Addressing current medical needs in invasive fungal infection prevention and treatment with new antifungal agents, strategies and formulations

Expert Opinion on Emerging Drugs

Volumn 16, Issue 3, 2011, Pages 559-586

  Pitman, Stuart K ^a,b   Drew, Richard H ^c,d   Perfect, John R ^b  

^a Campbell University College of Pharmacy and Health Sciences   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c CAMPBELL UNIVERSITY   (United States)

^d DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

combination therapy; dose escalation; invasive fungal infection; isavuconazole; new antifungals

Indexed keywords

ALBACONAZOLE; AMINOCANDIN; AMPHOTERICIN B; AMPHOTERICIN B DEOXYCHOLATE; AMPHOTERICIN B LIPID COMPLEX; ANIDULAFUNGIN; ANTIFUNGAL AGENT; BAL 8349; BAL 8728; BAY 108888; BMS 379224; CASPOFUNGIN; DEFERASIROX; E 1210; ECHINOCANDIN; EFUNGUMAB; FG 3409; FG 3622; FLUCONAZOLE; FLUCYTOSINE; FR 290581; HMR 3270; ICOFUNGIPEN; IP 960; IRON CHELATING AGENT; ISAVUCONAZOLE; ISAVUCONAZONIUM; ITRACONAZOLE; LORAMYC; MGCD 290; MICAFUNGIN; MICONAZOLE; MK 3118; MONOCLONAL ANTIBODY; NDV 3; NIKKOMYCIN Z; NP 339; ORAVIG; PEV 7; POLYENE ANTIBIOTIC AGENT; POSACONAZOLE; PRAMICONAZOLE; R 135853; RAVUCONAZOLE; RO 0098557; SERTACONAZOLE; SPA S 843; SPK 843; T 2307; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORICONAZOLE; VT 11611129; W 0027;

ANTIFUNGAL RESISTANCE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FORMULATION; DRUG SAFETY; ELECTROLYTE DISTURBANCE; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; HALLUCINATION; HEMATOLOGIC DISEASE; HUMAN; INJECTION SITE REACTION; LIVER DISEASE; LIVER FUNCTION TEST; NEPHROTOXICITY; NONHUMAN; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHOTOTOXICITY; REVIEW; SIDE EFFECT; SKIN CANCER; SYSTEMIC MYCOSIS;

EID: 80052011287     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2011.607811     Document Type: Review

References (290)

1. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39(3):309-17
2. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 2010;50(8):1091-100
3. Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: Analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin Infect Dis 2009;48(3):265-73
4. Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 2010;50(8):1101-11
5. Neofytos D, Fishman JA, Horn D, et al. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients. Transpl Infect Dis 2010;12(3):220-9
6. Gudlaugsson O, Gillespie S, Lee K, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 2003;37(9):1172-7
7. Menzin J, Meyers JL, Friedman M, et al. The economic costs to United States hospitals of invasive fungal infections in transplant patients. Am J Infect Control 2011;39(4):e15-20
8. Menzin J, Meyers JL, Friedman M, et al. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients. Am J Health Syst Pharm 2009;66(19):1711-17
9. Zilberberg MD, Shorr AF, Kollef MH. Secular trends in candidemia-related hospitalization in the United States, 2000-2005. Infect Control Hosp Epidemiol 2008;29(10):978-80
10. HPA. Candidaemia reports, England, Wales, and Northern Ireland: 2003. Commun Dis Rep CDR Wkly 14[43]. 10-21-2004. 5-16-2011
11. Diekema DJ, Messer SA, Boyken LB, et al. In vitro activity of seven systemically active antifungal agents against a large global collection of rare Candida species as determined by CLSI broth microdilution methods. J Clin Microbiol 2009;47(10):3170-7
12. Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002;34(7):909-17
13. Almyroudis NG, Sutton DA, Fothergill AW, et al. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother 2007;51(7):2587-90
14. Pfaller MA, Diekema DJ. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 2010;36(1):1-53 This review offers comprehensive details regarding the epidemiology and susceptibility of North American opportunistic and endemic fungal pathogens.
15. Imhof A, Balajee SA, Fredricks DN, et al. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis 2004;39(5):743-6
16. Ambrosioni J, Bouchuiguir-Wafa K, Garbino J. Emerging invasive zygomycosis in a tertiary care center: Epidemiology and associated risk factors. Int J Infect Dis 2010;14(Suppl 3):e100-3
17. Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: Ten years' experience at a cancer center and implications for management. Blood 1997;90(3):999-1008
18. Girmenia C, Pagano L, Corvatta L, et al. The epidemiology of fusariosis in patients with haematological diseases. Gimema Infection Programme. Br J Haematol 2000;111(1):272-6
19. Perkhofer S, Lass-Florl C, Hell M, et al. The nationwide austrian aspergillus registry: A prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients. Int J Antimicrob Agents 2010;36(6):531-6
20. Skiada A, Pagano L, Groll A, et al. Zygomycosis in Europe: Analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) working group on zygomycosis between 2005 and 2007. Clin Microbiol Infect 2011; [Epub ahead of print]
21. Pagano L, Caira M, Candoni A, et al. The epidemiology of fungal infections in patients with hematologic malignancies: The SEIFEM-2004 study. Haematologica 2006;91(8):1068-75
22. Drew RH. Polyenes for prevention and treatment of invasive fungal infections. In: Ghannoum MA, Perfect JR. editors. Antifungal therapy. Informa Healthcare USA, Inc; New York; 2010. p. 163-83
23. Dodds Ashley E. Pharmacology of azole antifungal agents. In: Ghannoum MA, Perfect JR. editors. Antifungal therapy. Informa Healthcare, Inc; New York; 2010. p. 199-218
24. Purkins L, Wood N, Ghahramani P, et al. Pharmacokinetics and safety of voriconazole following intravenous- To oral-dose escalation regimens. Antimicrob Agents Chemother 2002;46(8):2546-53
25. Howard A, Hoffman J, Sheth A. Clinical application of voriconazole concentrations in the treatment of invasive aspergillosis. Ann Pharmacother 2008;42(12):1859-64
26. Gubbins PO, Krishna G, Sansone-Parsons A, et al. Pharmacokinetics and safety of oral posaconazole in neutropenic stem cell transplant recipients. Antimicrob Agents Chemother 2006;50(6):1993-9
27. Ullmann AJ, Cornely OA, Burchardt A, et al. Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother 2006;50(2):658-66
28. Courtney R, Wexler D, Radwanski E, et al. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol 2004;57(2):218-22
29. Alffenaar JW, Van Assen S, Van Der Werf TS, et al. Omeprazole significantly reduces posaconazole serum trough level. Clin Infect Dis 2009;48(6):839
30. Johnson LB, Kauffman CA. Voriconazole: A new triazole antifungal agent. Clin Infect Dis 2003;36(5):630-7
