, E.M.N.; Henderson, C.; Zelazny, A.M.; Siebenlist, U.; Hoekstra, W.J.; Schotzinger, R.J.; Garvey, E.P.; Lionakis, M.S. VT-1161 protects mice against oropharyngeal candidiasis caused by fluconazole-susceptible andresistant Candida albicans. J. Antimicrob. Chemother.,  2018, 73(1), 151-155.
[http://dx.doi.org/10.1093/jac/dkx352] [PMID:  29040636] 
[141] 
Shubitz, L.F.; Trinh, H.T.; Galgiani, J.N.; Lewis, M.L.; Fothergill, A.W.; Wiederhold, N.P.; Barker, B.M.; Lewis, E.R.; Doyle, A.L.; Hoekstra, W.J.; Schotzinger, R.J.; Garvey, E.P. Evaluation of VT-1161 for treatment of coccidioidomycosis in murine infection models. Antimicrob. Agents Chemother.,  2015, 59(12), 7249-7254.
[http://dx.doi.org/10.1128/AAC.00593-15] [PMID:  26369964] 
[142] 
Shubitz, L.F.; Roy, M.E.; Trinh, H.T.; Hoekstra, W.J.; Schotzinger, R.J.; Garvey, E.P. Efficacy of the investigational antifungal VT-1161 in treating naturally occurring coccidioidomycosis in dogs. Antimicrob. Agents Chemother.,  2017, 61(5), 1-8.
[http://dx.doi.org/10.1128/AAC.00111-17] [PMID:  28289027] 
[143] 
Gebremariam, T.; Wiederhold, N.P.; Fothergill, A.W.; Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Patterson, T.F.; Filler, S.G.; Ibrahim, A.S. VT-1161 protects immunosuppressed mice from Rhizopus arrhizus var. arrhizus infection. Antimicrob. Agents Chemother.,  2015, 59(12), 7815-7817.
[http://dx.doi.org/10.1128/AAC.01437-15] [PMID:  26369977] 
[144] 
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(3), 1-3.
[http://dx.doi.org/10.1128/AAC.01817-16] [PMID:  27956419] 
[145] 
Nielsen, K.; Vedula, P.; Smith, K.D.; Meya, D.B.; Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Boulware, D.R. Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs. Med. Mycol.,  2017, 55(4), 453-456.
[http://dx.doi.org/ 10.1093/mmy/myw089] [PMID:  27664991] 
[146] 
Warrilow, A.G.S.; Parker, J.E.; Price, C.L.; Nes, W.D.; Garvey, E.P.; Hoekstra, W.J.; Schotzinger, R.J.; Kelly, D.E.; Kelly, S.L. The investigational drug VT-1129 is a highly potent inhibitor of Cryptococcus species CYP51 but only weakly inhibits the human enzyme. Antimicrob. Agents Chemother.,  2016, 60(8), 4530-4538.
[http://dx.doi.org/10.1128/AAC.00349-16] [PMID:  27161631] 
[147] 
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.; Schotzinger, R.J.; Jaramillo, R.; Olivo, M.; Kirkpatrick, W.R.; Patterson, T.F. The fungal Cyp51 inhibitor VT-1129 is efficacious in an experimental model of cryptococcal meningitis. Antimicrob. Agents Chemother.,  2018, 62(9), 1-10.
[http://dx.doi.org/10.1128/AAC.01071-18] [PMID:  29987152] 
[148] 
Wiederhold, N.P.; Xu, X.; Wang, A.; Najvar, L.K.; Garvey, E.P.; Ottinger, E.A.; Alimardanov, A.; Cradock, J.; Behnke, M.; Hoekstra, W.J.; Brand, S.R.; Schotzinger, R.J.; Jaramillo, R.; Olivo, M.; Kirkpatrick, W.R.; Patterson, T.F. In vivo efficacy of VT-1129 against experimental cryptococcal meningitis with the use of a loading dose-maintenance dose administration strategy. Antimicrob. Agents Chemother.,  2018, 62(11), 1-10.
[http://dx.doi.org/10.1128/AAC.01315-18] [PMID:  30104280] 
[149] 
Hargrove, T.Y.; Garvey, E.P.; Hoekstra, W.J.; Yates, C.M.; Wawrzak, Z.; Rachakonda, G.; Villalta, F.; Lepesheva, G.I. Crystal structure of the new investigational drug candidate VT-1598 in complex with Aspergillus fumigatus sterol 14alpha-demethylase provides Iisights into its broad-spectrum antifungal activity. Antimicrob. Agents Chemother.,  2017, 61(7), 1-10.
[http://dx.doi.org/10.1128/AAC.00570-17] [PMID:  28461309] 
[150] 
Wiederhold, N.P.; Patterson, H.P.; Tran, B.H.; Yates, C.M.; Schotzinger, R.J.; Garvey, E.P. Fungal-specific Cyp51 inhibitor VT-1598 demonstrates in vitro activity against Candida and Cryptococcus species, endemic fungi, including Coccidioides species, Aspergillus species and Rhizopus arrhizus. J. Antimicrob. Chemother.,  2018, 73(2), 404-408.
[http://dx.doi.org/10.1093/jac/dkx410] [PMID:  29190379] 
[151] 
Yates, C.M.; Garvey, E.P.; Shaver, S.R.; Schotzinger, R.J.; Hoekstra, W.J. Design and optimization of highly-selective, broad spectrum fungal CYP51 inhibitors. Bioorg. Med. Chem. Lett.,  2017, 27(15), 3243-3248.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.037] [PMID:  28651982] 
[152] 
