Novel Therapeutic Approaches to Invasive Candidiasis: Considerations for the Clinician

References

• Lamoth F, Lockhart SR, Berkow EL, Calandra T. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother. 2018;73:i4–i13. doi:10.1093/jac/dkx444
   PubMed Web of Science ®Google Scholar
• Pappas PG, Kauffman CA, Andes DR, et al. Clinical Practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62:e1–e50. doi:10.1093/cid/civ933
   PubMed Web of Science ®Google Scholar
• Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302:2323–2329. doi:10.1001/jama.2009.1754
   PubMed Web of Science ®Google Scholar
• Lamoth F, Kontoyiannis DP. The Candida auris alert: facts and perspectives. J Infect Dis. 2018;217:516–520. doi:10.1093/infdis/jix597
   PubMed Web of Science ®Google Scholar
• Koehler P, Stecher M, Cornely OA, et al. Morbidity and mortality of candidaemia in Europe: an epidemiologic meta-analysis. Clin Microbiol Infect. 2019;25:1200–1212. doi:10.1016/j.cmi.2019.04.024
   PubMed Web of Science ®Google Scholar
• Tsay SV, Mu Y, Williams S, et al. Burden of Candidemia in the United States, 2017. Clin Infect Dis. 2020;71:e449–e453. doi:10.1093/cid/ciaa193
   PubMed Web of Science ®Google Scholar
• Battistolo J, Glampedakis E, Damonti L, et al. Increasing morbidity and mortality of candidemia over one decade in a Swiss university hospital. Mycoses. 2021;64(12):1512–1520. doi:10.1111/myc.13376
   PubMed Web of Science ®Google Scholar
• Boan P, Gardam D. Epidemiology and antifungal susceptibility patterns of candidemia from a tertiary centre in Western Australia. J Chemother. 2019;31:137–140. doi:10.1080/1120009X.2019.1595895
   PubMed Web of Science ®Google Scholar
• Verma R, Pradhan D, Hasan Z, Singh H, Jain AK, Khan LA. A systematic review on distribution and antifungal resistance pattern of Candida species in the Indian population. Med Mycol. 2021;59:1145–1165. doi:10.1093/mmy/myab058
   PubMed Web of Science ®Google Scholar
• Xiao M, Chen SC, Kong F, et al. Distribution and antifungal susceptibility of Candida species causing candidemia in China: an update from the CHIF-NET study. J Infect Dis. 2020;221:S139–S147. doi:10.1093/infdis/jiz573
   PubMed Web of Science ®Google Scholar
• Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug-resistant candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:134–140. doi:10.1093/cid/ciw691
   PubMed Web of Science ®Google Scholar
• Ruiz-Gaitan A, Moret AM, Tasias-Pitarch M, et al. An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital. Mycoses. 2018;61:498–505. doi:10.1111/myc.12781
   PubMed Web of Science ®Google Scholar
• Schelenz S, Hagen F, Rhodes JL, et al. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:35. doi:10.1186/s13756-016-0132-5
   PubMed Web of Science ®Google Scholar
• Chowdhary A, Prakash A, Sharma C, et al. 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;73:891–899. doi:10.1093/jac/dkx480
   PubMed Web of Science ®Google Scholar
• Kilburn S, Innes G, Quinn M, et al. Antifungal resistance trends of candida auris clinical isolates in New York and New Jersey from 2016 to 2020. Antimicrob Agents Chemother. 2022;66:e0224221. doi:10.1128/aac.02242-21
   PubMed Web of Science ®Google Scholar
• Rudramurthy SM, Chakrabarti A, Paul RA, et al. Candida auris candidaemia in Indian ICUs: analysis of risk factors. J Antimicrob Chemother. 2017;72:1794–1801. doi:10.1093/jac/dkx034
   PubMed Web of Science ®Google Scholar
• van Schalkwyk E, Mpembe RS, Thomas J, et al. Epidemiologic shift in candidemia driven by Candida auris, South Africa, 2016-2017(1). Emerg Infect Dis. 2019;25:1698–1707. doi:10.3201/eid2509.190040
   PubMed Web of Science ®Google Scholar
• Cornely OA, Bassetti M, Calandra T, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18(Suppl 7):19–37. doi:10.1111/1469-0691.12039
   PubMed Web of Science ®Google Scholar