31. Abel S, Allan R, Gandelman K, et al. Pharmacokinetics, safety and tolerance of voriconazole in renally impaired subjects: Two prospective, multicentre, open-label, parallel-group volunteer studies. Clin Drug Investig 2008;28(7):409-20
32. Lipp HP. Antifungal agents-clinical pharmacokinetics and drug interactions. Mycoses 2008;51(Suppl 1):7-18
33. Yakiwchuk EM, Foisy MM, Hughes CA. Complexity of interactions between voriconazole and antiretroviral agents. Ann Pharmacother 2008;42(5):698-703
34. Vohringer S, Schrum J, Ott H, Hoger PH. Severe phototoxicity associated with long-term voriconazole treatment. J Dtsch Dermatol Ges 2011;9(4):274-6
35. Kadikoy H, Barkmeier A, Peck B, Carvounis PE. Persistent photopsia following course of oral voriconazole. J Ocul Pharmacol Ther 2010;26(4):387-8
36. Wang JL, Chang CH, Young-Xu Y, Chan KA. Systematic review and meta-analysis of the tolerability and hepatotoxicity of antifungals in empirical and definitive therapy for invasive fungal infection. Antimicrob Agents Chemother 2010;54(6):2409-19
37. Zonios DI, Gea-Banacloche J, Childs R, Bennett JE. Hallucinations during voriconazole therapy. Clin Infect Dis 2008;47(1):e7-10
38. Vadnerkar A, Nguyen MH, Mitsani D, et al. Voriconazole exposure and geographic location are independent risk factors for squamous cell carcinoma of the skin among lung transplant recipients. J Heart Lung Transplant 2010;29(11):1240-4
39. Thompson GRI, Cadena J, Patterson TF. Overview of antifungal agents. Clin Chest Med 2009;30(2):203-15; v
40. Johnson MD, Mohr J. Echinocandins for prevention and treatment of invasive fungal infections. In: Ghannoum MA, Perfect JR. editors. Antifungal therapy. Informa Healthcare, Inc; New York; 2010. p. 219-42
41. Pfaller MA, Castanheira M, Messer SA, et al. Echinocandin and triazole antifungal susceptibility profiles for Candida spp., Cryptococcus neoformans, and Aspergillus fumigatus: Application of new CLSI clinical breakpoints and epidemiologic cutoff values to characterize resistance in the SENTRY Antimicrobial Surveillance Program (2009). Diagn Microbiol Infect Dis 2011;69(1):45-50
42. Pfaller M, Boyken L, Hollis R, et al. Use of epidemiological cutoff values to examine 9-year trends in susceptibility of Candida species to anidulafungin, caspofungin, and micafungin. J Clin Microbiol 2011;49(2):624-9
43. Drew RH. Flucyosine. In: Ghannoum MA, Perfect JR. editors. Antifungal therapy. Informa Healthcare, Inc; New York; 2010. p. 184-98
44. Kanafani ZA, Perfect JR. Antimicrobial resistance: Resistance to antifungal agents: Mechanisms and clinical impact. Clin Infect Dis 2008;46(1):120-8
45. 2009 Top 200 generic drugs by retail dollar. Drug Topics, 1-3. 6-17-2010. 5-16-2011
46. 2009 Top 200 generic drugs by total prescriptions. Drug Topics, 1-3. 6-17-2010. 5-16-2011
47. Pakyz AL, Gurgle HE, Oinonen MJ. Antifungal use in hospitalized adults in U.S. academic health centers. Am J Health Syst Pharm 2011;68(5):415-18
48. Johnson MD, Perfect JR. Use of antifungal combination therapy: Agents, order, and timing. Curr Fungal Infect Rep 2010;4(2):87-95 This review describes in vitro, in vivo and clinical data regarding the use of antifungal combination therapy and reviews current IDSA combination therapy recommendations.
49. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis 2010;50(3):291-322
50. Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008;47(3):364-71
51. Walsh TJ, Kontoyiannis DP. Editorial commentary: What is the role of combination therapy in management of zygomycosis? Clin Infect Dis 2008;47(3):372-4
52. Migoya EM, Mistry GC, Stone JA, et al. Safety and pharmacokinetics of higher doses of caspofungin in healthy adult participants. J Clin Pharmacol 2011;51(2):202-11
53. Betts RF, Nucci M, Talwar D, et al. A multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 2009;48(12):1676-84
54. NCT00404092. Caspofungin maximum tolerated dose in patients with invasive aspergillosis. 6-28-2011. 5-11-2011
55. Hiemenz J, Cagnoni P, Simpson D, et al. Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant. Antimicrob Agents Chemother 2005;49(4):1331-6
56. Sirohi B, Powles RL, Chopra R, et al. A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation. Bone Marrow Transplant 2006;38(1):47-51
57. Ota Y, Tatsuno K, Okugawa S, et al. Relationship between the initial dose of micafungin and its efficacy in patients with candidemia. J Infect Chemother 2007;13(4):208-12
58. Pound MW, Townsend ML, Drew RH. Echinocandin pharmacodynamics: Review and clinical implications. J Antimicrob Chemother 2010;65(6):1108-18 This review discusses echinocandin dose escalation and the 'eagle effect'.
59. Dupont B. Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother 2002;49(Suppl 1):31-6
60. Ellis M, Bernsen R, Ali-Zadeh H, et al. A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever. J Med Microbiol 2009;58(Pt 11):1474-85
61. Raad II, Hanna HA, Boktour M, et al. Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: Posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin. Leukemia 2008;22(3):496-503
62. Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: A randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis 2007;44(10):1289-97 This double-blind randomized trial compared standard dose (3 mg/kg/day) with high-dose liposomal amphotericin B (10 mg/kg/day).
63. McLintock LA, Cook G, Holyoake TL, et al. High loading dose AmBisome is efficacious and well tolerated in the management of invasive fungal infection in hematology patients. Haematologica 2007;92(4):572-3
64. El-Cheikh J, Faucher C, Furst S, et al. High-dose weekly liposomal amphotericin B antifungal prophylaxis following reduced-intensity conditioning allogeneic stem cell transplantation. Bone Marrow Transplant 2007;39(5):301-6
65. Cordonnier C, Mohty M, Faucher C, et al. Safety of a weekly high dose of liposomal amphotericin B for prophylaxis of invasive fungal infection in immunocompromised patients: PROPHYSOME Study. Int J Antimicrob Agents 2008;31(2):135-41
66. Bicanic T, Wood R, Meintjes G, et al. High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: A randomized trial. Clin Infect Dis 2008;47(1):123-30
67. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011;52(4):e56-93
68. Maertens J, Theunissen K, Verhoef G, et al. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: A prospective feasibility study. Clin Infect Dis 2005;41(9):1242-50
69. Cordonnier C, Pautas C, Maury S, et al. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: A randomized, controlled trial. Clin Infect Dis 2009;48(8):1042-51 This randomized, open label, non-inferiority trial compared the strategies of preemptive versus empiric antifungal therapy in high-risk febrile neutropenic patients.