Wiederhold, N.P.; Shubitz, L.F.; Najvar, L.K.; Jaramillo, R.; Olivo, M.; Catano, G.; Trinh, H.T.; Yates, C.M.; Schotzinger, R.J.; Garvey, E.P.; Patterson, T.F. The novel fungal Cyp51 inhibitor VT-1598 is efficacious in experimental models of central nervous system coccidioidomycosis caused by Coccidioides posadasii and Coccidioides immitis. Antimicrob. Agents Chemother.,  2018, 62(4), 1-7.
[http://dx.doi.org/10.1128/AAC.02258-17] [PMID:  29437615] 
[153] 
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(10), 2815-2822.
[http://dx.doi.org/10.1093/jac/dky242] [PMID:  29947783] 
[154] 
Break, T.J.; Desai, J.V.; Healey, K.R.; Natarajan, M.; Ferre, E.M.N.; Henderson, C.; Zelazny, A.; Siebenlist, U.; Yates, C.M.; Cohen, O.J.; Schotzinger, R.J.; Perlin, D.S.; Garvey, E.P.; Lionakis, M.S. VT-1598 inhibits the in vitro growth of mucosal Candida strains and protects against fluconazole-susceptible and -resistant oral candidiasis in IL-17 signalling-deficient mice. J. Antimicrob. Chemother.,  2018, 73(8), 2089-2094.
[http://dx.doi.org/10.1093/jac/dky170] [PMID:  29788070] 
[155] 
U.S. National Library of Medicine - ClinicalTrials. Available from:. https://clinicaltrials.gov/ct2/home (Accessed on 2015).
[156] 
Sofjan, A.K.; Mitchell, A.; Shah, D.N.; Nguyen, T.; Sim, M.; Trojcak, A.; Beyda, N.D.; Garey, K.W. Rezafungin (CD101), a next-generation echinocandin: A systematic literature review and assessment of possible place in therapy. J. Glob. Antimicrob. Resist.,  2018, 14, 58-64.
[http://dx.doi.org/ 10.1016/j.jgar.2018.02.013] 
[157] 
Pfaller, M.A.; Messer, S.A.; Rhomberg, P.R.; Jones, R.N.; Castanheira, M. Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates. J. Antimicrob. Chemother.,  2016, 71(10), 2868-2873.
[http://dx.doi.org/10.1093/jac/dkw214] [PMID:  27287236] 
[158] 
Zhao, Y.; Perez, W.B.; Jiménez-Ortigosa, C.; Hough, G.; Locke, J.B.; Ong, V.; Bartizal, K.; Perlin, D.S. CD101: a novel long-acting echinocandin. Cell. Microbiol.,  2016, 18(9), 1308-1316.
[http://dx.doi.org/10.1111/cmi.12640] [PMID:  27354115] 
[159] 
Pfaller, M.A.; Messer, S.A.; Rhomberg, P.R.; Castanheira, M. Activity of a long-acting echinocandin (CD101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the SENTRY 2014 Antifungal Surveillance Program. Antimicrob. Agents Chemother.,  2017, 61(3), 1-7.
[http://dx.doi.org/10.1128/AAC.02045-16] [PMID:  28052853] 
[160] 
Pfaller, M.A.; Messer, S.A.; Rhomberg, P.R.; Castanheira, M. CD101, a long-acting echinocandin, and comparator antifungal agents tested against a global collection of invasive fungal isolates in the SENTRY 2015 Antifungal Surveillance Program. Int. J. Antimicrob. Agents,  2017, 50(3), 352-358.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.03.028] [PMID:  28689871] 
[161] 
Berkow, E.L.; Lockhart, S.R. Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris. Diagn. Microbiol. Infect. Dis.,  2018, 90(3), 196-197.
[http://dx.doi.org/10.1016/j.diagmicrobio.2017.10.021] [PMID:  29307565] 
[162] 
Hall, D.; Bonifas, R.; Stapert, L.; Thwaites, M.; Shinabarger, D.L.; Pillar, C.M. In vitro potency and fungicidal activity of CD101, a novel echinocandin, against recent clinical isolates of Candida spp. Diagn. Microbiol. Infect. Dis.,  2017, 89(3), 205-211.
[http://dx.doi.org/10.1016/j.diagmicrobio.2017.07.007] [PMID:  28826987] 
[163] 
Arendrup, M.C.; Meletiadis, J.; Zaragoza, O.; Jørgensen, K.M.; Marcos-Zambrano, L.J.; Kanioura, L.; Cuenca-Estrella, M.; Mouton, J.W.; Guinea, J. Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method. Clin. Microbiol. Infect.,  2018, 24(11), 1200-1204.
[http://dx.doi.org/10.1016/j.cmi.2018.02.021] [PMID:  29505881] 
[164] 
Locke, J.B.; Almaguer, A.L.; Donatelli, J.L.; Bartizal, K.F. Time-kill kinetics of rezafungin (CD101) in vagina-simulative medium for fluconazole-susceptible and fluconazole-resistant Candida albicans and non-albicans Candida species. Infect. Dis. Obstet. Gynecol.,  2018, 20187040498
[http://dx.doi.org/10.1155/2018/7040498] [PMID:  29681727] 
[165] 
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(11), 3063-3067.
[http://dx.doi.org/10.1093/jac/dky280] [PMID:  30032217] 
[166] 
Boikov, D.A.; Locke, J.B.; James, K.D.; Bartizal, K.; Sobel, J.D. In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis. J. Antimicrob. Chemother.,  2017, 72(5), 1355-1358.
