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Newer Systemic Antifungal Agents

Pharmacokinetics, Safety and Efficacy

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Abstract

The past few years have seen the advent of several new antifungal agents, including those of a new class and a new generation of an existing class. Caspofungin, the first available echinocandin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy. In addition, in clinical trials, caspofungin had comparable efficacy to amphotericin B for candidaemia and invasive Candida infections. Caspofungin and two more recently introduced echinocandins, micafungin and anidulafungin, are available as intravenous formulations only and characterised by potent anti-candidal activity, as well as few adverse events and drug interactions.

Voriconazole, the first available second-generation triazole, available in both intravenous and oral formulations, has added a new and improved therapeutic option for primary therapy of invasive aspergillosis and salvage therapy for yeasts and other moulds. In a randomised trial, voriconazole demonstrated superior efficacy and a survival benefit compared with amphotericin B followed by other licensed antifungal therapy. This and data from a noncomparative study led to voriconazole becoming a new standard of therapy for invasive aspergillosis. Voriconazole has several important safety issues, including visual adverse events, hepatic enzyme elevation and skin reactions, as well as a number of drug interactions. Posaconazole, only available orally and requiring dose administration four times daily, shows encouraging efficacy in difficult to treat infections due to zygomycetes. Ravuconazole, available in both intravenous and oral formulations, has broad-spectrum in vitro potency and in vivo efficacy against a wide range of fungal pathogens. Clinical studies are underway.

Despite the advances offered with each of these drugs, the morbidity and mortality associated with invasive fungal infections remains unacceptable, especially for the most at-risk patients. For individuals with severe immunosuppression as a result of chemotherapy, graft-versus-host disease and its therapy, or transplantation, new drugs and strategies are greatly needed.

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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Groll AH, Shah PM, Mentzel C, et al. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J Infect 1996; 33: 23–32

    Article  PubMed  CAS  Google Scholar 

  2. Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 2001; 32: 358–66

    Article  PubMed  CAS  Google Scholar 

  3. McNeil MM, Nash SL, Hajjeh RA, et al. Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001; 33: 641–7

    Article  PubMed  CAS  Google Scholar 

  4. Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis: disease spectrum, treatment practices, and outcomes: I3 Aspergillus Study Group. Medicine (Baltimore) 2000; 79: 250–60

    Article  CAS  Google Scholar 

  5. Anaissie E. Opportunistic mycoses in the immunocompromised host: experience at a cancer center and review. Clin Infect Dis 1992; 14 Suppl. 1: S43–53

    Article  PubMed  Google Scholar 

  6. Walsh TJ, Gonzalez C, Lyman CA, et al. Invasive fungal infections in children: recent advances in diagnosis and treatment. Adv Pediatr Infect Dis 1996; 11: 187–290

    PubMed  CAS  Google Scholar 

  7. Walsh TJ, Hiemenz J, Pizzo PA. Evolving risk factors for invasive fungal infections: all neutropenic patients are not the same. Clin Infect Dis 1994; 18: 793–8

    Article  PubMed  CAS  Google Scholar 

  8. Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am 1996; 10: 365–400

    Article  PubMed  CAS  Google Scholar 

  9. Chiou CC, Groll AH, Walsh TJ. New drugs and novel targets for treatment of invasive fungal infections in patients with cancer. Oncologist 2000; 5: 120–35

    Article  PubMed  CAS  Google Scholar 

  10. Deresinski SC, Stevens DA. Caspofungin. Clin Infect Dis 2003; 36: 1445–57

    Article  PubMed  CAS  Google Scholar 

  11. Current WL, Tang J, Boylan C, et al. Glucan biosynthesis as a target for antifungal: the echinocandin class of antifungal agents. In: Dixon GK, Hollomon DW, editors. Antifungal agents: discovery and mode. Oxford: BIOS Scientific Publishers, 1995: 143–60

    Google Scholar 

  12. Denning DW. Echinocandins and pneumocandins: a new antifungal class with a novel mode of action. J Antimicrob Chemother 1997; 40: 611–4

    Article  PubMed  CAS  Google Scholar 

  13. Walsh TJ. Echinocandins: an advance in the primary treatment of invasive candidiasis. N Engl J Med 2002; 347: 2070–2

    Article  PubMed  Google Scholar 

  14. Bartizal K, Gill CJ, Abruzzo GK, et al. In vitro preclinical evaluation studies with the echinocandin antifungal MK-0991 (L-743,872). Antimicrob Agents Chemother 1997; 41: 2326–32

    PubMed  CAS  Google Scholar 

  15. Vazquez JA, Lynch M, Boikov D, et al. In vitro activity of a new pneumocandin antifungal, L-743,872, against azole-susceptible and -resistant Candida species. Antimicrob Agents Chemother 1997; 41: 1612–4

    PubMed  CAS  Google Scholar 

  16. Espinel-Ingroff A. Comparison of in vitro activities of the new triazole SCH56592 and the echinocandins MK-0991 (L-743,872) and LY303366 against opportunistic filamentous and dimorphic fungi and yeasts. J Clin Microbiol 1998; 36: 2950–6

    PubMed  CAS  Google Scholar 

  17. Letscher-Bru V, Herbrecht R. Caspofungin: the first representative of a new antifungal class. J Antimicrob Chemother 2003; 51: 513–21

    Article  PubMed  CAS  Google Scholar 

  18. Pfaller MA, Diekema DJ, Messer SA, et al. In-vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp, including 157 fluconazole-resistant isolates. Antimicrob Agents Chemother 2003 Mar; 47(3): 1068–71

    Article  PubMed  CAS  Google Scholar 

  19. Arikan S, Lozano-Chiu M, Paetznick V, et al. In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother 2002; 46: 245–7