70. Marr KA, Leisenring W, Bow E. Empirical versus preemptive antifungal therapy for fever during neutropenia. Clin Infect Dis 2009;49(7):1138-9
71. Hebart H, Klingspor L, Klingebiel T, et al. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant 2009;43(7):553-61
72. Bensadoun RJ, Daoud J, El GB, et al. Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis: A prospective, randomized, single-blind, multicenter, comparative, phase III trial in patients treated with radiotherapy for head and neck cancer. Cancer 2008;112(1):204-11
73. Vazquez JA, Patton LL, Epstein JB, et al. Randomized, comparative, double-blind, double-dummy, multicenter trial of miconazole buccal tablet and clotrimazole troches for the treatment of oropharyngeal candidiasis: Study of miconazole Lauriad(R) efficacy and safety (SMiLES). HIV Clin Trials 2010;11(4):186-96
74. Gligorov J, Bastit L, Gervais H, et al. Prevalence and treatment management of oropharyngeal candidiasis in cancer patients: Results of the French candidoscope study. Int J Radiat Oncol Biol Phys 2011;80(2):532-9
75. NCT01075984. Pharmacokinetics, safety, and tolerability of intravenous posaconazole solution followed by oral posaconazole suspension in subjects at high risk for invasive fungal infections (study P05520AM1). 4-20-2011. 6-1-2011
76. Torrado JJ, Espada R, Ballesteros MP, Torrado-Santiago S. Amphotericin B formulations and drug targeting. J Pharm Sci 2008;97(7):2405-25
77. Shadkhan Y, Segal E, Bor A, et al. The use of commercially available lipid emulsions for the preparation of amphotericin B-lipid admixtures. J Antimicrob Chemother 1997;39(5):655-8
78. Offner F, Krcmery V, Boogaerts M, et al. Liposomal nystatin in patients with invasive aspergillosis refractory to or intolerant of amphotericin B. Antimicrob Agents Chemother 2004;48(12):4808-12
79. Khan MA, Faisal SM, Mohammad O. Safety, efficacy and pharmacokinetics of tuftsin-loaded nystatin liposomes in murine model. J Drug Target 2006;14(4):233-41
80. Chen W, Gu B, Wang H, et al. Development and evaluation of novel itraconazole-loaded intravenous nanoparticles. Int J Pharm 2008;362(1-2):133-40
81. Chen W, Zhan C, Gu B, et al. Targeted brain delivery of itraconazole via RVG29 anchored nanoparticles. J Drug Target 2011;19(3):228-34
82. Alvarez CA, Wiederhold NP, McConville JT, et al. Aerosolized nanostructured itraconazole as prophylaxis against invasive pulmonary aspergillosis. J Infect 2007;55(1):68-74
83. Hoeben BJ, Burgess DS, McConville JT, et al. In vivo efficacy of aerosolized nanostructured itraconazole formulations for prevention of invasive pulmonary aspergillosis. Antimicrob Agents Chemother 2006;50(4):1552-4
84. Pasqualotto AC, Denning DW. New and emerging treatments for fungal infections. J Antimicrob Chemother 2008;61(Suppl 1):i19-30
85. Warn PA, Sharp A, Denning DW. In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp. J Antimicrob Chemother 2006;57(1):135-8
86. Guinea J, Pelaez T, Recio S, et al. In vitro antifungal activities of isavuconazole (BAL4815), voriconazole, and fluconazole against 1,007 isolates of zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium species. Antimicrob Agents Chemother 2008;52(4):1396-400
87. Perkhofer S, Lechner V, Lass-Florl C. In vitro activity of isavuconazole against aspergillus species and zygomycetes according to the methodology of the European committee on antimicrobial susceptibility testing. Antimicrob Agents Chemother 2009;53(4):1645-7
88. Seifert H, Aurbach U, Stefanik D, Cornely O. In vitro activities of isavuconazole and other antifungal agents against candida bloodstream isolates. Antimicrob Agents Chemother 2007;51(5):1818-21
89. Illnait-Zaragozi MT, Martinez GF, Curfs-Breuker I, et al. In vitro activity of the new azole isavuconazole (BAL4815) compared with six other antifungal agents against 162 cryptococcus neoformans isolates from Cuba. Antimicrob Agents Chemother 2008;52(4):1580-2
90. Guinea J, Hagen F, Pelaez T, et al. Antifungal susceptibility, serotyping, and genotyping of clinical cryptococcus neoformans isolates collected during 18 years in a single institution in Madrid, Spain. Med Mycol 2010;48(7):942-8
91. Hagen F, Illnait-Zaragozi MT, Bartlett KH, et al. In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental cryptococcus gattii isolates. Antimicrob Agents Chemother 2010;54(12):5139-45
92. Gonzalez GM. In vitro activities of isavuconazole against opportunistic filamentous and dimorphic fungi. Med Mycol 2009;47(1):71-6
93. Yamazaki T, Inagaki Y, Fujii T, et al. In vitro activity of isavuconazole against 140 reference fungal strains and 165 clinically isolated yeasts from Japan. Int J Antimicrob Agents 2010;36(4):324-31
94. Guinea J, Recio S, Escribano P, et al. In vitro antifungal activities of isavuconazole and comparators against rare yeast pathogens. Antimicrob Agents Chemother 2010;54(9):4012-15
95. Thompson GR III, Wiederhold NP, Sutton DA, et al. In vitro activity of isavuconazole against Trichosporon, Rhodotorula, Geotrichum, Saccharomyces and Pichia species. J Antimicrob Chemother 2009;64(1):79-83
96. Majithiya J, Sharp A, Parmar A, et al. Efficacy of isavuconazole, voriconazole and fluconazole in temporarily neutropenic murine models of disseminated Candida tropicalis and Candida krusei. J Antimicrob Chemother 2009;63(1):161-6
97. Schmitt-Hoffmann A, Roos B, Heep M, et al. Single-ascending-dose pharmacokinetics and safety of the novel broad-spectrum antifungal triazole BAL4815 after intravenous infusions (50, 100, and 200 milligrams) and oral administrations (100, 200, and 400 milligrams) of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother 2006;50(1):279-85
98. Girmenia C. New generation azole antifungals in clinical investigation. Expert Opin Investig Drugs 2009;18(9):1279-95
99. Schmitt-Hoffmann A, Roos B, Maares J, et al. Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers. Antimicrob Agents Chemother 2006;50(1):286-93
100. Schmitt-Hoffmann A, Roos B, Spickermann J, et al. Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557. Antimicrob Agents Chemother 2009;53(11):4885-90
101. Warn PA, Sharp A, Parmar A, et al. Pharmacokinetics and pharmacodynamics of a novel triazole, isavuconazole: Mathematical modeling, importance of tissue concentrations, and impact of immune status on antifungal effect. Antimicrob Agents Chemother 2009;53(8):3453-61