[http://dx.doi.org/10.1093/jac/dkx008] [PMID:  28158577] 
[167] 
Locke, J.B.; Almaguer, A.L.; Zuill, D.E.; Bartizal, K. Characterization of in vitro resistance development to the novel echinocandin CD101 in Candida species. Antimicrob. Agents Chemother.,  2016, 60(10), 6100-6107.
[http://dx.doi.org/10.1128/AAC.00620-16] [PMID:  27480852] 
[168] 
Chandra, J.; Ghannoum, M.A. CD101, a novel echinocandin, possesses potent antibiofilm activity against early and mature Candida albicans biofilms. Antimicrob. Agents Chemother.,  2018, 62(2), 1-9.
[PMID:  29133552] 
[169] 
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(11), 6872-6879.
[http://dx.doi.org/10.1128/AAC.00701-16] [PMID:  27620474] 
[170] 
Lepak, A.J.; Zhao, M.; VanScoy, B.; Ambrose, P.G.; Andes, D.R. Pharmacodynamics of a long-acting echinocandin, CD101, in a neutropenic invasive-candidiasis murine model using an extended-interval dosing Ddsign. Antimicrob. Agents Chemother.,  2018, 62(2), 1-10.
[PMID:  29203480] 
[171] 
Hager, C.L.; Larkin, E.L.; Long, L.A.; Ghannoum, M.A. Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model. J. Antimicrob. Chemother.,  2018, 73(8), 2085-2088.
[http://dx.doi.org/10.1093/jac/dky153] [PMID:  29897469] 
[172] 
Krasowska, A.; Sigler, K. How microorganisms use hydrophobicity and what does this mean for human needs? Front. Cell. Infect. Microbiol.,  2014, 4, 112.
[http://dx.doi.org/10.3389/fcimb.2014.00112] 
[173] 
Pfaller, M.A.; Messer, S.A.; Motyl, M.R.; Jones, R.N.; Castanheira, M. Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST). J. Antimicrob. Chemother.,  2013, 68(4), 858-863.
[http://dx.doi.org/10.1093/jac/dks466] [PMID:  23190764] 
[174] 
Pfaller, M.A.; Messer, S.A.; Motyl, M.R.; Jones, R.N.; Castanheira, M. In vitro activity of a new oral glucan synthase inhibitor (MK-3118) tested against Aspergillus spp. by CLSI and EUCAST broth microdilution methods. Antimicrob. Agents Chemother.,  2013, 57(2), 1065-1068.
[http://dx.doi.org/10.1128/AAC.01588-12] [PMID:  23229479] 
[175] 
Jiménez-Ortigosa, C.; Paderu, P.; Motyl, M.R.; Perlin, D.S. Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates. Antimicrob. Agents Chemother.,  2014, 58(2), 1248-1251.
[http://dx.doi.org/10.1128/AAC.02145-13] [PMID:  24323472] 
[176] 
Scorneaux, B.; Angulo, D.; Borroto-Esoda, K.; Ghannoum, M.; Peel, M.; Wring, S. SCY-078 is fungicidal against Candida species in time-kill studies. Antimicrob. Agents Chemother.,  2017, 61(3), 1-10.
[http://dx.doi.org/10.1128/AAC.01961-16] [PMID:  28069658] 
[177] 
Marcos-Zambrano, L.J.; Gómez-Perosanz, M.; Escribano, P.; Bouza, E.; Guinea, J. The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp. J. Antimicrob. Chemother.,  2017, 72(7), 1969-1976.
[http://dx.doi.org/10.1093/jac/dkx010] [PMID:  28175309] 
[178] 
Larkin, E.; Hager, C.; Chandra, J.; Mukherjee, P.K.; Retuerto, M.; Salem, I.; Long, L.; Isham, N.; Kovanda, L.; Borroto-Esoda, K.; Wring, S.; Angulo, D.; Ghannoum, M. The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation. Antimicrob. Agents Chemother.,  2017, 61(5), 1-13.
[http://dx.doi.org/10.1128/AAC.02396-16] [PMID:  28223375] 
[179] 
Berkow, E.L.; Angulo, D.; Lockhart, S.R. In vitro activity of a novel glucan synthase inhibitor, SCY-078, against clinical isolates of Candida auris. Antimicrob. Agents Chemother.,  2017, 61(7), 1-2.
[http://dx.doi.org/10.1128/AAC.00435-17] [PMID:  28483955] 
[180] 
Pfaller, M.A.; Messer, S.A.; Rhomberg, P.R.; Borroto-Esoda, K.; Castanheira, M. Differential activity of the oral glucan synthase inhibitor SCY-078 against wild-type and echinocandin-resistant strains of Candida species. Antimicrob. Agents Chemother.,  2017, 61(8), 1-9.
[http://dx.doi.org/10.1128/AAC.00161-17] [PMID:  28533234] 
[181] 
Schell, W.A.; Jones, A.M.; Borroto-Esoda, K.; Alexander, B.D. Antifungal activity of SCY-078 and standard antifungal agents against 178 clinical isolates of resistant and susceptible Candida species. Antimicrob. Agents Chemother.,  2017, 61(11), 1-6.
[http://dx.doi.org/10.1128/AAC.01102-17] [PMID:  28827419] 
[182] 
Lamoth, F.; Alexander, B.D. Antifungal activities of SCY-078 (MK-3118) and standard antifungal agents against clinical non-Aspergillus mold isolates. Antimicrob. Agents Chemother.,  2015, 59(7), 4308-4311.
