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Chapter 31 : Azoles

Authors: Raoul Herbrecht1, Yasmine Nivoix2
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Affiliations: 1: Dept. of Oncology and Hematology, Hôpital de Hautepierre, 67098 Strasbourg, France; 2: Dept. of Pharmacy and Pharmacology, Hôpital de Hautepierre, 67098 Strasbourg, France
Content Type: Monograph
Publication Year: 2009

Category: Clinical Microbiology; Fungi and Fungal Pathogenesis

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Abstract:

This chapter focuses on itraconazole, voriconazole, posaconazole, ravuconazole, isavuconazole, albaconazole and their role in treating invasive aspergillosis. In a study it was found that patients receiving itraconazole more often had an increase in bilirubin, and this led to the approval of itraconazole for empiric therapy. Metabolism of voriconazole takes place in the liver via the hepatic CYP isoenzymes CYP3A4, CYP2C19, and CYP2C9. Three major and five minor metabolites have been identified which are eliminated within 48 h in the urine and feces. The major metabolite is voriconazole N-oxide, which represents approximately 72% of the metabolites in plasma. The major enzyme involved in the metabolism of voriconazole is CYP2C19, and this enzyme exhibits genetic polymorphism. Several case reports or short series have identified breakthrough fungal infections in patients receiving voriconazole. Posaconazole is an extended-spectrum triazole that is currently only available as an oral suspension. Importantly, the spectrum of activity is extended to Zygomycetes, and clinical trials have shown efficacy of posaconazole in invasive zygomycosis. The large variations in itraconazole, voriconazole, or posaconazole serum levels may be associated with decreased efficacy, increased toxicity, or occurrence of breakthrough infections. Itraconazole serum levels should be monitored in all patients treated with itraconazole capsules for a prolonged period for invasive fungal infections such as aspergillosis or histoplasmosis. Early identification of patients having very low serum drug levels and with low response rates, allows the switch to another therapy to increase the probability of efficacy of the antifungal treatment.

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31

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Fungal Infections
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Antifungal Azoles
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Antifungal Agents
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References