102. Viljoen JJ, Mitha I, Heep M, Ghannoum M. Efficacy, safety, and tolerability of three different dosing regimens of BAL8557 vs. fluconazole in a double-blind, randomized, multicenter trial for the treatment of esophageal candidiasis in immunocompromised adults [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2005 Annual Meeting. 2005. 5-31-2011
103. NCT00413439. Safety, efficacy and pharmacokinetics of an antifungal in patients undergoing chemotherapy. 9-13-2007. 5-12-2011
104. NCT00413218. Isavuconazole (BAL8557) in the treatment of candidemia and other invasive Candida infections. 3-31-2011. 5-12-2011
105. NCT00412893. Isavuconazole (BAL8557) for primary treatment of invasive aspergillosis. 3-31-2011. 5-12-2011
106. NCT00634049. Isavuconazole in the treatment of renally impaired aspergillosis and rare fungi. 3-31-2011. 5-12-2011
107. Gonzalez GM, Elizondo M, Ayala J. Trends in species distribution and susceptibility of bloodstream isolates of candida collected in Monterrey, Mexico, to seven antifungal agents: Results of a 3-year (2004 to 2007) surveillance study. J Clin Microbiol 2008;46(9):2902-5
108. Messer SA, Jones RN, Fritsche TR. International surveillance of Candida spp. and Aspergillus spp.: Report from the SENTRY antimicrobial surveillance program (2003). J Clin Microbiol 2006;44(5):1782-7
109. St-Germain G, Laverdiere M, Pelletier R, et al. Epidemiology and antifungal susceptibility of bloodstream candida isolates in quebec: Report on 453 cases between 2003 and 2005. Can J Infect Dis Med Microbiol 2008;19(1):55-62
110. Pfaller MA, Messer SA, Hollis RJ, et al. In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp. Antimicrob Agents Chemother 2002;46(6):1723-7
111. Cuenca-Estrella M, Gomez-Lopez A, Mellado E, et al. In vitro activities of ravuconazole and four other antifungal agents against fluconazole-resistant or - susceptible clinical yeast isolates. Antimicrob Agents Chemother 2004;48(8):3107-11
112. Pfaller MA, Diekema DJ, Messer SA, et al. In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole and three comparative antifungal agents. Diagn Microbiol Infect Dis 2004;48(2):101-5
113. Baddley JW, Marr KA, Andes DR, et al. Patterns of susceptibility of Aspergillus isolates recovered from patients enrolled in the Transplant-Associated Infection Surveillance Network. J Clin Microbiol 2009;47(10):3271-5
114. Diekema DJ, Messer SA, Hollis RJ, et al. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol 2003;41(8):3623-6
115. Cuenca-Estrella M, Gomez-Lopez A, Mellado E, et al. In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi. Antimicrob Agents Chemother 2005;49(12):5136-8
116. Alastruey-Izquierdo A, Cuenca-Estrella M, Monzon A, et al. Antifungal susceptibility profile of clinical Fusarium spp. isolates identified by molecular methods. J Antimicrob Chemother 2008;61(4):805-9
117. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother 2001;45(7):2151-3
118. Minassian B, Huczko E, Washo T, et al. In vitro activity of ravuconazole against zygomycetes, Scedosporium and Fusarium isolates. Clin Microbiol Infect 2003;9(12):1250-2
119. Pfaller MA, Messer SA, Boyken L, et al. Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990 to 2004). J Clin Microbiol 2005;43(5):2163-7
120. Perkins A, Gomez-Lopez A, Mellado E, et al. Rates of antifungal resistance among Spanish clinical isolates of Cryptococcus neoformans var. neoformans. J Antimicrob Chemother 2005;56(6):1144-7
121. Trilles L, Fernandez-Torres B, Lazera MS, et al. In vitro antifungal susceptibility of Cryptococcus gattii. J Clin Microbiol 2004;42(10):4815-17
122. Diekema DJ, Petroelje B, Messer SA, et al. Activities of available and investigational antifungal agents against rhodotorula species. J Clin Microbiol 2005;43(1):476-8
123. Wheat LJ, Connolly P, Smedema M, et al. Activity of newer triazoles against histoplasma capsulatum from patients with AIDS who failed fluconazole. J Antimicrob Chemother 2006;57(6):1235-9
124. Petraitiene R, Petraitis V, Lyman CA, et al. Efficacy, safety, and plasma pharmacokinetics of escalating dosages of intravenously administered ravuconazole lysine phosphoester for treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother 2004;48(4):1188-96
125. Roberts J, Schock K, Marino S, Andriole VT. Efficacies of two new antifungal agents, the triazole ravuconazole and the echinocandin LY-303366, in an experimental model of invasive aspergillosis. Antimicrob Agents Chemother 2000;44(12):3381-8
126. Petraitis V, Petraitiene R, Sarafandi AA, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: Synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis 2003;187(12):1834-43
127. Meletiadis J, Petraitis V, Petraitiene R, et al. Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: In vitro and in vivo correlation. J Infect Dis 2006;194(7):1008-18
128. Hata K, Kimura J, Miki H, et al. Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis. Antimicrob Agents Chemother 1996;40(10):2243-7
129. Hata K, Kimura J, Miki H, et al. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum. Antimicrob Agents Chemother 1996;40(10):2237-42
130. Clemons KV, Stevens DA. Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice. Antimicrob Agents Chemother 2001;45(12):3433-6
131. Clemons KV, Martinez M, Calderon L, Stevens DA. Efficacy of ravuconazole in treatment of systemic murine histoplasmosis. Antimicrob Agents Chemother 2002;46(3):922-4
132. Mikamo H, Yin XH, Hayasaki Y, et al. Effect of ravuconazole, a new triazole antifungal, in a rat intraabdominal abscess model. Chemotherapy 2001;47(5):377-80
133. Urbina JA, Payares G, Sanoja C, et al. In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease. Int J Antimicrob Agents 2003;21(1):27-38
134. Diniz Lde F, Caldas IS, Guedes PM, et al. Effects of ravuconazole treatment on parasite load and immune response in dogs experimentally infected with trypanosoma cruzi. Antimicrob Agents Chemother 2010;54(7):2979-86
135. Pasqualotto AC, Thiele KO, Goldani LZ. Novel triazole antifungal drugs: Focus on isavuconazole, ravuconazole and albaconazole. Curr Opin Investig Drugs 2010;11(2):165-74
136. Marino M, Mummaneni V, Norton J, et al. Ravuconazole exposure-response relationship in HIV+ patients with oropharyngeal candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2001 Annual Meeting. 2001. 5-31-2011
137. Groll AH, Mickiene D, Petraitis V, et al. Compartmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its di-lysine phosphoester prodrug (BMS-379224) in rabbits. J Antimicrob Chemother 2005;56(5):899-907