[http://dx.doi.org/10.1128/AAC.00234-15] [PMID:  25896696] 
[183] 
Wiederhold, N.P.; Najvar, L.K.; Jaramillo, R.; Olivo, M.; Pizzini, J.; Catano, G.; Patterson, T.F. Oral glucan synthase inhibitor SCY-078 is effective in an experimental murine model of invasive candidiasis caused by WT and echinocandin-resistant Candida glabrata. J. Antimicrob. Chemother.,  2018, 73(2), 448-451.
[http://dx.doi.org/10.1093/jac/dkx422] [PMID:  29177447] 
[184] 
Lepak, A.J.; Marchillo, K.; Andes, D.R. Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model. Antimicrob. Agents Chemother.,  2015, 59(2), 1265-1272.
[http://dx.doi.org/10.1128/AAC.04445-14] [PMID:  25512406] 
[185] 
Wring, S.A.; Randolph, R.; Park, S.; Abruzzo, G.; Chen, Q.; Flattery, A.; Garrett, G.; Peel, M.; Outcalt, R.; Powell, K.; Trucksis, M.; Angulo, D.; Borroto-Esoda, K. Preclinical pharmacokinetics and pharmacodynamic target of SCY-078, a first-in-class orally active antifungal glucan synthesis inhibitor, in murine models of disseminated candidiasis. Antimicrob. Agents Chemother.,  2017, 61(4), 1-15.
[http://dx.doi.org/10.1128/AAC.02068-16] [PMID:  28137806] 
[186] 
Wring, S.; Murphy, G.; Atiee, G.; Corr, C.; Hyman, M.; Willett, M.; Angulo, D. Lack of impact by SCY-078, a first-in-class oral fungicidal glucan synthase inhibitor, on the pharmacokinetics of rosiglitazone, a substrate for CYP450 2C8, supports the low risk for clinically relevant metabolic drug-drug interactions. J. Clin. Pharmacol.,  2018, 58(10), 1305-1313.
[http://dx.doi.org/10.1002/jcph.1146] [PMID:  29746713] 
[187] 
Wring, S.; Murphy, G.; Atiee, G.; Corr, C.; Hyman, M.; Willett, M.; Angulo, D. Clinical pharmacokinetics and drug-drug interaction potential for coadministered SCY-078, an oral fungicidal glucan synthase inhibitor, and tacrolimus. Clin. Pharmacol. Drug Dev.,  2019, 8(1), 60-69.
[http://dx.doi.org/10.1002/cpdd.588] [PMID:  29947477] 
[188] 
Watanabe, N.A.; Miyazaki, M.; Horii, T.; Sagane, K.; Tsukahara, K.; Hata, K. E1210, a new broad-spectrum antifungal, suppresses Candida albicans hyphal growth through inhibition of glycosylphosphatidylinositol biosynthesis. Antimicrob. Agents Chemother.,  2012, 56(2), 960-971.
[http://dx.doi.org/10.1128/AAC.00731-11] [PMID:  22143530] 
[189] 
Arendrup, M.C.; Chowdhary, A.; Astvad, K.M.T.; Jørgensen, K.M. APX001A in vitro activity against contemporary blood isolates and C. auris determined by the EUCAST reference method. Antimicrob. Agents Chemother.,  2018, 62(10), 1-9.
[http://dx.doi.org/10.1128/AAC.01225-18] [PMID:  30104264] 
[190] 
Hager, C.L.; Larkin, E.L.; Long, L.; Zohra Abidi, F.; Shaw, K.J.; Ghannoum, M.A. In vitro and in vivo evaluation of the antifungal activity of APX001A/APX001 against Candida auris. Antimicrob. Agents Chemother.,  2018, 62(3), 1-7.
[http://dx.doi.org/10.1128/AAC.02319-17] [PMID:  29311065] 
[191] 
Miyazaki, M.; Horii, T.; Hata, K.; Watanabe, N.A.; Nakamoto, K.; Tanaka, K.; Shirotori, S.; Murai, N.; Inoue, S.; Matsukura, M.; Abe, S.; Yoshimatsu, K.; Asada, M. In vitro activity of E1210, a novel antifungal, against clinically important yeasts and molds. Antimicrob. Agents Chemother.,  2011, 55(10), 4652-4658.
[http://dx.doi.org/10.1128/AAC.00291-11] [PMID:  21825291] 
[192] 
Pfaller, M.A.; Duncanson, F.; Messer, S.A.; Moet, G.J.; Jones, R.N.; Castanheira, M. In vitro activity of a novel broad-spectrum antifungal, E1210, tested against Aspergillus spp. determined by CLSI and EUCAST broth microdilution methods. Antimicrob. Agents Chemother.,  2011, 55(11), 5155-5158.
[http://dx.doi.org/10.1128/AAC.00570-11] [PMID:  21844312] 
[193] 
Castanheira, M.; Duncanson, F.P.; Diekema, D.J.; Guarro, J.; Jones, R.N.; Pfaller, M.A. Activities of E1210 and comparator agents tested by CLSI and EUCAST broth microdilution methods against Fusarium and Scedosporium species identified using molecular methods. Antimicrob. Agents Chemother.,  2012, 56(1), 352-357.
[http://dx.doi.org/10.1128/AAC.05414-11] [PMID:  22083469] 
[194] 
Pfaller, M.A.; Hata, K.; Jones, R.N.; Messer, S.A.; Moet, G.J.; Castanheira, M. In vitro activity of a novel broad-spectrum antifungal, E1210, tested against Candida spp. as determined by CLSI broth microdilution method. Diagn. Microbiol. Infect. Dis.,  2011, 71(2), 167-170.