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1. Ahmad, S. R.,, S. J. Singer, and, B. G. Leissa. 2001. Congestive heart failure associated with itraconazole. Lancet 357: 1766– 1767.
2. Alexander, B. D.,, W. A. Schell,, J. L. Miller,, G. D. Long, and, J. R. Perfect. 2005. Candida glabrata fungemia in transplant patients receiving voriconazole after fluconazole. Transplantation 80: 868– 871.
3. Almyroudis, N. G,, D. A. Sutton,, A. W. Fothergill,, M. G. Rinaldi, and, S. Kusne. 2007. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Anti-microb. Agents Chemother. 51: 2587– 2590.
4. Andes, D.,, K. Marchillo,, T. Stamstad, and, R. Conklin. 2003. In vivo pharmacodynamics of a new triazole, ravuconazole, in a murine can-didiasis model. Antimicrob. Agents Chemother. 47: 1193– 1199.
5. Aperis, G., and, E. Mylonakis. 2006. Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations. Expert Opin. Investig. Drugs 15: 579– 602.
6. Arrese, J. E.,, P. Delvenne,, J. Van Cutsem,, C. Pierard-Franchimont, and, G. E. Pierard. 1994. Experimental aspergillosis in guinea pigs: influence of itraconazole on fungaemia and invasive fungal growth. Mycoses 37: 117– 122.
7. Barone, J. A.,, B. L. Moskovitz,, J. Guarnieri,, A. E. Hassell,, J. L. Co-laizzi,, R. H. Bierman, and, L. Jessen. 1998a. Enhanced bioavailability of itraconazole in hydroxypropyl-fj-cyclodextrin solution versus capsules in healthy volunteers. Antimicrob. Agents Chemother. 42: 1862– 1865.
8. Barone, J. A.,, B. L. Moskovitz,, J. Guarnieri,, A. E. Hassell,, J. L. Co-laizzi,, R. H. Bierman, and, L. Jessen. 1998b. Food interaction and steady-state pharmacokinetics of itraconazole oral solution in healthy volunteers. Pharmacotherapy 18: 295– 301.
9. Bartroli, J.,, E. Turmo,, M. Alguero,, E. Boncompte,, M. L. Vericat,, L. Conte,, J. Ramis,, M. Merlos,, J. Garcia-Rafanell, and, J. Forn. 1998. New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3 H)-quinazolinones. J. Med. Chem. 41: 1869– 1882.
10. Bermudez, M.,, J. L. Fuster,, E. Llinares,, A. Galera, and, C. Gonzalez. 2005. Itraconazole-related increased vincristine neurotoxicity: case report and review of literature. J. Pediatr. Hematol. Oncol. 27: 389– 392.
11. Boelaert, J.,, M. Schurgers,, E. Matthys,, R. Daneels,, A. van Peer,, K. de Beule,, R. Woestenborghs, and, J. Heykants. 1988. Itraconazole pharmacokinetics in patients with renal dysfunction. Antimicrob. Agents Chemother. 32: 1595– 1597.
12. Bohme, A.,, A. Ganser, and, D. Hoelzer. 1995. Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL. Ann. Hematol. 71: 311– 312.
13. Boogaerts, M.,, D. J. Winston,, E. J. Bow,, G. Garber,, A. C. Reboli,, A. P. Schwarer,, N. Novitzky,, A. Boehme,, E. Chwetzoff, and, K. de Beule. 2001. Intravenous and oral itraconazole versus intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. A randomized, controlled trial. Ann. Intern. Med. 135: 412– 422.
14. Cacciapuoti, A.,, D. Loebenberg,, E. Corcoran,, F. Menzel, Jr.,, E. L. Moss, Jr.,, C. Norris,, M. Michalski,, K. Raynor,, J. Halpern,, C. Men-drick,, B. Arnold,, B. Antonacci,, R. Parmegiani,, T. Yarosh-Tomaine,, G. H. Miller, and, R. S. Hare. 2000. In vitro and in vivo activities of SCH 56592 (posaconazole), a new triazole antifungal agent, against Aspergillus and Candida. Antimicrob. Agents Chemother. 44: 2017– 2022.
15. Camuset, J.,, H. Nunes,, M. C. Dombret,, A. Bergeron,, P. Henno,, B. Philippe,, G. Dauriat,, G. Mangiapan,, A. Rabbat, and, J. Cadranel. 2007. Treatment of chronic pulmonary aspergillosis by voriconazole in nonimmunocompromised patients. Chest 131: 1435– 1441.
16. Capilla, J.,, M. Ortoneda,, F. J. Pastor, and, J. Guarro. 2001. In vitro antifungal activities of the new triazole UR-9825 against clinically important filamentous fungi. Antimicrob. Agents Chemother. 45: 2635– 2637.
17. Capilla, J.,, C. Yustes,, E. Mayayo,, B. Fernandez,, M. Ortoneda,, F. J. Pastor, and, J. Guarro. 2003. Efficacy of albaconazole (UR-9825) in treatment of disseminated Scedosporium prolificans infection in rabbits. Antimicrob. Agents Chemother. 47: 1948– 1951.
18. Chan, J. D. 1998. Pharmacokinetic drug interactions of vinca alkaloids: summary of case reports. Pharmacotherapy 18: 1304– 1307.
19. Cornely, O. A.,, J. Maertens,, D. J. Winston,, J. Perfect,, A. J. Ullmann,, T. J. Walsh,, D. Helfgott,, J. Holowiecki,, D. Stockelberg,, Y. T. Goh,, M. Petrini,, C. Hardalo,, R. Suresh, and, D. Angulo-Gonzalez. 2007. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 356: 348– 359.
20. Courtney, R.,, S. Pai,, M. Laughlin,, J. Lim, and, V. Batra. 2003. Phar-macokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob. Agents Chemother. 47: 2788– 2795.