• Ullmann AJ, Akova M, Herbrecht R, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: adults with haematological malignancies and after haematopoietic stem cell transplantation (HCT). Clin Microbiol Infect. 2012;18(Suppl 7):53–67. doi:10.1111/1469-0691.12041
   PubMed Web of Science ®Google Scholar
• Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope WW. Breakpoints for antifungal agents: an update from EUCAST focussing on echinocandins against Candida spp. and triazoles against Aspergillus spp. Drug Resist Updat. 2013;16:81–95. doi:10.1016/j.drup.2014.01.001
   PubMed Web of Science ®Google Scholar
• Fernandez-Ruiz M, Aguado JM, Almirante B, et al. Initial use of echinocandins does not negatively influence outcome in Candida parapsilosis bloodstream infection: a propensity score analysis. Clin Infect Dis. 2014;58:1413–1421. doi:10.1093/cid/ciu158
   PubMed Web of Science ®Google Scholar
• Alexander BD, Johnson MD, Pfeiffer CD, et al. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56:1724–1732. doi:10.1093/cid/cit136
   PubMed Web of Science ®Google Scholar
• Astvad KMT, Johansen HK, Roder BL, et al. Update from a 12-year nationwide fungemia surveillance: increasing intrinsic and acquired resistance causes concern. J Clin Microbiol. 2018;56:e01564–17. doi:10.1128/JCM.01564-17
   PubMed Web of Science ®Google Scholar
• Beyda ND, John J, Kilic A, Alam MJ, Lasco TM, Garey KW. FKS mutant Candida glabrata: risk factors and outcomes in patients with candidemia. Clin Infect Dis. 2014;59:819–825. doi:10.1093/cid/ciu407
   PubMed Web of Science ®Google Scholar
• Kritikos A, Neofytos D, Khanna N, et al. Accuracy of Sensititre YeastOne echinocandins epidemiological cut-off values for identification of FKS mutant Candida albicans and Candida glabrata: a ten year national survey of the Fungal Infection Network of Switzerland (FUNGINOS). Clin Microbiol Infect. 2018;24:1214e1–1214 e4. doi:10.1016/j.cmi.2018.05.012
   Web of Science ®Google Scholar
• Mamali V, Siopi M, Charpantidis S, et al. Increasing incidence and shifting epidemiology of candidemia in Greece: results from the first nationwide 10-year survey. J Fungi. 2022;8(2):116. doi:10.3390/jof8020116
   Web of Science ®Google Scholar
• Shields RK, Nguyen MH, Press EG, et al. Rate of FKS mutations among consecutive candida isolates causing bloodstream infection. Antimicrob Agents Chemother. 2015;59:7465–7470. doi:10.1128/AAC.01973-15
   PubMed Web of Science ®Google Scholar
• Ahmad S, Khan Z, Al-Sweih N, Alfouzan W, Joseph L. Candida auris in various hospitals across Kuwait and their susceptibility and molecular basis of resistance to antifungal drugs. Mycoses. 2020;63:104–112. doi:10.1111/myc.13022
   PubMed Web of Science ®Google Scholar
• Maphanga TG, Naicker SD, Kwenda S, et al. In vitro antifungal resistance of candida auris isolates from bloodstream infections, South Africa. Antimicrob Agents Chemother. 2021;65:e0051721. doi:10.1128/AAC.00517-21
   PubMed Web of Science ®Google Scholar
• Coste AT, Kritikos A, Li J, et al. Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland. Infection. 2020;48:761–766. doi:10.1007/s15010-020-01475-8
   PubMed Web of Science ®Google Scholar
• McCarthy MW, Kontoyiannis DP, Cornely OA, Perfect JR, Walsh TJ. Novel agents and drug targets to meet the challenges of resistant fungi. J Infect Dis. 2017;216:S474–S483. doi:10.1093/infdis/jix130
   PubMed Web of Science ®Google Scholar
• Zhao Y, Perlin DS. Review of the novel echinocandin antifungal rezafungin: animal studies and clinical data. J Fungi. 2020;6:192. doi:10.3390/jof6040192
   Web of Science ®Google Scholar
• Arendrup MC, Meletiadis J, Zaragoza O, et al. Multicentre determination of rezafungin (CD101) susceptibility of Candida species by the EUCAST method. Clin Microbiol Infect. 2018;24:1200–1204. doi:10.1016/j.cmi.2018.02.021
   PubMed Web of Science ®Google Scholar