138. Andes D, Marchillo K, Stamstad T, Conklin R. In vivo pharmacodynamics of a new triazole, ravuconazole, in a murine candidiasis model. Antimicrob Agents Chemother 2003;47(4):1193-9
139. Gupta AK, Leonardi C, Stoltz RR, et al. A phase I/II randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy, safety and pharmacokinetics of ravuconazole in the treatment of onychomycosis. J Eur Acad Dermatol Venereol 2005;19(4):437-43
140. NCT00064311. Ravuconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation. 2010. 5-14-2011
141. Beale E, Queiroz-Telles F, Banhegyi D, et al. Randomized, double-blind study of the safety and antifungal activity of ravuconazole relative to fluconazole in esophageal candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2001 Annual Meeting; 5-31-2011
142. Morera-Lopez Y, Torres-Rodriguez JM, Jimenez-Cabello T, Baro-Tomas T. Cryptococcus gattii: In vitro susceptibility to the new antifungal albaconazole versus fluconazole and voriconazole. Med Mycol 2005;43(6):505-10
143. Ramos G, Cuenca-Estrella M, Monzon A, Rodriguez-Tudela JL. In vitro comparative activity of UR-9825, itraconazole and fluconazole against clinical isolates of Candida spp. J Antimicrob Chemother 1999;44(2):283-6
144. Alves SH, Da Matta DA, Azevedo AC, et al. In vitro activities of new and conventional antimycotics against fluconazole-susceptible and non-susceptible Brazilian Candida spp. isolates. Mycoses 2006;49(3):220-5
145. Urbina JA, Lira R, Visbal G, Bartroli J. In vitro antiproliferative effects and mechanism of action of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma (Schizotrypanum) cruzi. Antimicrob Agents Chemother 2000;44(9):2498-502
146. Capilla J, Ortoneda M, Pastor FJ, Guarro J. In vitro antifungal activities of the new triazole UR-9825 against clinically important filamentous fungi. Antimicrob Agents Chemother 2001;45(9):2635-7
147. Gonzalez GM, Robledo E, Garza-Gonzalez E, et al. Efficacy of albaconazole against Candida albicans in a vaginitis model. Antimicrob Agents Chemother 2009;53(10):4540-1
148. Guedes PM, Urbina JA, de Lana M, et al. Activity of the new triazole derivative albaconazole against trypanosoma (Schizotrypanum) cruzi in dog hosts. Antimicrob Agents Chemother 2004;48(11):4286-92
149. Miller JL, Schell WA, Wills EA, et al. In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans. Antimicrob Agents Chemother 2004;48(2):384-7
150. Capilla J, Yustes C, Mayayo E, et al. Efficacy of albaconazole (UR-9825) in treatment of disseminated scedosporium prolificans infection in rabbits. Antimicrob Agents Chemother 2003;47(6):1948-51
151. Bartroli J, Turmo E, Alguero M, et al. New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4 (3H)-quinazolinones. J Med Chem 1998;41(11):1869-82
152. Ramis J, Izquierdo I, Lurigados C, et al. First administration into man of UR- 9825: A new triazole class of antifungal agent [abstract]. 6th Congress of the European Confederation of Medical Mycology Societies (ECMM 6th). 2000. 5-30-2011
153. NCT01039883. A study to compare the blood levels of albaconazole in healthy subjects who have received a single dose of 400 mg albaconazole as a tablet versus albaconazole as a capsule. 2-8-2010. 5-12-2011
154. NCT01014962. A study of the effects of increasing doses of a drug for the treatment of nail fungus. 2-21-2010. 5-12-2011
155. NCT00509275. A study to evaluate efficacy and safety of three W0027 regimens with placebo in the treatment of moccasin type tinea pedis (MTTP). 9-10-2008. 5-14-2011
156. Bartroli X, Uriach J. A clinical multicenter study comparing efficacy and tolerability between five single oral doses of albaconazole and fluconazole 150 mg single dose in acute vulvovaginal candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2005 Annual Meeting; 5-30-2011
157. NCT00730405. Efficacy and safety study of 4 dose regimens of oral albaconazole in subjects with distal subungual onychomycosis. 8-6-2010. 5-14-2011
158. Odds F, Ausma J, Van Gerven F, et al. In vitro and in vivo activities of the novel azole antifungal agent r126638. Antimicrob Agents Chemother 2004;48(2):388-91
159. Vanden Bossche H, Ausma J, Bohets H, et al. The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother 2004;48(9):3272-8
160. De Wit K, Paulussen C, Matheeussen A, et al. In vitro profiling of pramiconazole and in vivo evaluation in microsporum canis dermatitis and candida albicans vaginitis laboratory models. Antimicrob Agents Chemother 2010;54(11):4927-9
161. Meerpoel L, Backx LJ, Van der Veken LJ, et al. Synthesis and in vitro and in vivo structure-activity relationships of novel antifungal triazoles for dermatology. J Med Chem 2005;48(6):2184-93
162. Faergemann J, Ausma J, Borgers M. In vitro activity of R126638 and ketoconazole against malassezia species. Acta Derm Venereol 2006;86(4):312-15
163. Ausma J, Pennick G, Bohets H, et al. Absence of an active metabolite for the triazole antifungal pramiconazole. Acta Derm Venereol 2007;87(1):22-6
164. Faergemann J, Ausma J, Vandeplassche L, Borgers M. The efficacy of oral treatment with pramiconazole in pityriasis versicolor: A phase II a trial. Br J Dermatol 2007;156(6):1385-8
165. Faergemann J, Todd G, Pather S, et al. A double-blind, randomized, placebo-controlled, dose-finding study of oral pramiconazole in the treatment of pityriasis versicolor. J Am Acad Dermatol 2009;61(6):971-6
166. Decroix J, Ausma J, Cauwenbergh G, et al. The efficacy of oral treatment with pramiconazole in tinea pedis and tinea cruris/corporis: Two exploratory phase IIa trials. Br J Dermatol 2008;158(4):854-6
167. Pierard GE, Ausma J, Henry F, et al. A pilot study on seborrheic dermatitis using pramiconazole as a potent oral anti-malassezia agent. Dermatology 2007;214(2):162-9
168. Donders G, Ausma J, Wouters L, et al. Efficacy of a single oral dose of 200 mg pramiconazole in vulvovaginal yeast infections: An exploratory phase IIa trial. Acta Derm Venereol 2008;88(5):462-6
169. Ibrahim AS, Gebremariam T, Luo G, et al. Combination therapy of murine mucormycosis or aspergillosis with iron chelation, polyenes and echinocandins. Antimicrob Agents Chemother 2011;55(4):1768-70
170. Ibrahim AS, Gebremariam T, French SW, et al. The iron chelator deferasirox enhances liposomal amphotericin B efficacy in treating murine invasive pulmonary aspergillosis. J Antimicrob Chemother 2010;65(2):289-92
171. Reed C, Ibrahim A. Edwards JE Jr, Walot I, Spellberg B. Deferasirox, an iron-chelating agent, as salvage therapy for rhinocerebral mucormycosis. Antimicrob Agents Chemother 2006;50(11):3968-9