21. Courtney, R.,, D. Wexler,, E. Radwanski,, J. Lim, and, M. Laughlin. 2004. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br. J. Clin. Pharmacol. 57: 218– 222.
22. Cuenca-Estrella, M.,, A. Gomez-Lopez,, E. Mellado,, G. Garcia-Effron,, A. Monzon, and, J. L. Rodriguez-Tudela. 2005. In vitro activity of ravuconazole against 923 clinical isolates of nondermatophyte filamentous fungi. Antimicrob. Agents Chemother. 49: 5136– 5138.
23. Dannaoui, E.,, E. Borel,, F. Persat,, M. F. Monier,, M. A. Piens, et al. 1999. In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. J. Med. Microbiol. 48: 1087– 1093.
24. Dannaoui, E.,, E. Borel,, F. Persat,, M. A. Piens, and, S. Picot. 2000. Amphotericin B resistance of Aspergillus terreus in a murine model of disseminated aspergillosis. J. Med. Microbiol. 49: 601– 606.
25. de Almeida, M. B.,, M. H. Bussamra, and, J. C. Rodrigues. 2006. Allergic bronchopulmonary aspergillosis in paediatric cystic fibrosis patients. Paediatr. Respir. Rev. 7: 67– 72.
26. Denning, D. W. 1996. Therapeutic outcome in invasive aspergillosis. Clin. Infect. Dis. 23: 608– 615.
27. Denning, D. W.,, J. Y. Lee,, J. S. Hostetler,, P. Pappas,, C. A. Kauffman,, D. H. Dewsnup,, J. N. Galgiani,, J. R. Graybill,, A. M. Sugar,, A. Catanzaro, et al. 1994. Multicenter trial of oral itraconazole therapy for invasive aspergillosis. Am. J. Med. 97: 135– 144.
28. Denning, D. W.,, P. Ribaud,, N. Milpied,, D. Caillot,, R. Herbrecht,, E. Thiel,, A. Haas,, M. Ruhnke, and, H. Lode. 2002. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin. Infect. Dis. 34: 563– 571.
29. Denning, D. W.,, K. Riniotis,, R. Dobrashian, and, H. Sambatakou. 2003. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin. Infect. Dis. 37: (Suppl. 3): S265– S280.
30. Denning, D. W.,, J. E. Van Wye,, N. J. Lewiston, and, D. A. Stevens. 1991. Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. Chest 100: 813– 819.
31. De Pauw, B. E., and, J. P. Donnelly. 2007. Prophylaxis and aspergillosis: has the principle been proven? N. Engl. J. Med. 356: 409– 411.
32. Diekema, D. J.,, S. A. Messer,, R. J. Hollis,, R. N. Jones, and, M. A. Pfaller. 2003. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J. Clin. Microbiol. 41: 3623– 3626.
33. Espinel-Ingroff, A. 1998. In vitro activity of the new triazole voricon-azole (UK-109,496) against opportunistic filamentous and dimorphic fungi and common and emerging yeast pathogens. J. Clin. Microbiol. 36: 198– 202.
34. Ezzet, F.,, D. Wexler,, R. Courtney,, G. Krishna,, J. Lim, and, M. Laugh-lin. 2005. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin. Pharmacokinet. 44: 211– 220.
35. Food and Drug Administration. 2001. Advisory for fungal drugs. FDA Consum. 35: 4.
36. Food and Drug Administration. 2003. Sporanox (itraconazole) oral solution label information. http://www.fda.gov/cder/foi/label/2003/20657slr010sporanoxlbl.pdf. Accessed 15 March 2008.
37. Food and Drug Administration. 2004a. Sporanox (itraconazole) capsules label information. http://www.fda.gov/cder/foi/label/2004/20083s034,035lbl.pdf. Accessed 15 March 2008.
38. Food and Drug Administration. 2004b. Sporanox (itraconazole) injection label information. http://www.fda.gov/cder/foi/label/2004/20966s011lbl.pdf. Accessed 15 March 2008.
39. Food and Drug Administration. 2006. Noxafil oral suspension product information. http://www.fda.gov/cder/foi/label/2006/022027lbl.pdf. Accessed 15 March 2008.
40. Food and Drug Administration. 2008. Vfend (voriconazole) iv, tablets and oral supension label information. http://www.fda.gov/cder/foi/label/2008/021266s023,021267s024,021630s013lbl.pdf. Accessed 15 March 2008.
41. Fuhrmann, V.,, P. Schenk,, W. Jaeger,, M. Miksits,, N. Kneidinger,, J. Warszawska,, U. Holzinger,, R. Kitzberger, and, F. Thalhammer. 2007. Pharmacokinetics of voriconazole during continuous veno-venous haemodiafiltration. J. Antimicrob. Chemother. 60: 1085– 1090.
42. Gallin, J. I.,, D. W. Alling,, H. L. Malech,, R. Wesley,, D. Koziol,, B. Marciano,, E. M. Eisenstein,, M. L. Turner,, E. S. DeCarlo,, J. M. Starling, and, S. M. Holland. 2003. Itraconazole to prevent fungal infections in chronic granulomatous disease. N. Engl. J. Med. 348: 2416– 2422.
43. Glasmacher, A.,, O. Cornely,, A. J. Ullmann,, U. Wedding,, H. Bodenstein,, H. Wandt,, C. Boewer,, R. Pasold,, H. H. Wolf,, M. Hanel,, G. Dolken,, C. Junghanss,, R. Andreesen, and, H. Bertz. 2006. An open-label randomized trial comparing itraconazole oral solution with flu-conazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutro-penia. J. Antimicrob. Chemother. 57: 317– 325.