• Helleberg M, Jorgensen KM, Hare RK, Datcu R, Chowdhary A, Arendrup MC. Rezafungin in vitro activity against contemporary Nordic clinical candida isolates and candida auris determined by the eucast reference method. Antimicrob Agents Chemother. 2020;64:e02438–19. doi:10.1128/AAC.02438-19
   PubMed Web of Science ®Google Scholar
• Hager CL, Larkin EL, Long LA, Ghannoum MA. 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;73:2085–2088. doi:10.1093/jac/dky153
   PubMed Web of Science ®Google Scholar
• Lepak AJ, Zhao M, Andes DR. Pharmacodynamic Evaluation of Rezafungin (CD101) against Candida auris in the Neutropenic Mouse Invasive Candidiasis Model. Antimicrob Agents Chemother. 2018;62:e01572–18. doi:10.1128/AAC.01572-18
   PubMed Web of Science ®Google Scholar
• Lepak AJ, Zhao M, Andes DR. Determination of pharmacodynamic target exposures for rezafungin against Candida tropicalis and Candida dubliniensis in the neutropenic mouse disseminated candidiasis model. Antimicrob Agents Chemother. 2019;63:e01556–19. doi:10.1128/AAC.01556-19
   PubMed Web of Science ®Google Scholar
• Lepak AJ, Zhao M, VanScoy B, Ambrose PG, Andes DR. Pharmacodynamics of a long-acting echinocandin, CD101, in a neutropenic invasive-candidiasis murine model using an extended-interval dosing design. Antimicrob Agents Chemother. 2018;62:e02154–17. doi:10.1128/AAC.02154-17
   PubMed Web of Science ®Google Scholar
• Zhao Y, Perez WB, Jimenez-Ortigosa C, et al. CD101: a novel long-acting echinocandin. Cell Microbiol. 2016;18:1308–1316. doi:10.1111/cmi.12640
   PubMed Web of Science ®Google Scholar
• Zhao Y, Prideaux B, Nagasaki Y, et al. Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. Antimicrob Agents Chemother. 2017;61:e01009–17. doi:10.1128/AAC.01009-17
   PubMed Web of Science ®Google Scholar
• Thompson GR, Soriano A, Skoutelis A, et al. Rezafungin versus caspofungin in a Phase 2, randomized, double-blind study for the treatment of candidemia and invasive candidiasis- the STRIVE trial. Clin Infect Dis. 2021;73:e3647–e3655. doi:10.1093/cid/ciaa1380
   PubMed Web of Science ®Google Scholar
• Thompson III GR, Soriano A, Cornely OA, et al. ReSTORE: efficacy and safety results of the Phase 3, noninferiority trial of rezafungin in the treatment of candidemia and/or invasive candidiasis (IC). ECCMID 23-26 April 2022; Poster #L0244; Lisbon, Portugal; 2022.
   Google Scholar
• Jallow S, Govender NP. Ibrexafungerp: a First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor. J Fungi. 2021;7:163. doi:10.3390/jof7030163
   Web of Science ®Google Scholar
• Pfaller MA, Messer SA, Rhomberg PR, 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:e00161–17. doi:10.1128/AAC.00161-17
   PubMed Web of Science ®Google Scholar
• Arendrup MC, Jorgensen KM, Hare RK, Chowdhary A. In vitro activity of ibrexafungerp (SCY-078) against Candida auris isolates as determined by EUCAST methodology and comparison with activity against C. albicans and C. glabrata and with the activities of six comparator agents. Antimicrob Agents Chemother. 2020;64:e02136–19. doi:10.1128/AAC.02136-19
   PubMed Web of Science ®Google Scholar
• Berkow EL, Angulo D, Lockhart SR. In vitro activity of a novel glucan synthase inhibitor, SCY-078, against Clinical Isolates of Candida auris. Antimicrob Agents Chemother. 2017;61:e00435–17. doi:10.1016/0005-2728(75)90129-2
   PubMed Web of Science ®Google Scholar
• Zhu YC, Barat SA, Borroto-Esoda K, Angulo D, Chaturvedi S, Chaturvedi V. Pan-resistant Candida auris isolates from the outbreak in New York are susceptible to ibrexafungerp (a glucan synthase inhibitor). Int J Antimicrob Agents. 2020;55:105922. doi:10.1016/j.ijantimicag.2020.105922
   PubMed Web of Science ®Google Scholar
• Lepak AJ, Marchillo K, Andes DR. 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;59:1265–1272. doi:10.1128/AAC.04445-14
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Jaramillo R, et al. 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;73:448–451. doi:10.1093/jac/dkx422