    Article  PubMed  CAS  Google Scholar 

  20. Kontoyiannis DP, Lewis RE, Osherov N, et al. Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J Antimicrob Chemother 2003; 51: 313–6

    Article  PubMed  CAS  Google Scholar 

  21. Manavathu EK, Alangaden GJ, Chandrasekar PH. Differential activity of triazoles in two-drug combinations with the echinocandin caspofungin against Aspergillus fumigatus. J Antimicrob Chemother 2003; 51: 1423–5

    Article  PubMed  CAS  Google Scholar 

  22. Perea S, Gonzalez G, Fothergill AW, et al. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 2002; 46: 3039–41

    Article  PubMed  CAS  Google Scholar 

  23. Shalit I, Shadkchan Y, Samra Z, et al. In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points. Antimicrob Agents Chemother 2003; 47: 1416–8

    Article  PubMed  CAS  Google Scholar 

  24. Arikan S, Lozano-Chiu M, Paetznick V, et al. In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother 2001; 45: 327–30

    Article  PubMed  CAS  Google Scholar 

  25. Del Poeta M, Schell WA, Perfect JR. In vitro antifungal activity of pneumocandin L-743,872 against a variety of clinically important molds. Antimicrob Agents Chemother 1997; 41: 1835–6

    PubMed  Google Scholar 

  26. Pfaller MA, Marco F, Messer SA, et al. In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi. Diagn Microbiol Infect Dis 1998; 30: 251–5

    Article  PubMed  CAS  Google Scholar 

  27. Abruzzo GK, Flattery AM, Gill CJ, et al. Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis. Antimicrob Agents Chemother 1997; 41: 2333–8

    PubMed  CAS  Google Scholar 

  28. Abruzzo GK, Gill CJ, Flattery AM, et al. Efficacy of the echinocandin caspofungin against disseminated aspergillosis and candidiasis in cyclophosphamide-induced immunosuppressed mice. Antimicrob Agents Chemother 2000; 44: 2310–8

    Article  PubMed  CAS  Google Scholar 

  29. Graybill JR, Bocanegra R, Luther M, et al. Treatment of murine Candida krusei or Candida glabrata infection with L-743,872. Antimicrob Agents Chemother 1997; 41: 1937–9

    PubMed  CAS  Google Scholar 

  30. Graybill JR, Najvar LK, Luther MF, et al. Treatment of murine disseminated candidiasis with L-743,872. Antimicrob Agents Chemother 1997; 41: 1775–7

    PubMed  CAS  Google Scholar 

  31. Ju JY, Polhamus C, Marr KA, et al. Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata-infected p47phox-/-knockout mice. Antimicrob Agents Chemother 2002; 46: 1240–5

    Article  PubMed  CAS  Google Scholar 

  32. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia. Antimicrob Agents Chemother 2002; 46: 12–23

    Article  PubMed  CAS  Google Scholar 

  33. Bowman JC, Hicks PS, Kurtz MB, et al. The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro. Antimicrob Agents Chemother 2002; 46: 3001–12

    Article  PubMed  CAS  Google Scholar 

  34. Kirkpatrick WR, Perea S, Coco BJ, et al. Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002; 46: 2564–8

    Article  PubMed  CAS  Google Scholar 

  35. 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: 1834–43

    Article  PubMed  CAS  Google Scholar 

  36. Gonzalez GM, Najvar LK, Tijerina R, et al. Therapeutic efficacy of caspofungin (CAS) alone and in combination with deoxycholate amphotericin B (DAMB) or liposomal amphotericin B (LAMB) for coccidioidomycosis in a mouse model [abstract no. M-475]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 445

  37. Groll AH, Gea-Banacloche JC, Glasmacher A, et al. Clinical pharmacology of antifungal compounds. Infect Dis Clin North Am 2003; 17: 159–91, ix

    Article  PubMed  Google Scholar 

  38. Hajdu R, Thompson R, Sundelof JG, et al. Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872). Antimicrob Agents Chemother 1997; 41: 2339–44

    PubMed  CAS  Google Scholar 

  39. Cancidas (Caspofungin for intravenous injection), Merck Corporation, NDA 21-227. Background document for Antiviral Drug Products Advisory Committee Meeting, 10 January 2001. Merck Corporation [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3676b1_01.pdf [Accesssed 2004 Jun 1]

  40. Cancidas package insert. Rahway (NJ): Merck Corporation, 2003

  41. Balani SK, Xu X, Arison BH, et al. Metabolites of caspofungin acetate, a potent antifungal agent, in human plasma and urine. Drug Metab Dispos 2000; 28: 1274–8

    PubMed  CAS  Google Scholar 

  42. Stone JA, Holland SD, Wickersham PJ, et al. Single- and multiple-dose pharmacokinetics of caspofungin in healthy men. Antimicrob Agents Chemother 2002; 46: 739–45

    Article  PubMed  CAS  Google Scholar 

  43. Walsh TJ, Adamson PC, Seibel NL, et al. Pharmacokinetics (PK) of caspofungin (CAS) in pediatric patients [abstract no. M-896]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego, 395

  44. Stone JA, Migoya E, Hickey L, et al. Drug interactions between caspofungin and nelfinavir or rifampin [abstract no. A-1605]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 34

  45. Maertens J, Raad I, Petrikkos G, et al. Update of the multicenter noncomparative study of caspofungin (CAS) in adults with invasive aspergillosis (IA) refractory (R) or intolerant (I) to other antifungal agents: analysis of 90 patients [abstract no. M-868]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego

  46. Villanueva A, Arathoon EG, Gotuzzo E, et al. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis 2001; 33: 1529–35

    Article  PubMed  CAS  Google Scholar 

  47. Sora F, Chiusolo P, Piccirillo N, et al. Successful treatment with caspofungin of hepatosplenic candidiasis resistant to liposomal amphotericin B. Clin Infect Dis 2002; 35: 1135–6