172. Busca A, Marmont F, Locatelli F, et al. Combined antifungal therapy, iron chelation and surgical resection as treatment of hepatic zygomycosis in a patient with haematological malignancy. Mycoses 2010;53(3):275-8
173. Symeonidis AS. The role of iron and iron chelators in zygomycosis. Clin Microbiol Infect 2009;15(Suppl 5):26-32
174. Soummer A, Mathonnet A, Scatton O, et al. Failure of deferasirox, an iron chelator agent, combined with antifungals in a case of severe zygomycosis. Antimicrob Agents Chemother 2008;52(4):1585-6
175. NCT00419770. The deferasirox-AmBisome therapy for mucormycosis (DEFEAT Mucor) study. 3-29-2011. 5-13-2011
176. Zarember KA, Cruz AR, Huang CY, Gallin JI. Antifungal activities of natural and synthetic iron chelators alone and in combination with azole and polyene antibiotics against Aspergillus fumigatus. Antimicrob Agents Chemother 2009;53(6):2654-6
177. Ibrahim AS, Edwards JE Jr, Fu Y, Spellberg B. Deferiprone iron chelation as a novel therapy for experimental mucormycosis. J Antimicrob Chemother 2006;58(5):1070-3
178. Ostrosky-Zeichner L, Casadevall A, Galgiani JN, et al. An insight into the antifungal pipeline: Selected new molecules and beyond. Nat Rev Drug Discov 2010;9(9):719-27
179. Hector RF, Zimmer BL, Pappagianis D. Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis. Antimicrob Agents Chemother 1990;34(4):587-93
180. Sandovsky-Losica H, Shwartzman R, Lahat Y, Segal E. Antifungal activity against Candida albicans of nikkomycin Z in combination with caspofungin, voriconazole or amphotericin B. J Antimicrob Chemother 2008;62(3):635-7
181. Tariq VN, Scott EM, McCain NE. Use of decimal assay for additivity to demonstrate synergy in pair combinations of econazole, nikkomycin Z, and ibuprofen against Candida albicans in vitro. Antimicrob Agents Chemother 1995;39(12):2615-19
182. Li RK, Rinaldi MG. In vitro antifungal activity of nikkomycin Z in combination with fluconazole or itraconazole. Antimicrob Agents Chemother 1999;43(6):1401-5
183. Ganesan LT, Manavathu EK, Cutright JL, et al. In vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. Clin Microbiol Infect 2004;10(11):961-6
184. Stevens DA. Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin synthase inhibitor (Nikkomycin Z) for inhibition and killing of fungal pathogens. Antimicrob Agents Chemother 2000;44(9):2547-8
185. Steinbach WJ, Cramer RA Jr, Perfect BZ, et al. Calcineurin inhibition or mutation enhances cell wall inhibitors against aspergillus fumigatus. Antimicrob Agents Chemother 2007;51(8):2979-81
186. Hector RF, Davidson AP, Johnson SM. Comparison of susceptibility of fungal isolates to lufenuron and nikkomycin Z alone or in combination with itraconazole. Am J Vet Res 2005;66(6):1090-3
187. Luque JC, Clemons KV, Stevens DA. Efficacy of micafungin alone or in combination against systemic murine aspergillosis. Antimicrob Agents Chemother 2003;47(4):1452-5
188. Clemons KV, Stevens DA. Efficacy of micafungin alone or in combination against experimental pulmonary aspergillosis. Med Mycol 2006;44(1):69-73
189. Goldberg J, Connolly P, Schnizlein-Bick C, et al. Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment of histoplasmosis in a murine model. Antimicrob Agents Chemother 2000;44(6):1624-9
190. Graybill JR, Najvar LK, Bocanegra R, et al. Efficacy of nikkomycin Z in the treatment of murine histoplasmosis. Antimicrob Agents Chemother 1998;42(9):2371-4
191. Clemons KV, Stevens DA. Efficacy of nikkomycin Z against experimental pulmonary blastomycosis. Antimicrob Agents Chemother 1997;41(9):2026-8
192. Nix DE, Swezey RR, Hector R, Galgiani JN. Pharmacokinetics of nikkomycin Z after single rising oral doses. Antimicrob Agents Chemother 2009;53(6):2517-21
193. Strippoli V, D'Auria FD, Simonetti G, et al. Anticandidal activity of SPA-S-843, a new polyenic drug. J Antimicrob Chemother 2000;45(2):235-7
194. Rimaroli C, Bruzzese T. In vitro activity of a new polyene, SPA-S-843, against yeasts. Antimicrob Agents Chemother 1998;42(11):3012-13
195. Rimaroli C, Bruzzese T. Overview of SPA-S-843 in vitro activity against filamentous fungi. Chemotherapy 2000;46(1):28-35
196. Kakeya H, Miyazaki Y, Senda H, et al. Efficacy of SPK-843, a novel polyene antifungal, in a murine model of systemic cryptococcosis. Antimicrob Agents Chemother 2008;52(5):1871-2
197. Kakeya H, Miyazaki Y, Senda H, et al. Efficacy of SPK-843, a novel polyene antifungal, in comparison with amphotericin B, liposomal amphotericin B, and micafungin against murine pulmonary aspergillosis. Antimicrob Agents Chemother 2008;52(5):1868-70
198. NCT01125644. Efficacy, safety and pharmacokinetics of SPK-843 in the treatment of pulmonary mycosis. 5-1-2010. 5-13-2011
199. Larsen RA, Pappas PG, Perfect J, et al. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob Agents Chemother 2005;49(3):952-8
200. Casadevall A, Cleare W, Feldmesser M, et al. Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. Antimicrob Agents Chemother 1998;42(6):1437-46
201. Hodgetts S, Nooney L, Al-Akeel R, et al. Efungumab and caspofungin: Pre-clinical data supporting synergy. J Antimicrob Chemother 2008;61(5):1132-9
202. Matthews RC, Rigg G, Hodgetts S, et al. Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90. Antimicrob Agents Chemother 2003;47(7):2208-16
203. Nooney L, Matthews RC, Burnie JP. Evaluation of Mycograb, amphotericin B, caspofungin, and fluconazole in combination against cryptococcus neoformans by checkerboard and time-kill methodologies. Diagn Microbiol Infect Dis 2005;51(1):19-29
204. Krenova Z, Pavelka Z, Lokaj P, et al. Successful treatment of life-threatening Candida peritonitis in a child with abdominal non-Hodgkin lymphoma using efungumab and amphotericin B colloid dispersion. J Pediatr Hematol Oncol 2010;32(2):128-30
205. Sutherland A, Ellis D. Treatment of a critically ill child with disseminated Candida glabrata with a recombinant human antibody specific for fungal heat shock protein 90 and liposomal amphotericin B, caspofungin, and voriconazole. Pediatr Crit Care Med 2008;9(4):e23-5
206. Rowlands HE, Morris K, Graham C. Human recombinant antibody against Candida. Pediatr Infect Dis J 2006;25(10):959-60
207. Pachl J, Svoboda P, Jacobs F, et al. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin Infect Dis 2006;42(10):1404-13 This double-blind randomized trial compared liposomal amphotericin B or amphotericin B deoxycholate alone versus each formulation in combination with efungumab.