44. Glasmacher, A.,, C. Hahn,, C. Leutner,, E. Molitor,, E. Wardelmann,, C. Losem,, T. Sauerbruch,, G. Marklein, and, I. G. Schmidt-Wolf. 1999. Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole. Mycoses 42: 443– 451.
45. Glasmacher, A., and, A. Prentice. 2006. Current experience with itra-conazole in neutropenic patients: a concise overview of pharmacological properties and use in prophylactic and empirical antifungal therapy. Clin. Microbiol. Infect. 12: (Suppl. 7): 84– 90.
46. Glasmacher, A.,, A. Prentice,, M. Gorschluter,, S. Engelhart,, C. Hahn,, B. Djulbegovic, and, I. G. Schmidt-Wolf. 2003. Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J. Clin. Oncol. 21: 4615– 4626.
47. Goodwin, M. L., and, R. H. Drew. 2008. Antifungal serum concentration monitoring: an update. J. Antimicrob. Chemother. 61: 17– 25.
48. Graybill, J. R.,, L. K. Najvar,, G. M. Gonzalez,, S. Hernandez, and, R. Bocanegra. 2003. Improving the mouse model for studying the efficacy of voriconazole. J. Antimicrob. Chemother. 51: 1373– 1376.
49. Greenberg, R. N.,, K. Mullane,, J. A. van Burik,, I. Raad,, M. J. Abzug,, G. Anstead,, R. Herbrecht,, A. Langston,, K. A. Marr,, G. Schiller,, M. Schuster,, J. R. Wingard,, C. E. Gonzalez,, S. G. Revankar,, G. Corcoran,, R. J. Kryscio, and, R. Hare. 2006. Posaconazole as salvage therapy for zygomycosis. Antimicrob. Agents Chemother. 50: 126– 133.
50. Groll, A. H.,, D. Mickiene,, V. Petraitis,, R. Petraitiene,, A. Kelaher,, A. Sarafandi,, G. Wuerthwein,, J. Bacher, and, T. J. Walsh. 2005. Com-partmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its dilysine phosphoester prodrug (BMS-379224) in rabbits. J. Anti-microb. Chemother. 56: 899– 907.
51. Guinea, J.,, T. Pelaez,, L. Alcala,, M. J. Ruiz-Serrano, and, E. Bouza. 2005. Antifungal susceptibility of 596 Aspergillus fumigatus strains isolated from outdoor air, hospital air, and clinical samples: analysis by site of isolation. Antimicrob. Agents Chemother. 49: 3495– 3497.
52. Guinea, J.,, T. Pelaez,, S. Recio,, M. Torres-Narbona, and, E. Bouza. 2008. In vitro antifungal activities of isavuconazole (BAL4815), vor-iconazole, and fluconazole against 1,007 isolates of zygomycete, Candida, Aspergillus, Fusarium, and Scedosporium species. Antimicrob. Agents Chemother. 52: 1396– 1400.
53. Gupta, A. K.,, C. Leonardi,, R. R. Stoltz,, P. F. Pierce, and, B. Conetta. 2005. 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. 19: 437– 443.
54. Hata, K.,, J. Kimura,, H. Miki,, T. Toyosawa,, M. Moriyama, and, K. Katsu. 1996a. Efficacy of ER-30346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryp-tococcosis. Antimicrob. Agents Chemother. 40: 2243– 2247.
55. Hata, K.,, J. Kimura,, H. Miki,, T. Toyosawa,, T. Nakamura, and, K. Katsu. 1996b. In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum. Antimicrob. Agents Chemother. 40: 2237– 2242.
56. Herbrecht, R. 2004a. Posaconazole: a potent, extended-spectrum tri-azole anti-fungal for the treatment of serious fungal infections. Int. J. Clin. Pract. 58: 612– 624.
57. Herbrecht, R. 2004b. Voriconazole: therapeutic review of a new azole antifungal. Expert Rev. Anti Infect. Ther. 2: 485– 497.
58. Herbrecht, R.,, D. W. Denning,, T. F. Patterson,, J. E. Bennett,, R. E. Greene,, J. W. Oestmann,, W. V. Kern,, K. A. Marr,, P. Ribaud,, O. Lortholary,, R. Sylvester,, R. H. Rubin,, J. R. Wingard,, P. Stark,, C. Durand,, D. Caillot,, E. Thiel,, P. H. Chandrasekar,, M. R. Hodges,, H. T. Schlamm,, P. F. Troke, and, B. de Pauw. 2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347: 408– 415.
59. Herbrecht, R.,, U. Fluckiger,, B. Gachot,, P. Ribaud,, A. Thiebaut, and, C. Cordonnier. 2007. Treatment of invasive Candida and invasive Aspergillus infections in adult haematological patients. Eur. J.Cancer Suppl. 5: 49– 52.
60. Heykants, J.,, A. van Peer,, V. Van de Velde,, P. Van Rooy,, W. Meuld-ermans,, K. Lavrijsen,, R. Woestenborghs,, J. Van Cutsem, and, G. Cauwenbergh. 1989. The clinical pharmacokinetics of itraconazole: an overview. Mycoses 32: (Suppl. 1): 67– 87.
61. Husain, S.,, D. L. Paterson,, S. Studer,, J. Pilewski,, M. Crespo,, D. Zal-donis,, K. Shutt,, D. L. Pakstis,, A. Zeevi,, B. Johnson,, E. J. Kwak, and, K. R. McCurry. 2006. Voriconazole prophylaxis in lung transplant recipients. Am. J. Transplant. 6: 3008– 3016.
62. Imai, J. K.,, G. Singh,, K. V. Clemons, and, D. A. Stevens. 2004. Efficacy of posaconazole in a murine model of central nervous system aspergillosis. Antimicrob. Agents Chemother. 48: 4063– 4066.
63. Imhof, A.,, S. A. Balajee,, D. N. Fredricks,, J. A. Englund, and, K. A. Marr. 2004. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin. Infect. Dis. 39: 743– 746.