    Article  PubMed  Google Scholar 

  48. Mora-Duarte J, Betts R, Rotstein C, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 2002; 347: 2020–9

    Article  PubMed  CAS  Google Scholar 

  49. Walsh T, Sable C, Depauw B, et al. A randomized, double-blind, multicenter trial of caspofungin (CAS) v liposomal amphotericin B (LAMB) for empirical antifungal therapy (EAFRx) of persistently febrile neutropenic (PFN) patients (Pt) [abstract no. M-1761]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 477

  50. Tomishima M, Ohki H, Yamada A, et al. FK463, a novel water-soluble echinocandin lipopeptide: synthesis and antifungal activity. J Antibiot (Tokyo) 1999; 52: 674–6

    Article  CAS  Google Scholar 

  51. Laverdiere M, Hoban D, Restieri C, et al. In vitro activity of three new triazoles and one echinocandin against Candida bloodstream isolates from cancer patients. J Antimicrob Chemother 2002; 50: 119–23

    Article  PubMed  CAS  Google Scholar 

  52. Mikamo H, Sato Y, Tamaya T. In vitro antifungal activity of FK463, a new water-soluble echinocandin-like lipopeptide. J Antimicrob Chemother 2000; 46: 485–7

    Article  PubMed  CAS  Google Scholar 

  53. Nakai T, Uno J, Otomo K, et al. In vitro activity of FK463, a novel lipopeptide antifungal agent, against a variety of clinically important molds. Chemotherapy 2002; 48: 78–81

    Article  PubMed  CAS  Google Scholar 

  54. Stevens DA. Susceptibility to micafungin of isolates from clinical trials [abstract no. M-1520]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego

  55. Tawara S, Ikeda F, Maki K, et al. In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi. Antimicrob Agents Chemother 2000; 44: 57–62

    Article  PubMed  CAS  Google Scholar 

  56. Nakai T, Uno J, Ikeda F, et al. In vitro antifungal activity of micafungin (FK463) against dimorphic fungi: comparison of yeast-like and mycelial forms. Antimicrob Agents Chemother 2003; 47: 1376–81

    Article  PubMed  CAS  Google Scholar 

  57. O’Shaughnessy EM, Peter J, Walsh TJ. In vitro additive and synergistic effect of two echinocandins, caspofungin and micafungin with voriconazole against Aspergillus fumigatus [abstract no. M-856]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego, 385

  58. Ghannoum MA, Isham N, Sheehan D. In vitro evaluation of voriconazole in combination with antifungal agents against filamentous fungi [abstract no. M-855]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego, 385

  59. Chiou CC, Mavrogiorgos N, Tillem E, et al. Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus. Antimicrob Agents Chemother 2001; 45: 3310–21

    Article  PubMed  CAS  Google Scholar 

  60. Ito M, Nozu R, Kuramochi T, et al. Prophylactic effect of FK463, a novel antifungal lipopeptide, against Pneumocystis carinii infection in mice. Antimicrob Agents Chemother 2000; 44: 2259–62

    Article  PubMed  CAS  Google Scholar 

  61. Maesaki S, Hossain MA, Miyazaki Y, et al. Efficacy of FK463, a (l,3)-beta-D-glucan synthase inhibitor, in disseminated azole-resistant Candida albicans infection in mice. Antimicrob Agents Chemother 2000; 44: 1728–30

    Article  PubMed  CAS  Google Scholar 

  62. Matsumoto S, Wakai Y, Nakai T, et al. Efficacy of FK463, a new lipopeptide antifungal agent, in mouse models of pulmonary aspergillosis. Antimicrob Agents Chemother 2000; 44: 619–21

    Article  PubMed  CAS  Google Scholar 

  63. Petraitis V, Petraitiene R, Groll AH, et al. Comparative antifungal activities and plasma pharmacokinetics of micafungin (FK463) against disseminated candidiasis and invasive pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother 2002; 46: 1857–69

    Article  PubMed  CAS  Google Scholar 

  64. Warn PA, Morrissey G, Morrissey J, et al. Activity of micafungin (FK463) against an itraconazole-resistant strain of Aspergillus fumigatus and a strain of Aspergillus terreus demonstrating in vivo resistance to amphotericin B. J Antimicrob Chemother 2003; 51: 913–9

    Article  PubMed  CAS  Google Scholar 

  65. Petraitis V, Petraitiene R, Groll AH, et al. Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits. Antimicrob Agents Chemother 1998; 42: 2898–905

    PubMed  CAS  Google Scholar 

  66. Luque JC, Clemons KV, Stevens DA. Efficacy of micafungin alone or in combination against systemic murine aspergillosis. Antimicrob Agents Chemother 2003; 47: 1452–5

    Article  PubMed  CAS  Google Scholar 

  67. Groll AH, Gullick BM, Petraitiene R, et al. Compartmental pharmacokinetics of the antifungal echinocandin caspofungin (MK-0991) in rabbits. Antimicrob Agents Chemother 2001; 45: 596–600

    Article  PubMed  CAS  Google Scholar 

  68. Groll AH, Mickiene D, Petraitis V, et al. Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits. Antimicrob Agents Chemother 2001; 45: 3322–7

    Article  PubMed  CAS  Google Scholar 

  69. Seibel N, Schwartz C, Arrieta A, et al. A phase 1 study to determine the safety and pharmacokinetics (PK) of FK463 (echinocandin) in febrile neutropenic pediatric patients [abstract no. 18]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 1

  70. Townsend R, Herbert M, Dessimoz M, et al. Pharmacokinetics of micafungin, an echinocandin antifungal, in subjects with modrate hepatic dysfunction [abstract no. 16]. 31st Annual Meeting of the American College of Clinical Pharmacology; 2002 Sep 21–23; San Francisco