208. Herbrecht R, Fohrer C, Nivoix Y. Mycograb for the treatment of invasive candidiasis. Clin Infect Dis 2006;43(8):1083-4
209. European Medicines Agency. Questions and answers on recommendations for the refusal of the marketing authorisation for Mycograb. 3-20-2007. 5-30-2011
210. Wirk B. Heat shock protein inhibitors for the treatment of fungal infections. Recent Pathol Antiinfect Drug Discov 2011;6(1):38-44
211. Cassone A. Fungal vaccines: Real progress from real challenges. Lancet Infect Dis 2008;8(2):114-24
212. Levy DA, Bohbot JM, Catalan F, et al. Phase II study of D.651, an oral vaccine designed to prevent recurrences of vulvovaginal candidiasis. Vaccine 1989;7(4):337-40
213. Pappagianis D. Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. The Valley Fever Vaccine Study Group [abstract]. Am Rev Respir Dis 1993;148(3):656-60
214. NCT01067131. Safety and immunogenicity study of a virosomal vaccine against recurrent vulvovaginal Candida infection. 3-2-2010. 5-12-2011
215. NCT01273922. Safety and immunogenicity study of a recombinant protein vaccine (NDV-3) against S. Aureus and Candida. 4-1-2011. 5-13-2011
216. Pfaller MA, Messer SA, Georgopapadakou N, et al. Activity of MGCD290, a hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens. J Clin Microbiol 2009;47(12):3797-804
217. Besterman J, Reid G, Drouin M. F1-862 - Multiple ascending dose phase I studies in healthy subjects demonstrate safety and pharmacokinetics of MGCD290, an oral fungal hos2 inhibitor ± fluconazole [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting. 2010. 5-13-2011
218. Martell LA, Reid G, Martell R, et al. M-1029 - Multiple phase I studies in healthy subjects demonstrate safety and pharmacokinetics of MGCD290, an oral fungal hos2 inhibitor ± fluconazole [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 5-13-2011
219. Marti N, Tarrago C, Palop D, et al. M-350 - Biological characterization of the antimicrobial activity of arasertaconazole nitrate [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 5-13-2011
220. NCT01144286. Arasertaconazole nitrate pessaries - dose finding study for the vulvovaginal candidiasis (VVC) treatment. 3-14-2011. 5-13-2011
221. Cassone A, Torosantucci A. Opportunistic fungi and fungal infections: The challenge of a single, general antifungal vaccine. Expert Rev Vaccines 2006;5(6):859-67
222. Casadevall A, Pirofski LA. Polysaccharide-containing conjugate vaccines for fungal diseases. Trends Mol Med 2006;12(1):6-9
223. Law D, Dobb K, Fothergill A, et al. F1-850 - Activity of FG3622 a novel antifungal against Aspergillus spp. and other filamentous fungi [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting. 9-13-2009. 5-14-2011
224. Law D, Fothergill AW, Chen SC, et al. F1-858 - The activity of FG3622 and FG3409 against Scedosporium spp [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-12- 2010. 5-14-2011
225. Law D, Goodwin J, Gould J, et al. F1-853 - Pharmacokinetics of the novel antifungal agent FG3622 in mice and rats [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 9-13-2009. 5-14-2011
226. Warn P, Gould J, Majithiya J, et al. F1-851 - In vivo efficacy of orally dosed FG3622, in murine models of disseminated aspergillosis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 9-13-2009. 5-14-2011
227. Vazquez JA, Vager D, Tunac J. M-1700 - In vitro activity of corifungin: A new water soluble - bioavailable polyene, against clinical isolates of candida species [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 9-14-2009. 5-14-2011
228. Vazquez JA, Vager D, Tunac J. M-1713 - In vitro activity of corifungin, a new water-soluble - bioavailable polyene, against Aspergillus spp. and other medically important fungi [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting; 9-14- 2009. 5-14-2011
229. Stevens DA, Martinez M, Chen V. M-387 - Activity of corifungin (Cori) against endemic fungal pathogens [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-12- 2010. 5-14-2011
230. Miyazaki M, Horii T, Hata K, Watanabe N. F1-840 - In vitro antifungal activity of E1210: A novel antifungal with activity against clinically important yeasts and moulds [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-14-2011
231. Hata K, Miyazaki M, Horii T, Watanabe N. F1-842 - Efficacy of E1210, a new broad-spectrum antifungal, in murine models of oropharyngeal candidiasis, disseminated candidiasis, and pulmonary aspergillosis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
232. Barger A, Fuhst C, Wiedemann B. Pharmacological indices in antibiotic therapy. J Antimicrob Chemother 2003;52(6):893-8
233. Horii T, Okubo M, Miyazaki M, et al. F1-843 - In vivo pharmacodynamic correlates of success for E1210 treatment of disseminated candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
234. Okubo M, Toritsuka N, Horii T, et al. F1-844 - Preclinical pharmacokinetics and toxicology of E1210, a new broad-spectrum antifungal [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
235. Motyl MR, Tan C, Liberator P, et al. F1-847 - MK-3118, an oral enfumafungin with potent in vitro activity against Candida and Aspergillus spp [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2011. 5-15-2011
236. Flattery A, Abruzzo G, Gill C, et al. F1-849 - Evaluation of enfumafungin derivative MK-3118 in two mouse models of disseminated aspergillosis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13- 2010. 5-15-2011
237. Flattery A, Abruzzo G, Gill C, et al. F1-848 - Evaluation of orally active enfumafungin derivative MK-3118 in mouse models of disseminated candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
238. Trucksis M, Garrett G, Heirman I, et al. F1-1975 - A phase I single rising dose study evaluating the safety, tolerability and pharmacokinetics of an oral glucan synthase inhibitor in healthy male volunteers [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-15-2010. 5-15-2011
239. Walker SS, Xu X, Triantafyllou I, et al. Discovery of a novel class of orally active antifungal Beta-(1,3) D glucan synthase inhibitors [abstract]. Human fungal pathogens, la colle sur loup. France; 2011. p. P3-25A
240. Kaeriyama M, Yamashita K, Yamada E, et al. M-383 - In vitro and in vivo efficacy of a novel arylamidine T-2307 against clinical isolates of Aspergillus terreus [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-12-2010. 5-15-2011
241. Mitsuyama J, Nomura N, Hashimoto K, et al. In vitro and in vivo antifungal activities of T-2307, a novel arylamidine. Antimicrob Agents Chemother 2008;52(4):1318-24
242. Fujino N, Takahata M, Suenaga A, et al. M-1080 - Efficacy of a novel arylamidine T-2307 against candida albicans in murine model of oral and esophageal infections [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
243. 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):3630-4
244. Fothergill AW, Rinaldi MG, Hoekstra WJ, et al. F1-850 - The investigational metalloenzyme inhibitors VT-1129 and VT-1161 have potent in vitro activity against Cryptococcus species [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
245. Fothergill AW, Rinaldi MG, Hoekstra WJ, et al. F1-851 - In vitro activity of two metalloenzyme inhibitors compared to caspofungin and fluconazole against a panel of 50 candida species [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13- 2010. 5-15-2011
246. Hoekstra WJ, O'Leary AL, Moore WR, Schotzinger RJ. F1-852 - Novel metalloenzyme inhibitors, VT-1161 and VT-1129, exhibit efficacy and survival benefit in a murine systemic candidiasis model [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
247. Wiederhold NP, Najvar LK, Hoekstra WJ, et al. F1-853 - A novel metalloenzyme inhibitor (VT1129) exhibits efficacy in a murine model of cryptococcal meningitis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