64. Jain, L. R., and, D. W. Denning. 2006. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J. Infect. 52: e133– e137.
65. Johnson, L. B., and, C. A. Kauffman. 2003. Voriconazole: a new tri-azole antifungal agent. Clin. Infect. Dis. 36: 630– 637.
66. Kirkpatrick, W. R.,, R. K. McAtee,, A. W. Fothergill,, D. Loebenberg,, M. G. Rinaldi, and, T. F. Patterson. 2000a. Efficacy of SCH56592 in a rabbit model of invasive aspergillosis. Antimicrob. Agents Che-mother. 44: 780– 782.
67. Kirkpatrick, W. R.,, R. K. McAtee,, A. W. Fothergill,, M. G. Rinaldi, and, T. F. Patterson. 2000b. Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis. Antimicrob. Agents Chemother. 44: 2865– 2868.
68. Kirkpatrick, W. R.,, S. Perea,, B. J. Coco, and, T. F. Patterson. 2002. Efficacy of ravuconazole (BMS-207147) in a guinea pig model of disseminated aspergillosis. J. Antimicrob. Chemother. 49: 353– 357.
69. Kontoyiannis, D. P.,, M. S. Lionakis,, R. E. Lewis,, G. Chamilos,, M. Healy,, C. Perego,, A. Safdar,, H. Kantarjian,, R. Champlin,, T. J. Walsh, and, I. I. Raad. 2005. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J. Infect. Dis. 191: 1350– 1360.
70. Krcmery, V., Jr.,, E. Oravcova,, S. Spanik,, M. Mrazova-Studena,, J. Trupl,, A. Kunova,, K. Stopkova-Grey,, E. Kukuckova,, I. Krupova,, A. Demitrovicova, and, K. Kralovicova. 1998. Nosocomial breakthrough fungaemia during antifungal prophylaxis or empirical antifungal therapy in 41 cancer patients receiving antineoplastic chemotherapy: analysis of aetiology risk factors and outcome. J. Antimicrob. Chemother. 41: 373– 380.
71. Krieter, P.,, B. Flannery,, T. Musick,, M. Gohdes,, M. Martinho, and, R. Courtney. 2004. Disposition of posaconazole following single-dose oral administration in healthy subjects. Antimicrob. Agents Chemother. 48: 3543– 3551.
72. Leveque, D.,, Y. Nivoix,, F. Jehl, and, R. Herbrecht. 2006. Clinical pharmacokinetics of voriconazole. Int. J. Antimicrob. Agents 27: 274– 284.
73. Levin, M. D.,, J. G. den Hollander,, B. van der Holt,, B. J. Rijnders,, M. van Vliet,, P. Sonneveld, and, R. H. van Schaik. 2007. Hepato-toxicity of oral and intravenous voriconazole in relation to cyto-chrome P450 polymorphisms. J. Antimicrob. Chemother. 60: 1104– 1107.
74. Maertens, J., and, M. Boogaerts. 2005. The place for itraconazole in treatment. J. Antimicrob. Chemother. 56: (Suppl. 1): i33– i38.
75. Maertens, J. A.,, P. Fr’ere,, C. Lass-Floerl,, W. Heinz, and, O. A. Cornely. 2007. Primary antifungal prophylaxis in leukemia patients. Eur. J. Cancer Suppl. 5: 43– 48.
76. Manavathu, E. K.,, J. L. Cutright,, D. Loebenberg, and, P. H. Chan-drasekar. 2000. A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole, voriconazole and posaconazole (SCH 56592). J. Antimicrob. Chemother. 46: 229– 234.
77. Mantadakis, E.,, G. Amoiridis,, A. Kondi, and, M. Kalmanti. 2007. Possible increase of the neurotoxicity of vincristine by the concurrent use of posaconazole in a young adult with leukemia. J. Pediatr. Hematol. Oncol. 29: 130.
78. Marchetti, O.,, C. Cordonnier, and, T. Calandra. 2007. Empirical antifungal therapy in neutropenic cancer patients with persistent fever. Eur. J. Cancer Suppl. 5: 32– 42.
79. Marr, K. A.,, F. Crippa,, W. Leisenring,, M. Hoyle,, M. Boeckh,, S. A. Balajee,, W. G. Nichols,, B. Musher, and, L. Corey. 2004a. Itracon- azole versus fluconazole for prevention of fungal infections in patients receiving allogeneic stem cell transplants. Blood 103: 1527– 1533.
80. Marr, K. A.,, W. Leisenring,, F. Crippa,, J. T. Slattery,, L. Corey,, M. Boeckh, and, G. B. McDonald. 2004b. Cyclophosphamide metabolism is affected by azole antifungals. Blood 103: 1557– 1559.
81. Martin, M. V.,, J. Yates, and, C. A. Hitchcock. 1997. Comparison of voriconazole (UK-109,496) and itraconazole in prevention and treatment of Aspergillus fumigatus endocarditis in guinea pigs. Antimicrob. Agents Chemother. 41: 13– 16.
82. Marty, F. M.,, L. A. Cosimi, and, L. R. Baden. 2004. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N. Engl. J. Med. 350: 950– 952.
83. Messer, S. A.,, R. N. Jones, and, T. R. Fritsche. 2006. International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003). J. Clin. Microbiol. 44: 1782– 1787.
84. Mikamo, H.,, X. H. Yin,, Y. Hayasaki,, Y. Shimamura,, K. Uesugi,, N. Fukayama,, M. Satoh, and, T. Tamaya. 2002. Penetration of ravu-conazole, a new triazole antifungal, into rat tissues. Chemotherapy 48: 7– 9.
85. Miller, J. L.,, W. A. Schell,, E. A. Wills,, D. L. Toffaletti,, M. Boyce,, D. K. Benjamin, Jr.,, J. Bartroli, and, J. R. Perfect. 2004. In vitro and in vivo efficacies of the new triazole albaconazole against Cryp-tococcus neoformans. Antimicrob. Agents Chemother. 48: 384– 387.