  71. Pettengell K, Mynhard J, Kluyts T, et al. A multicenter study of the echinocandin antifungal FK463 for the treatment of esophageal candidiasis in HIV positive patients [abstract no. 1104]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto, 371

  72. Suleiman J, Delia Negra M, Llanos-Cuentas A, et al. Open label study of micafungin in the treatment of esophageal candidiasis (EC) [abstract no. M-892]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego, 394

  73. De Wet NTE, Llanos-Cuentas A, Suleiman H, et al. Micafungin (FK463) dose response and comparison with fluconazole in oesophageal candidiasis [abstract no. M-1754]. 43rd Inter-science Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 476

  74. Kohno S, Masaoka T, Yamaguchi H. A multicenter, open-label clinical study of FK463 in patients with deep mycosis in Japan [abstract no. J-834]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago, 384

  75. Kontoyiannis D, Buell D, Frisbee-Hume S, et al. Initial experience with FK463 for the treatment of candidemia in cancer patients [abstract no. J-1629]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago, 394

  76. Van Burik J, Ratanatharathorn V, Lipton J, et al. Randomized, double-blind trial of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplant (HSCT), NIAID/BAMSG Protocol 46 [abstract no. M-1238]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego

  77. Cuenca-Estrella M, Mellado E, Diaz-Guerra TM, et al. Susceptibility of fluconazole-resistant clinical isolates of Candida spp. to echinocandin LY303366, itraconazole and amphotericin B. J Antimicrob Chemother 2000; 46: 475–7

    CAS  Google Scholar 

  78. Marco F, Pfaller MA, Messer SA, et al. Activity of MK-0991 (L-743,872), a new echinocandin, compared with those of LY303366 and four other antifungal agents tested against blood stream isolates of Candida spp. Diagn Microbiol Infect Dis 1998; 32: 33–7

    Article  PubMed  CAS  Google Scholar 

  79. Moore CB, Oakley KL, Denning DW. In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species. Clin Microbiol Infect 2001; 7: 11–6

    Article  PubMed  CAS  Google Scholar 

  80. Oakley KL, Moore CB, Denning DW. In vitro activity of the echinocandin antifungal agent LY303,366 in comparison with itraconazole and amphotericin B against Aspergillus spp. Antimicrob Agents Chemother 1998; 42: 2726–30

    PubMed  CAS  Google Scholar 

  81. Zhanel GG, Karlowsky JA, Harding GA, et al. In vitro activity of a new semisynthetic echinocandin, LY-303366, against systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species. Antimicrob Agents Chemother 1997; 41: 863–5

    PubMed  CAS  Google Scholar 

  82. Philip A, Odabasi Z, Rodriguez JR, et al. In vitro synergy testing of andulafungin (ANID) with itraconzole (ITR) and voriconazole (VOR) against Aspergillus spp. and Fusarium spp. [abstract no. M-988]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 452

  83. Petraitis V, Petraitiene R, Groll AH, et al. Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis. Antimicrob Agents Chemother 2001; 45: 471–9

    Article  PubMed  CAS  Google Scholar 

  84. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal activity of LY303366, a novel echinocandin B, in experimental disseminated candidiasis in rabbits. Antimicrob Agents Chemother 1999; 43: 2148–55

    PubMed  CAS  Google Scholar 

  85. Verweij PE, Oakley KL, Morrissey J, et al. Efficacy of LY303366 against amphotericin B-susceptible and -resistant Aspergillus fumigatus in a murine model of invasive aspergillosis. Antimicrob Agents Chemother 1998; 42: 873–8

    PubMed  CAS  Google Scholar 

  86. Roberts J, Schock K, Marino S, et al. 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: 3381–8

    Article  PubMed  CAS  Google Scholar 

  87. Groll AH, Mickiene D, Petraitiene R, et al. Pharmacokinetic and pharmacodynamic modeling of anidulafungin (LY303366): reappraisal of its efficacy in neutropenic animal models of opportunistic mycoses using optimal plasma sampling. Antimicrob Agents Chemother 2001; 45: 2845–55

    Article  PubMed  CAS  Google Scholar 

  88. Rajman I, Desante K, Hatcher B, et al. LY 303366 single dose pharmacokinetics and safety in healthy male volunteers [abstract no. F-74]. 36th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1997 Sep 15–18; Washington, DC, 158

  89. Dowell J, Knebel W, Ludden T, et al. A population pharmacokinetic analysis of anidulafungin [abstract no. A-1575]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 31

  90. Krause DS, Henkel T, Goldstein BP, et al. Anidulafungin (ANID) vs. fluconazole (FLU) in esophageal candidiasis (EC): a phase 3, randomized, double-blind, multicenter trial [abstract no. M-1760]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 477

  91. Schranz JA, Krause D, Goldstein BP, et al. Efficacy of Anidulafungin (ANID) for the treatment of candidemia [abstract no. M-971]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 448

  92. Vfend (Voriconazole for intravenous injection), NDA 21-267, Background Document for Antiviral Drug Products Advisory Committee Meeting, 4 October 2001. Pfizer Inc. [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/01/briefing/3792b2_01_Pfizer.pdf [Accesssed 2004 Jun 1]

  93. Barry AL, Pfaller MA, Brown SD, et al. Quality control limits for broth microdilution susceptibility tests of ten antifungal agents. J Clin Microbiol 2000; 38: 3457–9

    PubMed  CAS  Google Scholar 

  94. Perea S, Fothergill AW, Sutton DA, et al. Comparison of in vitro activities of voriconazole and five established antifungal agents against different species of dermatophytes using a broth macrodilution method. J Clin Microbiol 2001; 39: 385–8