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Olivo M, et al. Ibrexafungerp demonstrates in vitro activity against fluconazole-resistant Candida auris and in vivo efficacy with delayed initiation of therapy in an experimental model of invasive candidiasis. Antimicrob Agents Chemother. 2021;65:e02694–20. doi:10.1016/0005-2760(75)90159-9
   PubMed Web of Science ®Google Scholar
• Lee A, Prideaux B, Zimmerman M, et al. Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model. Antimicrob Agents Chemother. 2020;64:e02268–19. doi:10.1128/AAC.02268-19
   PubMed Web of Science ®Google Scholar
• Schwebke JR, Sobel R, Gersten JK, et al. Ibrexafungerp versus placebo for vulvovaginal candidiasis treatment: a phase 3, randomized, controlled superiority trial (VANISH 303). Clin Infect Dis. 2022;74:1979–1985. doi:10.1093/cid/ciab750
   PubMed Web of Science ®Google Scholar
• Sobel R, Nyirjesy P, Ghannoum MA, et al. Efficacy and safety of oral ibrexafungerp for the treatment of acute vulvovaginal candidiasis: a global phase 3, randomised, placebo-controlled superiority study (VANISH 306). BJOG. 2022;129:412–420. doi:10.1111/1471-0528.16972
   PubMed Web of Science ®Google Scholar
• Spec A, Pullman J, Thompson GR, et al. MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis. J Antimicrob Chemother. 2019;74:3056–3062. doi:10.1093/jac/dkz277
   PubMed Web of Science ®Google Scholar
• Wring SA, Randolph R, Park S, et al. 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:e02068–16. doi:10.1128/AAC.02068-16
   PubMed Web of Science ®Google Scholar
• Lamoth F, Lewis RE, Kontoyiannis DP. Investigational antifungal agents for invasive mycoses: a clinical perspective. Clin Infect Dis. 2022;75:534–544. doi:10.1093/cid/ciab1070
   PubMed Web of Science ®Google Scholar
• Shaw KJ, Ibrahim AS. Fosmanogepix: a review of the first-in-class broad spectrum agent for the treatment of invasive fungal infections. J Fungi. 2020;6:239. doi:10.3390/jof6040239
   Web of Science ®Google Scholar
• Watanabe NA, 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;56:960–971. doi:10.1128/AAC.00731-11
   PubMed Web of Science ®Google Scholar
• McLellan CA, Whitesell L, King OD, Lancaster AK, Mazitschek R, Lindquist S. Inhibiting GPI anchor biosynthesis in fungi stresses the endoplasmic reticulum and enhances immunogenicity. ACS Chem Biol. 2012;7:1520–1528. doi:10.1021/cb300235m
   PubMed Web of Science ®Google Scholar
• Arendrup MC, Chowdhary A, Astvad KMT, Jorgensen KM. APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris Determined by the EUCAST Reference Method. Antimicrob Agents Chemother. 2018;62:e01225–18. doi:10.1128/AAC.01225-18
   PubMed Web of Science ®Google Scholar
• Arendrup MC, Chowdhary A, Jorgensen KM, Meletiadis J. Manogepix (APX001A) in vitro activity against candida auris: head-to-head comparison of EUCAST and CLSI MICs. Antimicrob Agents Chemother. 2020;64:e00656–20. doi:10.1128/AAC.00656-20
   PubMed Web of Science ®Google Scholar
• Arendrup MC, Jorgensen KM. Manogepix (APX001A) displays potent in vitro activity against human pathogenic yeast, but with an unexpected correlation to fluconazole MICs. Antimicrob Agents Chemother. 2020;64:e00429–20. doi:10.1128/AAC.00429-20
   PubMed Web of Science ®Google Scholar
• Pfaller MA, Huband MD, Flamm RK, Bien PA, Castanheira M. In vitro activity of APX001A (Manogepix) and comparator agents against 1706 fungal isolates collected during an international surveillance program in 2017. Antimicrob Agents Chemother. 2019;63:e00840–19. doi:10.1128/AAC.00840-19
   PubMed Web of Science ®Google Scholar
• Zhu Y, Kilburn S, Kapoor M, Chaturvedi S, Shaw KJ, Chaturvedi V. In vitro activity of manogepix against multidrug-resistant and panresistant candida auris from the New York Outbreak. Antimicrob Agents Chemother. 2020;64:e01124–20. doi:10.1128/AAC.01124-20
   PubMed Web of Science ®Google Scholar