86. Minassian, B.,, E. Huczko,, T. Washo,, D. Bonner, and, J. Fung-Tomc. 2003. In vitro activity of ravuconazole against Zygomycetes, Sce-dosporium and Fusarium isolates. Clin. Microbiol. Infect. 9: 1250– 1252.
87. Miyama, T.,, H. Takanaga,, H. Matsuo,, K. Yamano,, K. Yamamoto,, T. Iga,, M. Naito,, T. Tsuruo,, H. Ishizuka,, Y. Kawahara, and, Y. Sawada. 1998. P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier. Antimicrob. Agents Chemother. 42: 1738– 1744.
88. Mouas, H.,, I. Lutsar,, B. Dupont,, O. Fain,, R. Herbrecht,, F. X. Les-cure, and, O. Lortholary. 2005. Voriconazole for invasive bone aspergillosis: a worldwide experience of 20 cases. Clin. Infect. Dis. 40: 1141– 1147.
89. Najvar, L. K.,, A. Cacciapuoti,, S. Hernandez,, J. Halpern,, R. Bocane-gra,, M. Gurnani,, F. Menzel,, D. Loebenberg, and, J. R. Graybill. 2004. Activity of posaconazole combined with amphotericin B against Aspergillus flavus infection in mice: comparative studies in two laboratories. Antimicrob. Agents Chemother. 48: 758– 764.
90. Oakley, K. L.,, G. Morrissey, and, D. W. Denning. 1997. Efficacy of SCH-56592 in a temporarily neutropenic murine model of invasive aspergillosis with an itraconazole-susceptible and an itraconazole-resistant isolate of Aspergillus fumigatus. Antimicrob. Agents Chemother. 41: 1504– 1507.
91. Pagano, L.,, B. Gleissner, and, L. Fianchi. 2005. Breakthrough zygo-mycosis and voriconazole. J. Infect. Dis. 192: 1496– 1497.
92. Panagopoulou, P.,, J. Filioti,, E. Farmaki,, A. Maloukou, and, E. Roilides. 2007. Filamentous fungi in a tertiary care hospital: environmental surveillance and susceptibility to antifungal drugs. Infect. Control Hosp. Epidemiol. 28: 60– 67.
93. Pascual, A.,, T. Calandra,, S. Bolay,, T. Buclin,, J. Bille, and, O. Mar-chetti. 2008. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin. Infect. Dis. 46: 201– 211.
94. Pascual, A.,, V. Nieth,, T. Calandra,, J. Bille,, S. Bolay,, L. A. Decosterd,, T. Buclin,, P. A. Majcherczyk,, D. Sanglard, and, O. Marchetti. 2007. Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods. Anti-microb. Agents Chemother. 51: 137– 143.
95. Pasqualotto, A. C., and, D. W. Denning. 2008. New and emerging treatments for fungal infections. J. Antimicrob. Chemother. 61: (Suppl. 1): i19– i30.
96. Pasqualotto, A. C.,, M. Shah,, R. Wynn, and, D. W. Denning. 2008. Voriconazole plasma monitoring. Arch. Dis. Child. 93: 578– 581.
97. Patterson, T. F.,, A. W. Fothergill, and, M. G. Rinaldi. 1993. Efficacy of itraconazole solution in a rabbit model of invasive aspergillosis. Antimicrob. Agents Chemother. 37: 2307– 2310.
98. Pavie, J.,, C. Lacroix,, D. G. Hermoso,, M. Robin,, C. Ferry,, A. Bergeron,, M. Feuilhade,, F. Dromer,, E. Gluckman,, J. M. Molina, and, P. Ribaud. 2005. Breakthrough disseminated Aspergillus ustus infection in allogeneic hematopoietic stem cell transplant recipients receiving voriconazole or caspofungin prophylaxis. J. Clin. Microbiol. 43: 4902– 4904.
99. Peng, L. W., and, Y. H. Lien. 2005. Pharmacokinetics of single, oral-dose voriconazole in peritoneal dialysis patients. Am. J. Kidney Dis. 45: 162– 166.
100. Petraitiene, R.,, V. Petraitis,, A. H. Groll,, T. Sein,, S. Piscitelli,, M. Can-delario,, A. Field-Ridley,, N. Avila,, J. Bacher, and, T. J. Walsh. 2001. Antifungal activity and pharmacokinetics of posaconazole (SCH 56592) in treatment and prevention of experimental invasive pulmonary aspergillosis: correlation with galactomannan antigenemia. Antimicrob. Agents Chemother. 45: 857– 869.
101. Petraitiene, R.,, V. Petraitis,, C. A. Lyman,, A. H. Groll,, D. Mickiene,, J. Peter,, J. Bacher,, K. Roussillon,, M. Hemmings,, D. Armstrong,, N. A. Avila, and, T. J. Walsh. 2004. 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. 48: 1188– 1196.
102. Pfaller, M. A.,, S. A. Messer,, R. J. Hollis, and, R. N. Jones. 2002. 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. 46: 1032– 1037.
103. Ramos, G.,, M. Cuenca-Estrella,, A. Monzon, and, J. L. Rodriguez-Tudela. 1999. In-vitro comparative activity of UR-9825, itraconazole and fluconazole against clinical isolates of Candida spp. J. Antimicrob. Chemother. 44: 283– 286.
104. Robatel, C.,, M. Rusca,, C. Padoin,, O. Marchetti,, L. Liaudet, and, T. Buclin. 2004. Disposition of voriconazole during continuous veno-venous haemodiafiltration (CVVHDF) in a single patient. J. Anti-microb. Chemother. 54: 269– 270.
105. Roffey, S. J.,, S. Cole,, P. Comby,, D. Gibson,, S. G. Jezequel,, A. N. Nedderman,, D. A. Smith,, D. K. Walker, and, N. Wood. 2003. The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human. Drug Metab. Dispos. 31: 731– 741.