    Article  PubMed  CAS  Google Scholar 

  95. Pfaller MA, Diekema DJ, Messer SA, et al. In vitro activities of voriconazole, posaconazole, and four licensed systemic antifungal agents against Candida species infrequently isolated from blood. J Clin Microbiol 2003; 41: 78–83

    Article  PubMed  CAS  Google Scholar 

  96. Pfaller MA, Messer SA, Hollis RJ, et al. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob Agents Chemother 2002; 46: 1032–7

    CAS  Google Scholar 

  97. Dannaoui E, Meletiadis J, Mouton JW, et al. In vitro susceptibilities of zygomycetes to conventional and new antifungals. J Antimicrob Chemother 2003; 51: 45–52

    Article  PubMed  CAS  Google Scholar 

  98. Espinel-Ingroff A, Boyle K, Sheehan DJ. In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia 2001; 150: 101–15

    Article  PubMed  CAS  Google Scholar 

  99. Sun QN, Fothergill AW, McCarthy DI, et al. In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes. Antimicrob Agents Chemother 2002; 46: 1581–2

    Article  PubMed  CAS  Google Scholar 

  100. Espinel-Ingroff A. Germinated and nongerminated conidial suspensions for testing of susceptibilities of Aspergillus spp. to amphotericin B, itraconazole, posaconazole, ravuconazole, and voriconazole. Antimicrob Agents Chemother 2001; 45: 605–7

    Article  CAS  Google Scholar 

  101. Espinel-Ingroff A. In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J Clin Microbiol 2001; 39: 954–8

    Article  PubMed  CAS  Google Scholar 

  102. Johnson EM, Szekely A, Warnock DW. In-vitro activity of voriconazole, itraconazole and amphotericin B against filamentous fungi. J Antimicrob Chemother 1998; 42: 741–5

    Article  PubMed  CAS  Google Scholar 

  103. Lass-Florl C, Nagl M, Speth C, et al. Studies of in vitro activities of voriconazole and itraconazole against Aspergillus hyphae using viability staining. Antimicrob Agents Chemother 2001; 45: 124–8

    Article  PubMed  CAS  Google Scholar 

  104. Manavathu EK, Cutright JL, Chandrasekar PH. Organism-dependent fungicidal activities of azoles. Antimicrob Agents Chemother 1998; 42: 3018–21

    PubMed  CAS  Google Scholar 

  105. Sutton DA, Sanche SE, Revankar SG, et al. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, with a head-to-head comparison to voriconazole. J Clin Microbiol 1999; 37: 2343–5

    PubMed  CAS  Google Scholar 

  106. Walsh TJ, Lee J, Dismukes WE. Decisions about voriconazole versus liposomal amphotericin B [letter]. N Engl J Med 2002; 346: 1499; author reply 1499

    Article  PubMed  Google Scholar 

  107. Manavathu E, Krishnan S, Chandrasekar P. A comparative study of the fungicidal activity of voriconazole and amphotericin B against Aspergillus fumigatus hyphae [abstract no. M-1250]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 472

  108. Ruhnke M, Schmidt-Westhausen A, Trautmann M. In vitro activities of voriconazole (UK-109,496) against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1997; 41: 575–7

    PubMed  CAS  Google Scholar 

  109. Pfaller MA, Diekema DJ, Jones RN, et al. Trends in antifungal susceptibility of Candida spp. iisolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000. J Clin Microbiol 2002; 40: 852–6

    Article  PubMed  CAS  Google Scholar 

  110. Pfaller MA, Messer SA, Houston A, et al. Evaluation of the Etest method for determining voriconazole susceptibilities of 312 clinical isolates of Candida species by using three different agar media. J Clin Microbiol 2000; 38: 3715–7

    PubMed  CAS  Google Scholar 

  111. Sanati H, Belanger P, Fratti R, et al. A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in Candida albicans and Candida krusei. Antimicrob Agents Chemother 1997; 41: 2492–6

    PubMed  CAS  Google Scholar 

  112. Li RK, Ciblak MA, Nordoff N, et al. In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis, and Histoplasma capsulatum. Antimicrob Agents Chemother 2000; 44: 1734–6

    Article  PubMed  CAS  Google Scholar 

  113. Carrillo AJ, Guarro J. In vitro activities of four novel triazoles against Scedosporium spp. Antimicrob Agents Chemother 2001; 45: 2151–3

    Article  PubMed  CAS  Google Scholar 

  114. Cuenca-Estrella M, Ruiz-Diez B, Martinez-Suarez JV, et al. Comparative in-vitro activity of voriconazole (UK-109,496) and six other antifungal agents against clinical isolates of Scedosporium prolificans and Scedosporium apiospermum. J Antimicrob Chemother 1999; 43: 149–51

    Article  PubMed  CAS  Google Scholar 

  115. Meletiadis J, Meis JF, Mouton JW, et al. In vitro activities of new and conventional antifungal agents against clinical Scedosporium isolates. Antimicrob Agents Chemother 2002; 46: 62–8

    Article  PubMed  CAS  Google Scholar 

  116. Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, et al. In vitro activities of investigational triazoles against Fusarium species: effects of inoculum size and incubation time on broth microdilution susceptibility test results. Antimicrob Agents Chemother 2002; 46: 3298–300

    Article  PubMed  CAS  Google Scholar 

  117. Paphitou NI, Ostrosky-Zeichner L, Paetznick VL, et al. In vitro antifungal susceptibilities of Trichosporon species. Antimicrob Agents Chemother 2002; 46: 1144–6

    Article  PubMed  CAS  Google Scholar 

  118. Martin MV, Yates J, Hitchcock CA. Comparison of voriconazole (UK-109,496) and itraconazole in prevention and treatment of Aspergillus fumigatus endocarditis in guinea pigs. Antimicrob Agents Chemother 1997; 41: 13–6