• Berkow EL, Lockhart SR. Activity of novel antifungal compound APX001A against a large collection of Candida auris. J Antimicrob Chemother. 2018;73:3060–3062. doi:10.1093/jac/dky302
   PubMed Web of Science ®Google Scholar
• Kapoor M, Moloney M, Soltow QA, Pillar CM, Shaw KJ. Evaluation of resistance development to the Gwt1 inhibitor manogepix (APX001A) in Candida species. Antimicrob Agents Chemother. 2019;64:e01387–19. doi:10.1128/AAC.01387-19
   PubMed Web of Science ®Google Scholar
• Liston SD, Whitesell L, Kapoor M, Shaw KJ, Cowen LE. Enhanced efflux pump expression in Candida Mutants results in decreased manogepix susceptibility. Antimicrob Agents Chemother. 2020;64:e00261–20. doi:10.1128/AAC.00261-20
   PubMed Web of Science ®Google Scholar
• Zhao Y, Lee MH, Paderu P, et al. Significantly improved pharmacokinetics enhances in vivo efficacy of APX001 against Echinocandin- and multidrug-resistant Candida isolates in a mouse model of invasive candidiasis. Antimicrob Agents Chemother. 2018;62:e00425–18. doi:10.1128/AAC.00425-18
   PubMed Web of Science ®Google Scholar
• Zhao M, Lepak AJ, VanScoy B, et al. In vivo pharmacokinetics and Pharmacodynamics of APX001 against Candida spp. in a neutropenic disseminated candidiasis mouse model. Antimicrob Agents Chemother. 2018;62:e02542–17. doi:10.1128/AAC.02542-17
   PubMed Web of Science ®Google Scholar
• Hata K, Horii T, Miyazaki M, et al. 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;55:4543–4551. doi:10.1128/AAC.00366-11
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Fothergill AW, et al. The investigational agent E1210 is effective in treatment of experimental invasive candidiasis caused by resistant Candida albicans. Antimicrob Agents Chemother. 2015;59:690–692. doi:10.1128/AAC.03944-14
   PubMed Web of Science ®Google Scholar
• Hager CL, Larkin EL, Long L, Zohra Abidi F, Shaw KJ, Ghannoum MA. In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris. Antimicrob Agents Chemother. 2018;62:e02319–17. doi:10.1128/AAC.02319-17
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Shaw KJ, et al. Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of Candida auris Invasive Candidiasis. Antimicrob Agents Chemother. 2019;63:e01120–19. doi:10.1128/AAC.01120-19
   PubMed Web of Science ®Google Scholar
• Lee A, Wang N, Carter CL, et al. Therapeutic potential of fosmanogepix (APX001) for Intra-abdominal Candidiasis: from lesion penetration to efficacy in a mouse model. Antimicrob Agents Chemother. 2021;65:e02476–20. doi:10.1128/AAC.02476-20
   PubMed Web of Science ®Google Scholar
• Petraitiene R, Petraitis V, Maung BBW, et al. Efficacy and pharmacokinetics of fosmanogepix (APX001) in the treatment of Candida Endophthalmitis and hematogenous meningoencephalitis in nonneutropenic rabbits. Antimicrob Agents Chemother. 2021;65:e01795–20. doi:10.1128/AAC.01795-20
   PubMed Web of Science ®Google Scholar
• Pappas PG, Kullberg BJ, Vazquez JA, et al. Clinical safety and efficacy of novel antifungal, fosmanogepix, in the treatment of candidemia: results from a phase 2 proof of concept trial. Open Forum Infect Dis. 2020;7(Suppl 1). doi:10.1093/ofid/ofaa439.457
   Google Scholar
• Warrilow AG, Hull CM, Parker JE, et al. 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;58:7121–7127. doi:10.1128/AAC.03707-14
   PubMed Web of Science ®Google Scholar
• Warrilow AG, Parker JE, Price CL, et al. 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;60:4530–4538. doi:10.1128/AAC.00349-16
   PubMed Web of Science ®Google Scholar
• Nishimoto AT, Whaley SG, Wiederhold NP, et al. Impact of the major candida glabrata triazole resistance determinants on the activity of the novel investigational tetrazoles VT-1598 and VT-1161. Antimicrob Agents Chemother. 2019;63:e01304–19. doi:10.1128/AAC.01304-19
   PubMed Web of Science ®Google Scholar