[http://dx.doi.org/10.1016/j.diagmicrobio.2011.05.001] [PMID:  21696907] 
[195] 
Pfaller, M.A.; Watanabe, N.; Castanheira, M.; Messer, S.A.; Jones, R.N. Pre-clinical development of antifungal susceptibility test methods for the testing of the novel antifungal agent E1210 versus Candida: comparison of CLSI and European Committee on Antimicrobial Susceptibility Testing methods. J. Antimicrob. Chemother.,  2011, 66(11), 2581-2584.
[http://dx.doi.org/10.1093/jac/dkr342] [PMID:  21873291] 
[196] 
Shaw, K.J.; Schell, W.A.; Covel, J.; Duboc, G.; Giamberardino, C.; Kapoor, M.; Moloney, M.; Soltow, Q.A.; Tenor, J.L.; Toffaletti, D.L.; Trzoss, M.; Webb, P.; Perfect, J.R. In vitro and in vivo evaluation of APX001A/APX001 and other Gwt1 inhibitors against Cryptococcus. Antimicrob. Agents Chemother.,  2018, 62(8), 1-13.
[http://dx.doi.org/10.1128/AAC.00523-18] [PMID:  29891599] 
[197] 
Zhao, M.; Lepak, A.J.; VanScoy, B.; Bader, J.C.; Marchillo, K.; Vanhecker, J.; Ambrose, P.G.; Andes, D.R. In vivo pharmacokinetics and pharmacodynamics of APX001 against Candida spp. in a neutropenic disseminated candidiasis mouse model. Antimicrob. Agents Chemother.,  2018, 62(4), 1-9.
[http://dx.doi.org/10.1128/AAC.02542-17] [PMID:  29378706] 
[198] 
Hata, K.; Horii, T.; Miyazaki, M.; Watanabe, N.A.; Okubo, M.; Sonoda, J.; Nakamoto, K.; Tanaka, K.; Shirotori, S.; Murai, N.; Inoue, S.; Matsukura, M.; Abe, S.; Yoshimatsu, K.; Asada, M. Efficacy of oral E1210, a new broad-spectrum antifungal with a novel mechanism of action, in murine models of candidiasis, aspergillosis, and fusariosis. Antimicrob. Agents Chemother.,  2011, 55(10), 4543-4551.
[http://dx.doi.org/10.1128/AAC.00366-11] [PMID:  21788462] 
[199] 
Wiederhold, N.P.; Najvar, L.K.; Fothergill, A.W.; McCarthy, D.I.; Bocanegra, R.; Olivo, M.; Kirkpatrick, W.R.; Everson, M.P.; Duncanson, F.P.; Patterson, T.F. The investigational agent E1210 is effective in treatment of experimental invasive candidiasis caused by resistant Candida albicans. Antimicrob. Agents Chemother.,  2015, 59(1), 690-692.
[http://dx.doi.org/10.1128/AAC.03944-14] [PMID:  25331706] 
[200] 
Nishikawa, H.; Yamada, E.; Shibata, T.; Uchihashi, S.; Fan, H.; Hayakawa, H.; Nomura, N.; Mitsuyama, J. Uptake of T-2307, a novel arylamidine, in Candida albicans. J. Antimicrob. Chemother.,  2010, 65(8), 1681-1687.
[http://dx.doi.org/10.1093/jac/dkq177] [PMID:  20513704] 
[201] 
Shibata, T.; Takahashi, T.; Yamada, E.; Kimura, A.; Nishikawa, H.; Hayakawa, H.; Nomura, N.; Mitsuyama, J. T-2307 causes collapse of mitochondrial membrane potential in yeast. Antimicrob. Agents Chemother.,  2012, 56(11), 5892-5897.
[http://dx.doi.org/10.1128/AAC.05954-11] [PMID:  22948882] 
[202] 
Mitsuyama, J.; Nomura, N.; Hashimoto, K.; Yamada, E.; Nishikawa, H.; Kaeriyama, M.; Kimura, A.; Todo, Y.; Narita, H. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine. Antimicrob. Agents Chemother.,  2008, 52(4), 1318-1324.
[http://dx.doi.org/10.1128/AAC.01159-07] [PMID:  18227186] 
[203] 
Moriyama, B.; Gordon, L.A.; McCarthy, M.; Henning, S.A.; Walsh, T.J.; Penzak, S.R. Emerging drugs and vaccines for candidemia. Mycoses,  2014, 57(12), 718-733.
[http://dx.doi.org/10.1111/myc.12265] [PMID:  25294098] 
[204] 
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(3), 692-695.
[http://dx.doi.org/10.1093/jac/dkv398] [PMID:  26620102] 
[205] 
Yamada, E.; Nishikawa, H.; Nomura, N.; Mitsuyama, J. T-2307 shows efficacy in a murine model of Candida glabrata infection despite in vitro trailing growth phenomena. Antimicrob. Agents Chemother.,  2010, 54(9), 3630-3634.
[http://dx.doi.org/10.1128/AAC.00355-10] [PMID:  20547803] 
[206] 
Wiederhold, N.P.; Najvar, L.K.; Fothergill, A.W.; Bocanegra, R.; Olivo, M.; McCarthy, D.I.; Kirkpatrick, W.R.; Fukuda, Y.; Mitsuyama, J.; Patterson, T.F. The novel arylamidine T-2307 maintains in vitro and in vivo activity against echinocandin-resistant Candida albicans. Antimicrob. Agents Chemother.,  2015, 59(2), 1341-1343.
[http://dx.doi.org/10.1128/AAC.04228-14] [PMID:  25451054] 
[207] 