    PubMed  CAS  Google Scholar 

  119. Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis. Antimicrob Agents Chemother 2000; 44: 2865–8

    Article  PubMed  CAS  Google Scholar 

  120. Ghannoum MA, Okogbule-Wonodi I, Bhat N, et al. Antifungal activity of voriconazole (UK-109,496), fluconazole and amphotericin B against hematogenous Candida krusei infection in neutropenic guinea pig model. J Chemother 1999; 11: 34–9

    PubMed  CAS  Google Scholar 

  121. Groll AH, Lyman CA, Petraitiene R, et al. Differential intrapulmonary disposition of voriconazole and liposomal amphotericin B in noninfected rabbits [abstract no. M-1256]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 474

  122. 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: 2546–53

    Article  PubMed  CAS  Google Scholar 

  123. Walsh TJ, Lutsar I, Driscoll T, et al. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J 2002; 21: 240–8

    Article  PubMed  Google Scholar 

  124. Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 2003; 36: 1122–31

    Article  PubMed  CAS  Google Scholar 

  125. Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002; 347: 408–15

    Article  PubMed  CAS  Google Scholar 

  126. Vfend package insert. New York: Pfizer Inc., 2003

  127. Chow L, Brown NE, Kunimoto D. An unusual case of pulmonary invasive aspergillosis and aspergilloma cured with voriconazole in a patient with cystic fibrosis. Clin Infect Dis 2002; 35: el06–10

    Article  Google Scholar 

  128. Denning DW, Ribaud P, Milpied N, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002; 34: 563–71

    Article  PubMed  CAS  Google Scholar 

  129. Ally R, Schurmann D, Kreisel W, et al. A randomized, doubleblind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis 2001; 33: 1447–54

    Article  PubMed  CAS  Google Scholar 

  130. Ostrosky-Zeichner L, Oude Lashof AM, Kullberg B-J, et al. Voriconazole (VOR) salvage treatment of invasive candidiasis (IC): experience from open-label protocols [abstract no. 352]. 40th Annual Meeting of the Infectious Diseases Society of America; 2002 Oct 24–27; Chicago

  131. Girmenia C, Luzi G, Monaco M, et al. Use of voriconazole in treatment of Scedosporium apiospermum infection: case report. J Clin Microbiol 1998; 36: 1436–8

    PubMed  CAS  Google Scholar 

  132. Gosbell IB, Toumasatos V, Yong J, et al. Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole plus terbinafine, without the need for radical surgery. Mycoses 2003; 46: 233–6

    Article  PubMed  CAS  Google Scholar 

  133. Jabado N, Casanova JL, Haddad E, et al. Invasive pulmonary infection due to Scedosporium apiospermum in two children with chronic granulomatous disease. Clin Infect Dis 1998; 27: 1437–41

    Article  PubMed  CAS  Google Scholar 

  134. Munoz P, Marin M, Tornero P, et al. Successful outcome of Scedosporium apiospermum disseminated infection treated with voriconazole in a patient receiving corticosteroid therapy. Clin Infect Dis 2000; 31: 1499–501

    Article  PubMed  CAS  Google Scholar 

  135. Nesky MA, McDougal EC, Peacock Jr JE. Pseudallescheria boydii brain abscess successfully treated with voriconazole and surgical drainage: case report and literature review of central nervous system pseudallescheriasis. Clin Infect Dis 2000; 31: 673–7

    Article  PubMed  CAS  Google Scholar 

  136. Poza G, Montoya J, Redondo C, et al. Meningitis caused by Pseudallescheria boydii treated with voriconazole. Clin Infect Dis 2000; 30: 981–2

    Article  PubMed  CAS  Google Scholar 

  137. Martin CA, Roberts S, Greenberg RN. Voriconazole treatment of disseminated paecilomyces infection in a patient with acquired immunodeficiency syndrome. Clin Infect Dis 2002; 35: e78–81

    Article  PubMed  Google Scholar 

  138. Consigny S, Dhedin N, Datry A, et al. Successsful voriconazole treatment of disseminated fusarium infection in an immunocompromised patient. Clin Infect Dis 2003; 37: 311–3

    Article  PubMed  Google Scholar 

  139. Reis A, Sundmacher R, Tintelnot K, et al. Successful treatment of ocular invasive mould infection (fusariosis) with the new antifungal agent voriconazole. Br J Ophthalmol 2000; 84: 932–3

    Article  PubMed  CAS  Google Scholar 

  140. Cortez KJ, Walsh TJ, Bennett JE. Successful treatment of coccidioidal meningitis with voriconazole. Clin Infect Dis 2003; 36: 1619–22

    Article  PubMed  CAS  Google Scholar 

  141. Schlamm H, Supparatpinyo K. Voriconazole as therapy for sytemic infections caused by Penicillium marneffei in patients with HIV infection [abstract no. M963]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 446

  142. Lewis JS, Boucher HW, Lubowski T, et al. Economic advantage of voriconazole (VRC) for primary treatment of invasive aspergillosis compared to conventional amphotericin B (CAB) [abstract no. A-1359]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 26

  143. Gea-Banacloche JC, Peter J, Bishop M, et al. Successful treatment of invasive aspergillosis with the combination of voriconazole and casporfungin: correlation with in vitro interactions [abstract no. M-1759]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 477

  144. Steinbach WJ, Benjamin Jr DK, Kontoyiannis DP, et al. Invasive aspergillosis (IA) caused by Aspergillus terreus: multicenter retrospective analysis of 87 cases [abstract no. M-1753]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 475

  145. Troke P, Schwartz S, Ruhnke M, et al. Voriconazole (VRC) therapy (Rx) in 86 patients (pts) with CNS aspergillosis (CNSA): a retrospective analysis [abstract no. M-1755]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 476