248. Mercer DK, Duncan V, Robertson J, et al. F1-856 - In vitro & in vivo activity of NP339, a candidacidal peptide therapeutic candidate [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting; 9-13-2010. 5-15-2011
249. Dominguez JM, Kelly VA, Kinsman OS, et al. Sordarins: A new class of antifungals with selective inhibition of the protein synthesis elongation cycle in yeasts. Antimicrob Agents Chemother 1998;42(9):2274-8
250. Kamai Y, Kakuta M, Shibayama T, et al. Antifungal activities of R-135853, a sordarin derivative, in experimental candidiasis in mice. Antimicrob Agents Chemother 2005;49(1):52-6
251. Hanadate T, Tomishima M, Shiraishi N, et al. FR290581, a novel sordarin derivative: Synthesis and antifungal activity. Bioorg Med Chem Lett 2009;19(5):1465-8
252. Laverdiere M, Labbe AC, Restieri C, et al. Susceptibility patterns of candida species recovered from Canadian intensive care units. J Crit Care 2007;22(3):245-50
253. Isham N, Ghannoum MA. Determination of MICs of aminocandin for Candida spp. and filamentous fungi. J Clin Microbiol 2006;44(12):4342-4
254. Brzankalski GE, Najvar LK, Wiederhold NP, et al. Evaluation of aminocandin and caspofungin against candida glabrata including isolates with reduced caspofungin susceptibility. J Antimicrob Chemother 2008;62(5):1094-100
255. Ghannoum MA, Kim HG, Long L. Efficacy of aminocandin in the treatment of immunocompetent mice with haematogenously disseminated fluconazole-resistant candidiasis. J Antimicrob Chemother 2007;59(3):556-9
256. Warn PA, Sharp A, Morrissey G, Denning DW. Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of Aspergillus fumigatus. Int J Antimicrob Agents 2010;35(2):146-51
257. Najvar LK, Bocanegra R, Wiederhold NP, et al. Therapeutic and prophylactic efficacy of aminocandin (IP960) against disseminated candidiasis in mice. Clin Microbiol Infect 2008;14(6):595-600
258. Andes D, Marchillo K, Lowther J, et al. In vivo pharmacodynamics of HMR 3270, a glucan synthase inhibitor, in a murine candidiasis model. Antimicrob Agents Chemother 2003;47(4):1187-92
259. Sandage B, Cooper G, Najarian N, Lowther J. Pharmacokinetics and fungicidal activity of aminocandin (HMR3270), a novel echinocandin in healthy volunteers [abstract]. 15th European Congress of Clinical Microbiology and Infectious Diseases. 2005. 5-31-2011
260. Hasenoehrl A, Galic T, Ergovic G, et al. In vitro activity and in vivo efficacy of icofungipen (PLD-118), a novel oral antifungal agent, against the pathogenic yeast Candida albicans. Antimicrob Agents Chemother 2006;50(9):3011-18
261. Ziegelbauer K, Babczinski P, Schonfeld W. Molecular mode of action of the antifungal beta-amino acid BAY 10-8888. Antimicrob Agents Chemother 1998;42(9):2197-205
262. Petraitis V, Petraitiene R, Kelaher AM, et al. Efficacy of PLD-118, a novel inhibitor of candida isoleucyl-tRNA synthetase, against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant C. albicans. Antimicrob Agents Chemother 2004;48(10):3959-67
263. Petraitiene R, Petraitis V, Kelaher AM, et al. Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits. Antimicrob Agents Chemother 2005;49(5):2084-92
264. Parnham MJ, Bogaards JJ, Schrander F, et al. The novel antifungal agent PLD-118 is neither metabolized by liver microsomes nor inhibits cytochrome P450 in vitro. Biopharm Drug Dispos 2005;26(1):27-33
265. Mohr J, Johnson M, Cooper T, et al. Current options in antifungal pharmacotherapy. Pharmacotherapy 2008;28(5):614-45
266. Brockmeyer NH, Ruhnke M, Oreskovic K, Peterson J. Icofungipen (PLD-118) in the treatment of oropharyngeal candidiasis (OPC) in HIV-positive patients [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2004 Annual Meeting. 2004
267. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46(12):1813-21
268. Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European organization for research and treatment of cancer consensus criteria. Clin Infect Dis 2008;47(5):674-83
269. Dodds Ashley E, Lewis R, Lewis JS, et al. Pharmacology of systemic antifungal agents. Clin Infect Dis 2006;43(Suppl 1):s28-39
270. Exjade (deferasirox) tablets for oral suspension prescribing information. 4-1- 2011. 5-28-2011
271. Ruiz-Herrera J, San-Blas G. Chitin synthesis as target for antifungal drugs. Curr Drug Targets Infect Disord 2003;3(1):77-91
272. Bruntner C, Lauer B, Schwarz W, et al. Molecular characterization of co-transcribed genes from streptomyces tendae Tu901 involved in the biosynthesis of the peptidyl moiety of the peptidyl nucleoside antibiotic nikkomycin. Mol Gen Genet 1999;262(1):102-14
273. Acea Biotech. Corifungin. 2011. 5-31-2011
274. Warn PA, Sharp A, Morrissey G, Denning DW. Activity of aminocandin (IP960) compared with amphotericin B and fluconazole in a neutropenic murine model of disseminated infection caused by a fluconazole-resistant strain of Candida tropicalis. J Antimicrob Chemother 2005;56(3):590-3
275. Warn PA, Sharp A, Morrissey G, Denning DW. Activity of aminocandin (IP960; HMR3270) compared with amphotericin B, itraconazole, caspofungin and micafungin in neutropenic murine models of disseminated infection caused by itraconazole-susceptible and -resistant strains of aspergillus fumigatus. Int J Antimicrob Agents 2010;35(2):146-51
276. Vilanova M, Teixeira L, Caramalho I, et al. Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2. Immunology 2004;111(3):334-42
277. Spellberg BJ, Ibrahim AS, Avanesian V, et al. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis 2006;194(2):256-60
278. Lin L, Ibrahim AS, Xu X, et al. Th1-Th17 cells mediate protective adaptive immunity against staphylococcus aureus and candida albicans infection in mice. PLoS Pathog 2009;5(12):e1000703
279. Luo G, Ibrahim AS, Spellberg B, et al. Candida albicans Hyr1p confers resistance to neutrophil killing and is a potential vaccine target. J Infect Dis 2010;201(11):1718-28
280. Bromuro C, Romano M, Chiani P, et al. Beta-glucan-CRM197 conjugates as candidates antifungal vaccines. Vaccine 2010;28(14):2615-23
281. Torosantucci A, Bromuro C, Chiani P, et al. A novel glyco-conjugate vaccine against fungal pathogens. J Exp Med 2005;202(5):597-606
282. Pietrella D, Rachini A, Torosantucci A, et al. A beta-glucan-conjugate vaccine and anti-beta-glucan antibodies are effective against murine vaginal candidiasis as assessed by a novel in vivo imaging technique. Vaccine 2010;28(7):1717-25
283. Torosantucci A, Chiani P, Bromuro C, et al. Protection by anti-beta-glucan antibodies is associated with restricted beta-1,3 glucan binding specificity and inhibition of fungal growth and adherence. PLoS ONE 2009;4(4):e5392
284. Rachini A, Pietrella D, Lupo P, et al. An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect Immun 2007;75(11):5085-94
285. Liu M, Clemons KV, Johansen ME, et al. G1-1656 - Saccharomyces as a vaccine against systemic candidiasis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting. 9-14- 2010. 5-14-2011
286. Stevens DA, Clemons KV, Liu M. Developing a vaccine against aspergillosis. Med Mycol 2011;49(Suppl 1):S170-6
287. Capilla J, Clemons KV, Liu M, et al. Saccharomyces cerevisiae as a vaccine against coccidioidomycosis. Vaccine 2009;27(27):3662-8
288. Liu M, Clemons KV, Bystricky S, Stevens DA. G1-1657 - Glycans and conjugates as vaccines against coccidioidomycosis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2010 Annual Meeting. 9-14-2010. 5-14-2011
289. Liu M, Machova E, Nescakova Z, et al. G1-892 - Vaccination with mannan protects mice against invasive aspergillosis [abstract]. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) 2009 Annual Meeting. 9-13- 2009. 5-14-2011
290. Devi SJ. Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. Vaccine 1996;14(9):841-4