Nishikawa, H.; Fukuda, Y.; Mitsuyama, J.; Tashiro, M.; Tanaka, A.; Takazono, T.; Saijo, T.; Yamamoto, K.; Nakamura, S.; Imamura, Y.; Miyazaki, T.; Kakeya, H.; Yamamoto, Y.; Yanagihara, K.; Mukae, H.; Kohno, S.; Izumikawa, K. 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(6), 1709-1713.
[http://dx.doi.org/10.1093/jac/dkx020] [PMID:  28201509] 
[208] 
Pfaller, M.A.; Messer, S.A.; Georgopapadakou, N.; Martell, L.A.; Besterman, J.M.; Diekema, D.J. Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens. J. Clin. Microbiol.,  2009, 47(12), 3797-3804.
[http://dx.doi.org/10.1128/JCM.00618-09] [PMID:  19794038] 
[209] 
Pfaller, M.A.; Rhomberg, P.R.; Messer, S.A.; Castanheira, M. In vitro activity of a Hos2 deacetylase inhibitor, MGCD290, in combination with echinocandins against echinocandin-resistant Candida species. Diagn. Microbiol. Infect. Dis.,  2015, 81(4), 259-263.
[http://dx.doi.org/10.1016/j.diagmicrobio.2014.11.008] [PMID:  25600842] 
[210] 
Baxter, B.K.; DiDone, L.; Ogu, D.; Schor, S.; Krysan, D.J. Identification, in vitro activity and mode of action of phosphoinositide-dependent-1 kinase inhibitors as antifungal molecules. ACS Chem. Biol.,  2011, 6(5), 502-510.
[http://dx.doi.org/10.1021/cb100399x] [PMID:  21294551] 
[211] 
Koselny, K.; Green, J.; Favazzo, L.; Glazier, V.E.; DiDone, L.; Ransford, S.; Krysan, D.J. Antitumor/antifungal celecoxib derivative AR-12 is a non-nucleoside inhibitor of the ANL-family adnylating enzyme acetyl CoA synthetase. ACS Infect. Dis.,  2016, 2(4), 268-280.
[http://dx.doi.org/10.1021/acsinfecdis.5b00134] [PMID:  27088128] 
[212] 
Kushwaha, A.S.; Sharma, P.; Shivakumar, H.N.; Rappleye, C.; Zukiwski, A.; Proniuk, S.; Murthy, S.N. Trans-ungual delivery of AR-12, a novel antifungal drug. AAPS PharmSciTech,  2017, 18(7), 2702-2705.
[http://dx.doi.org/10.1208/s12249-017-0752-y] [PMID:  28289970] 
[213] 
Nakamura, I.; Ohsumi, K.; Yoshikawa, K.; Kanasaki, R.; Masaki, T.; Takase, S.; Hashimoto, M.; Fujie, A.; Nakai, T.; Matsumoto, S.; Takeda, S.; Akamatsu, S.; Uchida, S.; Maki, K. In ASP2397: A Novel Natural Product with Potent Fungicidal Activity against Aspergillus spp. (1) - A New Mode of Action and In Vitro Activity. Proceedings of the 54th inter science conference on antimicrobial agents and chemotherapy, USA2014.
[214] 
Nakamura, I.; Nakai, T.; Matsumoto, S.; Takeda, S.; Akamatsu, S.; Uchida, S.; Koide, Y.; Mitori, H.; Noto, T.; Maki, K. In ASP2397: A novel natural product with potent fungicidal activity against aspergillus spp. (2) - in vivo activity against A. fumigatus. Proceedings of 54th inter science conference on antimicrobial agents and chemotherapy, USA2014.
[215] 
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. (Tokyo),  2017, 70(1), 45-51.
[http://dx.doi.org/10.1038/ja.2016.107] [PMID:  27599768] 
[216] 
Walsh, C.T.; Fischbach, M.A. Repurposing libraries of eukaryotic protein kinase inhibitors for antibiotic discovery. Proc. Natl. Acad. Sci. USA,  2009, 106(6), 1689-1690.
[http://dx.doi.org/10.1073/pnas.0813405106] [PMID:  19193851] 
[217] 
Knight, Z.A.; Shokat, K.M. Features of selective kinase inhibitors. Chem. Biol.,  2005, 12(6), 621-637.
[http://dx.doi.org/10.1016/j.chembiol.2005.04.011] [PMID:  15975507] 
[218] 
Colley, T.; Sehra, G.; Chowdhary, A.; Alanio, A.; Kelly, S.L.; Kizawa, Y.; Armstrong-James, D.; Fisher, M.C.; Warrilow, A.G.S.; Parker, J.E.; Kelly, D.E.; Kimura, G.; Nishimoto, Y.; Sunose, M.; Onions, S.; Crepin, D.; Lagasse, F.; Crittall, M.; Shannon, J.; McConville, M.; King-Underwood, J.; Naylor, A.; Bretagne, S.; Murray, J.; Ito, K.; Strong, P.; Rapeport, G. In vitro and in vivo efficacy of a novel and long acting fungicidal azole, PC1244 on Aspergillus fumigatus infection. Antimicrob. Agents Chemother.,  2018, 62(5), 1-14.
[http://dx.doi.org/10.1128/AAC.01941-17] [PMID:  29439966] 
[219] 
Colley, T.; Alanio, A.; Kelly, S.L.; Sehra, G.; Kizawa, Y.; Warrilow, A.G.S.; Parker, J.E.; Kelly, D.E.; Kimura, G.; Anderson-Dring, L.; Nakaoki, T.; Sunose, M.; Onions, S.; Crepin, D.; Lagasse, F.; Crittall, M.; Shannon, J.; Cooke, M.; Bretagne, S.; King-Underwood, J.; Murray, J.; Ito, K.; Strong, P.; Rapeport, G. In vitro and in vivo antifungal profile of a novel and long-acting inhaled azole, PC945, on Aspergillus fumigatus infection. Antimicrob. Agents Chemother.,  2017, 61(5), 1-18.