  146. Lortholary O, Mouas-Dupuy H, Dupont B, et al. Voriconazole (VCZ) for bone aspergillosis (BA): a worldwide experience of 19 cases [abstract no. M-979]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 450

  147. Walsh TJ, Pappas P, Winston DJ, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002; 346: 225–34

    Article  PubMed  CAS  Google Scholar 

  148. Bennett JE, Powers J, Walsh T, et al. Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 2003; 36: S117–22

    Article  PubMed  Google Scholar 

  149. Powers JH, Dixon CA, Goldberger MJ. Voriconazole versus liposomal amphotericin B in patients with neutropenia and persistent fever. N Engl J Med 2002; 346: 289–90

    Article  PubMed  Google Scholar 

  150. Ullmann AJ, Heussel CP, Cornely OA. Voriconazole versus liposomal amphotericin B for empirical antifungal therapy. N Engl J Med 2002; 346: 1745–7

    Article  PubMed  Google Scholar 

  151. Marty FM, Cosimi LA, Baden LR. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 2004; 350: 950–2

    Article  PubMed  CAS  Google Scholar 

  152. Walsh TJ, Groll A, Hiemenz J, et al. Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 2004; 10 Suppl. 1: 48–66

    Article  PubMed  Google Scholar 

  153. Tan K, Brayshaw N, Oakes M. Investigation of the relationship between plasma voriconazole (V) concentrations and liver function test (LFT) abnormalities in therapeutic trials [abstract no. A-18]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago, 2

  154. McHale M, Rubin RH, Smith M, et al. Voriconazole (V) use in liver transplant (LT) recipients with invasive fungal infection [abstract no. M-1758]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 477

  155. Swift AC, Denning DW. Skull base osteitis following fungal sinusitis. J Laryngol Otol 1998; 112: 92–7

    Article  PubMed  CAS  Google Scholar 

  156. Barchiesi F, Arzeni D, Camiletti V, et al. In vitro activity of posaconazole against clinical isolates of dermatophytes. J Clin Microbiol 2001; 39: 4208–9

    Article  PubMed  CAS  Google Scholar 

  157. Gonzalez GM, Tijerina R, Najvar LK, et al. In vitro and in vivo activities of posaconazole against Coccidioides immitis. Antimicrob Agents Chemother 2002; 46: 1352–6

    Article  PubMed  CAS  Google Scholar 

  158. Gonzalez GM, Tijerina R, Najvar LK, et al. Activity of posaconazole against Pseudallescheria boydii: in vitro and in vivo assays. Antimicrob Agents Chemother 2003; 47: 1436–8

    Article  PubMed  CAS  Google Scholar 

  159. Nucci M, Akiti T, Barreiros G, et al. Nosocomial fungemia due to Exophiala jeanselmei var. jeanselmei and a Rhinocladiella species: newly described causes of bloodstream infection. J Clin Microbiol 2001; 39: 514–8

    Article  PubMed  CAS  Google Scholar 

  160. Pfaller MA, Messer SA, Hollis RJ, et al. In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3,685 clinical isolates of Candida spp. and Cryptococcus neoformans. Antimicrob Agents Chemother 2001; 45: 2862–4

    Article  PubMed  CAS  Google Scholar 

  161. Uchida K, Yokota N, Yamaguchi H. In vitro antifungal activity of posaconazole against various pathogenic fungi. Int J Antimicrob Agents 2001; 18: 167–72

    Article  PubMed  CAS  Google Scholar 

  162. Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis. Antimicrob Agents Chemother 2000; 44: 780–2

    Article  PubMed  CAS  Google Scholar 

  163. Petraitiene R, Petraitis V, Groll AH, et al. Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. Antimicrob Agents Chemother 2001; 45: 857–69

    Article  PubMed  CAS  Google Scholar 

  164. Walsh TJ, Petraitis V, Petraitiene R, et al. Experimental pulmonary aspergillosis due to aspergillus terreus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J Infect Dis 2003; 188: 305–19

    Article  PubMed  CAS  Google Scholar 

  165. Sabatelli F. In vitro and in vivo interaction of posaconazole (POS) and caspofungin (CSP) against aspergillus [abstract no. M-990]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 453

  166. Sun QN, Najvar LK, Bocanegra R, et al. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother 2002; 46: 2310–2

    Article  PubMed  CAS  Google Scholar 

  167. Connolly P, Wheat LJ, Schnizlein-Bick C, et al. Comparison of a new triazole, posaconazole, with itraconazole and amphotericin B for treatment of histoplasmosis following pulmonary challenge in immunocompromised mice. Antimicrob Agents Chemother 2000; 44: 2604–8

    Article  PubMed  CAS  Google Scholar 

  168. Najvar LK, Sun QN, Bocanegra R, et al. Posaconazole (POSA) treatment of experimental zygomycosis [abstract no. J-1616]. 41st Interscience Conference on Antimicrobial Agents and Chemotherapy; 2001 Dec 16–19; Chicago

  169. Ezzet F, Wexler D, Courtney R, et al. The pharmacokinetic properties of posaconazole in faster healthy subjects: basis for clinical dosage recommendations [abstract no. A-1393]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2002 Sep 27–30; San Diego

  170. Courtney R, Pai S, Laughlin M, et al. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob Agents Chemother 2003; 47: 2788–95

    Article  PubMed  CAS  Google Scholar 

  171. Sponsel WE, Graybill JR, Nevarez HL, et al. Ocular and systemic posaconazole (SCH-56592) treatment of invasive Fusarium solani keratitis and endophthalmitis. Br J Ophthalmol 2002; 86: 829–30

    Article  PubMed  CAS  Google Scholar 

  172. Courtney R, Sansone A, Calzetta A, et al. The effect of nutritional supplement (Boost Plus) on the oral bioavailability of posaconazole [abstract no. A-1604]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 33