• Nishimoto AT, Wiederhold NP, Flowers SA, et al. In vitro activities of the novel investigational tetrazoles VT-1161 and VT-1598 compared to the triazole antifungals against azole-resistant strains and clinical isolates of Candida albicans. Antimicrob Agents Chemother. 2019;63:e00341–19. doi:10.1128/AAC.00341-19
   PubMed Web of Science ®Google Scholar
• Schell WA, Jones AM, Garvey EP, Hoekstra WJ, Schotzinger RJ, Alexander BD. Fungal CYP51 inhibitors VT-1161 and VT-1129 exhibit strong in vitro activity against candida glabrata and C. krusei isolates clinically resistant to azole and echinocandin antifungal compounds. Antimicrob Agents Chemother. 2017;61:e01817–16. doi:10.1128/AAC.01817-16
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Lockhart SR, Najvar LK, et al. The fungal Cyp51-specific inhibitor VT-1598 demonstrates in vitro and in vivo activity against Candida auris. Antimicrob Agents Chemother. 2019;63:e02233–18. doi:10.1128/AAC.02233-18
   PubMed Web of Science ®Google Scholar
• Brand SR, Degenhardt TP, Person K, et al. A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of orally administered VT-1161 in the treatment of recurrent vulvovaginal candidiasis. Am J Obstet Gynecol. 2018;218:624e1–624 e9. doi:10.1016/j.ajog.2018.03.001
   Web of Science ®Google Scholar
• Brand SR, Sobel JD, Nyirjesy P, et al. 2 Study of VT-1161 for the treatment of acute vulvovaginal candidiasis. Clin Infect Dis. 2021;73:e1518–e1524. doi:10.1093/cid/ciaa1204
   PubMed Web of Science ®Google Scholar
• Martens MG, Maximos B, Degenhardt T, et al. Phase 3 study evaluating the safety and efficacy of oteseconazole in the treatment of recurrent vulvovaginal candidiasis and acute vulvovaginal candidiasis infections. Am J Obstet Gynecol. 2022;227(6):880e1–880 e11. doi:10.1016/j.ajog.2022.07.023
   Web of Science ®Google Scholar
• Fakhim H, Emami S, Vaezi A, et al. In Vitro Activities of Novel Azole Compounds ATTAF-1 and ATTAF-2 against Fluconazole-Susceptible and -Resistant Isolates of Candida Species. Antimicrob Agents Chemother. 2017;61:e01106–16. doi:10.1128/AAC.01106-16
   PubMed Web of Science ®Google Scholar
• Motahari K, Badali H, Hashemi SM, et al. Discovery of benzylthio analogs of fluconazole as potent antifungal agents. Future Med Chem. 2018;10:987–1002. doi:10.4155/fmc-2017-0295
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Fothergill AW, et al. The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against echinocandin-resistant Candida glabrata. J Antimicrob Chemother. 2016;71:692–695. doi:10.1093/jac/dkv398
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Fothergill AW, et al. The novel arylamidine T-2307 maintains in vitro and in vivo activity against echinocandin-resistant Candida albicans. Antimicrob Agents Chemother. 2015;59:1341–1343. doi:10.1128/AAC.04228-14
   PubMed Web of Science ®Google Scholar
• Wiederhold NP, Najvar LK, Jaramillo R, et al. The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against Candida auris. Antimicrob Agents Chemother. 2020;64:e02198–19. doi:10.1128/AAC.02198-19
   PubMed Web of Science ®Google Scholar
• Bassetti M, Marchetti M, Chakrabarti A, et al. A research agenda on the management of intra-abdominal candidiasis: results from a consensus of multinational experts. Intensive Care Med. 2013;39:2092–2106. doi:10.1007/s00134-013-3109-3
   PubMed Web of Science ®Google Scholar
• Bassetti M, Righi E, Ansaldi F, et al. A multicenter multinational study of abdominal candidiasis: epidemiology, outcomes and predictors of mortality. Intensive Care Med. 2015;41:1601–1610. doi:10.1007/s00134-015-3866-2
   PubMed Web of Science ®Google Scholar
• Kullberg BJ, van de Veerdonk F, Netea MG. Immunotherapy: a potential adjunctive treatment for fungal infection. Curr Opin Infect Dis. 2014;27:511–516. doi:10.1097/QCO.0000000000000105
   PubMed Web of Science ®Google Scholar
• Delsing CE, Gresnigt MS, Leentjens J, et al. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infect Dis. 2014;14:166. doi:10.1186/1471-2334-14-166
   PubMed Web of Science ®Google Scholar