106. Sambatakou, H.,, B. Dupont,, H. Lode, and, D. W. Denning. 2006. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am. J. Med. 119: 527– 524.
107. Schmitt, H. J.,, F. Edwards,, J. Andrade,, Y. Niki, and, D. Armstrong. 1992. Comparison of azoles against aspergilli in vitro and in an experimental model of pulmonary aspergillosis. Chemotherapy 38: 118– 126.
108. Schwartz, S.,, M. Ruhnke,, P. Ribaud,, L. Corey,, T. Driscoll,, O. A. Cornely,, U. Schuler,, I. Lutsar,, P. Troke, and, E. Thiel. 2005. Improved outcome in central nervous system aspergillosis, using vor-iconazole treatment. Blood 106: 2641– 2645.
109. Sharkey, P. K.,, M. G. Rinaldi,, J. F. Dunn,, T. C. Hardin,, R. J. Fetchick, and, J. R. Graybill. 1991. High-dose itraconazole in the treatment of severe mycoses. Antimicrob. Agents Chemother. 35: 707– 713.
110. Singh, R., and, T. Cundy. 2005. Itraconazole-induced painful neuropathy in a man with type 1 diabetes. Diabetes Care 28: 225.
111. Sugar, A. M., and, X. P. Liu. 2000. Effect of grapefruit juice on serum voriconazole concentrations in the mouse. Med. Mycol. 38: 209– 212.
112. Sugar, A. M., and, X. P. Liu. 2001. Efficacy of voriconazole in treatment of murine pulmonary blastomycosis. Antimicrob. Agents Che-mother. 45: 601– 604.
113. Trifilio, S.,, G. Pennick,, J. Pi,, J. Zook,, M. Golf,, K. Kaniecki,, S. Singhal,, S. Williams,, J. Winter,, M. Tallman,, L. Gordon,, O. Frankfurt,, A. Evens, and, J. Mehta. 2007a. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer 109: 1532– 1535.
114. Trifilio, S.,, S. Singhal,, S. Williams,, O. Frankfurt,, L. Gordon,, A. Evens,, J. Winter,, M. Tallman,, J. Pi, and, J. Mehta. 2007b. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant. 40: 451– 456.
115. Trifilio, S. M.,, C. L. Bennett,, P. R. Yarnold,, J. M. McKoy,, J. Parada,, J. Mehta,, G. Chamilos,, F. Palella,, L. Kennedy,, K. Mullane,, M. S. Tallman,, A. Evens,, M. H. Scheetz,, W. Blum, and, D. P. Kontoyian-nis. 2007c. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 39: 425– 429.
116. Tsiodras, S.,, R. Zafiropoulou,, E. Kanta,, C. Demponeras,, N. Karan-dreas, and, E. K. Manesis. 2005. Painful peripheral neuropathy associated with voriconazole use. Arch. Neurol. 62: 144– 146.
117. Ullmann, A. J.,, J. H. Lipton,, D. H. Vesole,, P. Chandrasekar,, A. Lang-ston,, S. R. Tarantolo,, H. Greinix,, D. A. Morais,, V. Reddy,, N. Boparai,, L. Pedicone,, H. Patino, and, S. Durrant. 2007. Posacona-zole or fluconazole for prophylaxis in severe graft-versus-host disease. N. Engl. J. Med. 356: 335– 347.
118. van Burik, J. A.,, R. S. Hare,, H. F. Solomon,, M. L. Corrado, and, D. P. Kontoyiannis. 2006. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin. Infect. Dis. 42: e61– e65.
119. Van de Velde, V. J.,, A. P. Van Peer,, J. J. Heykants,, R. J. Woesten-borghs,, P. Van Rooy,, K. L. De Beule, and, G. F. Cauwenbergh. 1996. Effect of food on the pharmacokinetics of a new hydroxypropyl-beta-cyclodextrin formulation of itraconazole. Phar-macotherapy 16: 424– 428.
120. van’t Hek, L. G.,, P. E. Verweij,, C. M. Weemaes,, R. van Dalen,, J. B. Yntema, and, J. F. Meis. 1998. Successful treatment with voricon-azole of invasive aspergillosis in chronic granulomatous disease. Am. J. Respir. Crit. Care Med. 157: 1694– 1696.
121. van’t Wout, J. W.,, I. Novakova,, C. A. Verhagen,, W. E. Fibbe,, B. E. De Pauw, and, J. W. van der Meer. 1991. The efficacy of itraconazole against systemic fungal infections in neutropenic patients: a randomised comparative study with amphotericin B. J. Infect. 22: 45– 52.
122. Verweij, P. E.,, D. T. te Dorsthorst,, A. J. Rijs,, H. G. Vries-Hospers, and, J. F. Meis. 2002. Nationwide survey of in vitro activities of itraconazole and voriconazole against clinical Aspergillus fumigatus isolates cultured between 1945 and 1998. J. Clin. Microbiol. 40: 2648– 2650.
123. von Mach, M. A.,, J. Burhenne, and, L. S. Weilemann. 2006. Accumulation of the solvent vehicle sulphobutylether beta cyclodextrin sodium in critically ill patients treated with intravenous voriconazole under renal replacement therapy. BMC Clin. Pharmacol. 6: 6.
124. Walsh, T. J.,, E. J. Anaissie,, D. W. Denning,, R. Herbrecht,, D. P. Kon-toyiannis,, K. A. Marr,, V. A. Morrison,, B. H. Segal,, W. J. Steinbach,, D. A. Stevens,, J. A. van Burik,, J. R. Wingard, and, T. F. Patterson. 2008. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 46: 327– 360.
125. Walsh, T. J.,, M. O. Karlsson,, T. Driscoll,, A. G. Arguedas,, P. Ad-amson,, X. Saez-Llorens,, A. J. Vora,, A. C. Arrieta,, J. Blumer,, I. Lutsar,, P. Milligan, and, N. Wood. 2004. Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob. Agents Chemother. 48: 2166– 2172.