  173. Sansone A, Belle D, Statkevich P, et al. Effect of posaconazole on the pharmacokinetics of tacrolimus in healthy volunteers [abstract no. A-1603]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 33

  174. Nieto L, Northland R, Pittsuttithum P, et al. Posaconazole equivalent to fluconazole in the treatment of oropharyngeal candidiasis [abstract no. 1108]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto

  175. Vazquez J, Northland R, Miller S, et al. Posaconazole compared to fluconazole for oral candidiasis in HIV-positive patients [abstract no. 1107]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto

  176. Hachem R, Raad II, Afif CM, et al. An open, non-comparative multicenter study to evaluate efficacy and safety of posaconazole (SCH 56592) in the treatment of invasive fungal infections (IFI) refractory (R) to or intolerant (I) to standard therapy (ST) [abstract no. 1109]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2000 Sep 17–20; Toronto

  177. Ullmann A, Comely OA, Burchardt A, et al. Safety and efficacy of posaconazole (POS) in a pharmacokinetic study in patients with febrile neutropenia (FN) or refractory invasive fungal infections (rIFI) [abstract no. M-1257]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 474

  178. Catanzaro A, Cloud G, Stevens D, et al. Safety and tolerance of posaconazole (SCH 56592) in patients with nonmeningeal disseminated coccidioidomycosis [abstract no. 1417]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2000 Sep 17–20; Toronto

  179. Pitisuttithum P, Gaona-Flores V, Negroni R, et al. Efficacy of posaconazole (POS) in treatment of central nervous system (CNS) fungal infections: results of an open-label study [abstract no. M-978]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 450

  180. Greenberg R, Anstead G, Herbrecht R, et al. Posaconazole (POS) experience in the treatment of zygomycosis [abstract no. M-1757]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 476

  181. Segal B, Barnhart LA, Anderson VL, et al. Posaconazole as salvage therapy in patients with chronic granulomatous disease (CGD) with invasive filamentous fungal infection (IFFI) [abstract no. M-1756]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 476

  182. Restrepo A, Clark B, Graham D, et al. Treatment of histoplasmosis with posaconazole [abstract no. M-973]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 449

  183. Herbrecht R, Letscher-Bru V, Fohrer C, et al. Acremonium strictum pulmonary infection in a leukemic patient successfully treated with posaconazole after failure of amphotericin B. Eur J Clin Microbiol Infect Dis 2002; 21: 814–7

    Article  PubMed  CAS  Google Scholar 

  184. Mellinghoff IK, Winston DJ, Mukwaya G, et al. Treatment of Scedosporium apiospermum brain abscesses with posaconazole. Clin Infect Dis 2002; 34: 1648–50

    Article  PubMed  Google Scholar 

  185. Tobon AM, Arango M, Fernandez D, et al. Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis 2003; 36: 1488–91

    Article  PubMed  Google Scholar 

  186. Negroni R, Tobon A, Bustamante A, et al. Posaconazole (POS) treatment of mycetroma and chromoblastomycosis [abstract no. M-976]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 449

  187. Fung-Tomc JC, White TC, Minassian B, et al. In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole. Diagn Microbiol Infect Dis 1999; 35: 163–7

    Article  PubMed  CAS  Google Scholar 

  188. Moore CB, Walls CM, Denning DW. In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B. Antimicrob Agents Chemother 2000; 44: 441–3

    Article  PubMed  CAS  Google Scholar 

  189. Pfaller MA, Messer SA, Gee S, et al. In vitro susceptibilities of Candida dubliniensis isolates tested against the new triazole and echinocandin antifungal agents. J Clin Microbiol 1999; 37: 870–2

    PubMed  CAS  Google Scholar 

  190. Pfaller MA, Messer SA, Hollis RJ, et al. In vitro susceptibilities of Candida bloodstream isolates to the new triazole antifungal agents BMS-207147, Sch 56592, and voriconazole. Antimicrob Agents Chemother 1998; 42: 3242–4

    PubMed  CAS  Google Scholar 

  191. Yamazumi T, Pfaller MA, Messer SA, et al. In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother 2000; 44: 2883–6

    Article  PubMed  CAS  Google Scholar 

  192. Clemons KV, Stevens DA. Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice. Antimicrob Agents Chemother 2001; 45: 3433–6

    Article  PubMed  CAS  Google Scholar 

  193. 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: 2243–7

    PubMed  CAS  Google Scholar 

  194. Kirkpatrick WR, Perea S, Coco BJ, et al. Efficacy of ravueonazole (BMS-207147) in aguinea pig model of disseminated aspergillosis. J Antimicrob Chemother 2002; 49: 353–7

    Article  PubMed  CAS  Google Scholar 

  195. Petraitiene R, Petraitis V, Kelaher AM, et al. Expression of galactomanna antigen in bronchoalveolar lavage fluid of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits [abstract no. M-370]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 434

  196. Grasela DM, Olsen SJ, Mummaneni V, et al. Ravueonazole: multiple ascending oral dose study in healthy subjects [abstract no. 839]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 2000 Sep 17–20; Toronto

  197. Olsen SJ, Mummaneni V, Rolan P, et al. Ravueonazole single ascending oral dose study in healthy subjects [abstract no. 838]. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2000 Sep 17–20; Toronto

  198. Bello A, Russo R, Grasela D, et al. Pharmacokinetics of intravenous BMS-379224 (pro-drug of ravueonazole) in healthy male subjects [abstract no. A-1567]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Abstracts, American Society for Microbiology; 2003 Sep 14–17; Chicago, 29

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Boucher, H.W., Groll, A.H., Chiou, C.C. et al. Newer Systemic Antifungal Agents. Drugs 64, 1997–2020 (2004). https://doi.org/10.2165/00003495-200464180-00001

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