[http://dx.doi.org/10.1128/AAC.02280-16] [PMID:  28223388] 
[220] 
Kimura, G.; Nakaoki, T.; Colley, T.; Rapeport, G.; Strong, P.; Ito, K.; Kizawa, Y. In vivo biomarker analysis of the effects of intranasally dosed PC945, a novel antifungal triazole, on Aspergillus fumigatus infection in immunocompromised mice. Antimicrob. Agents Chemother.,  2017, 61(9), 1-13.
[http://dx.doi.org/10.1128/AAC.00124-17] [PMID:  28630185] 
[221] 
Gómez-García, O.; Andrade-Pavón, D.; Campos-Aldrete, E.; Ballinas-Indilí, R.; Méndez-Tenorio, A.; Villa-Tanaca, L.; Álvarez-Toledano, C. Synthesis, molecular docking, and antimycotic evaluation of some 3-acyl imidazo[1,2-a]pyrimidines. Molecules,  2018, 23(3), 599.
[http://dx.doi.org/10.3390/molecules23030599] [PMID:  29518930] 
[222] 
Mircus, G.; Albert, N.; Ben-Yaakov, D.; Chikvashvili, D.; Shadkchan, Y.; Kontoyiannis, D.P.; Osherov, N. Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) that interfere with fungal protein synthesis. Antimicrob. Agents Chemother.,  2015, 59(9), 5631-5640.
[http://dx.doi.org/10.1128/AAC.00850-15] [PMID:  26149982] 
[223] 
Rollin-Pinheiro, R.; Singh, A.; Barreto-Bergter, E.; Del Poeta, M. Sphingolipids as targets for treatment of fungal infections. Future Med. Chem.,  2016, 8(12), 1469-1484.
[http://dx.doi.org/10.4155/fmc-2016-0053] [PMID:  27502288] 
[224] 
Mor, V.; Rella, A.; Farnoud, A.M.; Singh, A.; Munshi, M.; Bryan, A.; Naseem, S.; Konopka, J.B.; Ojima, I.; Bullesbach, E.; Ashbaugh, A.; Linke, M.J.; Cushion, M.; Collins, M.; Ananthula, H.K.; Sallans, L.; Desai, P.B.; Wiederhold, N.P.; Fothergill, A.W.; Kirkpatrick, W.R.; Patterson, T.; Wong, L.H.; Sinha, S.; Giaever, G.; Nislow, C.; Flaherty, P.; Pan, X.; Cesar, G.V.; de Melo Tavares, P.; Frases, S.; Miranda, K.; Rodrigues, M.L.; Luberto, C.; Nimrichter, L.; Del Poeta, M. Identification of a new class of antifungals targeting the synthesis of fungal sphingolipids. MBio,  2015, 6(3)e00647
[http://dx.doi.org/10.1128/mBio.00647-15] [PMID:  26106079] 
[225] 
Ramírez-Villalva, A.; González-Calderón, D.; Rojas-García, R.I.; González-Romero, C.; Tamaríz-Mascarúa, J.; Morales-Rodríguez, M.; Zavala-Segovia, N.; Fuentes-Benítes, A. Synthesis and antifungal activity of novel oxazolidin-2-one-linked 1,2,3-triazole derivatives. MedChemComm,  2017, 8(12), 2258-2262.
[http://dx.doi.org/10.1039/C7MD00442G] [PMID:  30108741] 
[226] 
Wall, G.; Chaturvedi, A.K.; Wormley, F.L., Jr; Wiederhold, N.P.; Patterson, H.P.; Patterson, T.F.; Lopez-Ribot, J.L. Screening a repurposing library for inhibitors of multi-drug resistant Candida auris identifies ebselen as a repositionable candidate for antifungal drug development. Antimicrob. Agents Chemother.,  2018, 62(10), 1-13.
[http://dx.doi.org/10.1128/AAC.01084-18] [PMID:  30104269] 
[227] 
Hashemi, M.M.; Rovig, J.; Holden, B.S.; Taylor, M.F.; Weber, S.; Wilson, J.; Hilton, B.; Zaugg, A.L.; Ellis, S.W.; Yost, C.D.; Finnegan, P.M.; Kistler, C.K.; Berkow, E.L.; Deng, S.; Lockhart, S.R.; Peterson, M.; Savage, P.B. Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm forms. J. Antimicrob. Chemother.,  2018, 73(6), 1537-1545.
[http://dx.doi.org/10.1093/jac/dky085] [PMID:  29635279] 
[228] 
Durnaś, B.; Wnorowska, U.; Pogoda, K.; Deptuła, P.; Wątek, M.; Piktel, E.; Głuszek, S.; Gu, X.; Savage, P.B.; Niemirowicz, K.; Bucki, R. Candidacidal activity of selected ceragenins and human cathelicidin LL-37 in experimental settings mimicking infection sites. PLoS One,  2016, 11(6)e0157242
[http://dx.doi.org/10.1371/journal.pone.0157242] [PMID:  27315208] 
[229] 
Yu, S-J.; Chang, Y-L.; Chen, Y-L. Calcineurin signaling: lessons from Candida species. FEMS Yeast Res.,  2015, 15(4)fov016
[http://dx.doi.org/10.1093/femsyr/fov016] [PMID:  25878052] 
[230] 
Tome, M.; Zupan, J.; Tomicic, Z.; Matos, T.; Raspor, P. Synergistic and antagonistic effects of immunomodulatory drugs on the action of antifungals against Candida glabrata and Saccharomyces cerevisiae. PeerJ,  2018, 6, 1-23.
[http://dx.doi.org/10.7717/peerj.4999] 
[231] 
Chen, Y.L.; Lehman, V.N.; Averette, A.F.; Perfect, J.R.; Heitman, J. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans. PLoS One,  2013, 8(3)e57672
[http://dx.doi.org/10.1371/journal.pone.0057672] [PMID:  23472097] 
[232] 