126. Walsh, T. J.,, I. Lutsar,, T. Driscoll,, B. Dupont,, M. Roden,, P. Ghah-ramani,, M. Hodges,, A. H. Groll, and, J. R. Perfect. 2002a. Vori- conazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr. Infect. Dis. J. 21: 240– 248.
127. Walsh, T. J.,, P. Pappas,, D. J. Winston,, H. M. Lazarus,, F. Petersen,, J. Raffalli,, S. Yanovich,, P. Stiff,, R. Greenberg,, G. Donowitz,, M. Schuster,, A. Reboli,, J. Wingard,, C. Arndt,, J. Reinhardt,, S. Hadley,, R. Finberg,, M. Laverdiere,, J. Perfect,, G. Garber,, G. Fioritoni,, E. Anaissie, and, J. Lee. 2002b. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N. Engl. J. Med. 346: 225– 234.
128. Walsh, T. J.,, V. Petraitis,, R. Petraitiene,, A. Field-Ridley,, D. Sutton,, M. Ghannoum,, T. Sein,, R. Schaufele,, J. Peter,, J. Bacher,, H. Casler,, D. Armstrong,, A. Espinel-Ingroff,, M. G. Rinaldi, and, C. A. Lyman. 2003. Experimental pulmonary aspergillosis due to Aspergillus ter-reus: pathogenesis and treatment of an emerging fungal pathogen resistant to amphotericin B. J. Infect. Dis. 188: 305– 319.
129. Walsh, T. J.,, I. Raad,, T. F. Patterson,, P. Chandrasekar,, G. R. Don-owitz,, R. Graybill,, R. E. Greene,, R. Hachem,, S. Hadley,, R. Her-brecht,, A. Langston,, A. Louie,, P. Ribaud,, B. H. Segal,, D. A. Stevens,, J. A. van Burik,, C. S. White,, G. Corcoran,, J. Gogate,, G. Krishna,, L. Pedicone,, C. Hardalo, and, J. R. Perfect. 2007. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin. Infect. Dis. 44: 2– 12.
130. Wark, P. A.,, P. G. Gibson, and, A. J. Wilson. 2004. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst. Rev. 3: CD001108.
131. Warn, P. A.,, A. Sharp, and, D. W. Denning. 2006a. In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp. J. Antimicrob. Chemother. 57: 135– 138.
132. Warn, P. A.,, A. Sharp,, J. Mosquera,, J. Spickermann,, A. Schmitt-Hoffmann,, M. Heep, and, D. W. Denning. 2006b. Comparative in vivo activity of BAL4815, the active component of the prodrug BAL8557, in a neutropenic murine model of disseminated Aspergil-lus flavus. J. Antimicrob. Chemother. 58: 1198– 1207.
133. Weiler, S.,, H. Zoller,, I. Graziadei,, W. Vogel,, R. Bellmann-Weiler,, M. Joannidis, and, R. Bellmann. 2007. Altered pharmacokinetics of voriconazole in a patient with liver cirrhosis. Antimicrob. Agents Che-mother. 51: 3459– 3460.
134. Wheat, J.,, R. Hafner,, M. Wulfsohn,, P. Spencer,, K. Squires,, W. Pow-derly,, B. Wong,, M. Rinaldi,, M. Saag,, R. Hamill,, R. Murphy,, P. Connolly-Stringfield,, N. Briggs, and, S. Owens. 1993. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann. Intern. Med. 118: 610– 616.
135. Willems, L.,, R. van der Geest, and, K. de Beule. 2001. Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamics. J. Clin. Pharm. Ther. 26: 159– 169.
136. Winston, D. J., and, R. W. Busuttil. 2002. Randomized controlled trial of oral itraconazole solution versus intravenous/oral fluconazole for prevention of fungal infections in liver transplant recipients. Transplantation 74: 688– 695.
137. Winston, D. J.,, R. T. Maziarz,, P. H. Chandrasekar,, H. M. Lazarus,, M. Goldman,, J. L. Blumer,, G. J. Leitz, and, M. C. Territo. 2003. Intravenous and oral itraconazole versus intravenous and oral flu-conazole for long-term antifungal prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. A multicenter, randomized trial. Ann. Intern. Med. 138: 705– 713.

Tables

Azoles
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Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
/content/10.1128/9781555815523.ch31.ch31tab01
Table 1.
Availability of anti- azoles and their approved indications
Generic image for table
Table 1.

Availability of anti- azoles and their approved indications

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
/content/10.1128/9781555815523.ch31.ch31tab02
Table 2.
In vitro activities of azoles and amphotericin B against spp. from clinical or environmental sources
Generic image for table
Table 2.

In vitro activities of azoles and amphotericin B against spp. from clinical or environmental sources

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31
/content/10.1128/9781555815523.ch31.ch31tab03
Table 3.
Main pharmacokinetics characteristics and recommended dosages for itraconazole, voriconazole, and posaconazole
Generic image for table
Table 3.

Main pharmacokinetics characteristics and recommended dosages for itraconazole, voriconazole, and posaconazole

Citation: Herbrecht R, Nivoix Y. 2009. Azoles, p 417-434. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch31

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