Li, H.; Chen, Z.; Zhang, C.; Gao, Y.; Zhang, X.; Sun, S. Resistance reversal induced by a combination of fluconazole and tacrolimus (FK506) in Candida glabrata. J. Med. Microbiol.,  2015, 64(Pt 1), 44-52.
[http://dx.doi.org/10.1099/jmm.0.081760-0] [PMID:  25355935] 
[233] 
Denardi, L.B.; Mario, D.A.; Loreto, E.S.; Santurio, J.M.; Alves, S.H. Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole-susceptible and fluconazole-resistant Candida glabrata isolates. Braz. J. Microbiol.,  2015, 46(1), 125-129.
[http://dx.doi.org/10.1590/S1517-838246120120442] [PMID:  26221097] 
[234] 
Robbins, N.; Spitzer, M.; Yu, T.; Cerone, R.P.; Averette, A.K.; Bahn, Y-S.; Heitman, J.; Sheppard, D.C.; Tyers, M.; Wright, G.D. An antifungal combination matrix identifies a rich pool of adjuvant molecules that enhance drug activity against diverse fungal pathogens. Cell Rep.,  2015, 13(7), 1481-1492.
[http://dx.doi.org/10.1016/j.celrep.2015.10.018] [PMID:  26549450] 
[235] 
Harizi, H.; Corcuff, J.B.; Gualde, N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends Mol. Med.,  2008, 14(10), 461-469.
[http://dx.doi.org/10.1016/j.molmed.2008.08.005] [PMID:  18774339] 
[236] 
Noverr, M.C.; Phare, S.M.; Toews, G.B.; Coffey, M.J.; Huffnagle, G.B. Pathogenic yeasts Cryptococcus neoformans and Candida albicans produce immunomodulatory prostaglandins. Infect. Immun.,  2001, 69(5), 2957-2963.
[http://dx.doi.org/10.1128/IAI.69.5.2957-2963.2001] [PMID:  11292712] 
[237] 
Liu, X.; Li, T.; Wang, D.; Yang, Y.; Sun, W.; Liu, J.; Sun, S. Synergistic antifungal effect of fluconazole combined with licofelone against resistant Candida albicans. Front. Microbiol.,  2017, 8, 2101.
[http://dx.doi.org/10.3389/fmicb.2017.02101] [PMID:  29163396] 
[238] 
Zhai, B.; Zhou, H.; Yang, L.; Zhang, J.; Jung, K.; Giam, C-Z.; Xiang, X.; Lin, X. Polymyxin B, in combination with fluconazole, exerts a potent fungicidal effect. J. Antimicrob. Chemother.,  2010, 65(5), 931-938.
[http://dx.doi.org/10.1093/jac/dkq046] [PMID:  20167587] 
[239] 
Pankey, G.; Ashcraft, D.; Kahn, H.; Ismail, A. Time-kill assay and Etest evaluation for synergy with polymyxin B and fluconazole against Candida glabrata. Antimicrob. Agents Chemother.,  2014, 58(10), 5795-5800.
[http://dx.doi.org/10.1128/AAC.03035-14] [PMID:  25049251] 
[240] 
Fiori, A.; Van Dijck, P. Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis. Antimicrob. Agents Chemother.,  2012, 56(7), 3785-3796.
[http://dx.doi.org/10.1128/AAC.06017-11] [PMID:  22564841] 
[241] 
Hooper, R.W.; Ashcraft, D.S.; Pankey, G.A. In vitro synergy with fluconazole plus doxycycline or tigecycline against clinical Candida glabrata isolates. Med. Mycol.,  2019, 57(1), 122-126.
[http://dx.doi.org/10.1093/mmy/myy008] [PMID:  29618039] 
[242] 
Koselny, K.; Green, J.; DiDone, L.; Halterman, J.P.; Fothergill, A.W.; Wiederhold, N.P.; Patterson, T.F.; Cushion, M.T.; Rappelye, C.; Wellington, M.; Krysan, D.J. The celecoxib derivative AR-12 has broad-spectrum antifungal activity in vitro and improves the activity of fluconazole in a murine model of Cryptococcosis. Antimicrob. Agents Chemother.,  2016, 60(12), 7115-7127.
[http://dx.doi.org/10.1128/AAC.01061-16] [PMID:  27645246] 
Rights & Permissions Print Cite
Article Metrics
65
1
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1568026619666191025152412	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

New and Promising Chemotherapeutics for Emerging Infections Involving Drug-resistant Non-albicans Candida Species

Abstract

Graphical Abstract

Chemistry Based on Natural Products for Therapeutic Purposes

Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design

Drug Discovery in the Age of Artificial Intelligence

From Biodiversity to Chemical Diversity: Focus of Flavonoids

Current Topics in Medicinal Chemistry

New and Promising Chemotherapeutics for Emerging Infections Involving Drug-resistant Non-albicans Candida Species

Abstract

Graphical Abstract

Call for Papers in Thematic Issues

Chemistry Based on Natural Products for Therapeutic Purposes

Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design

Drug Discovery in the Age of Artificial Intelligence

From Biodiversity to Chemical Diversity: Focus of Flavonoids

Related Journals

Related Books

Related Articles
