Mycopathologia

, Volume 168, Issue 6, pp 313–327

Antifungal Therapy for Invasive Fungal Diseases in Allogeneic Stem Cell Transplant Recipients: An Update

  • Dustin T. Wilson
  • Richard H. Drew
  • John R. Perfect
Article

Abstract

Invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in allogeneic stem cell transplant (SCT) recipients. While the most common pathogens are Candida spp. and Aspergillus spp., the incidence of infections caused by non-albicans Candida species as well as molds such as Zygomycetes has increased. For many years, amphotericin B deoxycholate (AMB-D) was the only available antifungal for the treatment of IFDs. Within the past decade, there has been a surge of new antifungal agents developed and added to the therapeutic armamentarium. Lipid-based formulations of amphotericin B provide an effective and less nephrotoxic alternative to AMB-D. Voriconazole has now replaced AMB-D as first choice for primary therapy of invasive aspergillosis (IA). Another extended-spectrum triazole, posaconazole, also appears to be a promising agent in the management of zygomycosis, refractory aspergillosis, and for prophylaxis. Members of the newest antifungal class, the echinocandins, are attractive agents in select infections due to their safety profile, and are a more attractive option compared to AMB-D as initial treatment for invasive candidiasis and (based on one study) challenge fluconazole for superiority in management with this mycoses. However, challenges do exist among these newer agents in very high-risk individuals like allogeneic SCT recipients, which may include adverse drug events, drug–drug interactions, variability in oral absorption, and availability of alternative formulations. The addition of newer agents has also stimulated interest in the potential application of combination therapy in serious, life-threatening infections. However, adequate studies are not available for most IFDs; thus, the clinical use of combination therapy is not evidenced based on most cases and preciseness in its use is uncertain. Finally, therapeutic drug monitoring of select antifungals (notably posaconazole and voriconazole) may play an increasing role due to significant interpatient variability in serum concentrations after standard doses.

Keywords

Invasive fungal diseases Antifungals Allogeneic stem cell transplant Amphotericin B Triazoles Echinocandins 

References

  1. 1.
    Marr KA, Carter RA, Crippa F, et al. Epidemiology and outcome of mould infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002;34:909–17. doi:10.1086/339202.PubMedGoogle Scholar
  2. 2.
    Wingard JR. Fungal infections after bone marrow transplant. Biol Blood Marrow Transplant. 1999;5:55–68. doi:10.1053/bbmt.1999.v5.pm10371357.PubMedGoogle Scholar
  3. 3.
    Neuburger S, Maschmeyer G. Update on management of infections in cancer and stem cell transplant patients. Ann Hematol. 2006;85:345–56. doi:10.1007/s00277-005-0048-2.PubMedGoogle Scholar
  4. 4.
    Pfaller MA, Pappas PG, Wingard JR. Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis. 2006;43:S3–14. doi:10.1086/504490.Google Scholar
  5. 5.
    Marr KA, Seidel K, White TC, Bowden RA. Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole. J Infect Dis. 2000;181:309–16. doi:10.1086/315193.PubMedGoogle Scholar
  6. 6.
    Pfaller MA, Diekema DJ, Gibbs DL, et al. Results from the ATREMIS DISK global antifungal surveillance study, 1997 to 2005: an 8.5-year analysis of susceptibilities of Candida species and other yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J Clin Microbiol. 2007;45(6):1735–45. doi:10.1128/JCM.00409-07.PubMedGoogle Scholar
  7. 7.
    Hachem R, Hanna H, Kontoyiannis D, et al. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer. 2008;112(11):2493–9. doi:10.1002/cncr.23466.PubMedGoogle Scholar
  8. 8.
    Morgan J, Wannemuehler KA, Marr KA, et al. Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol. 2005;43(Supp1):S49–58. doi:10.1080/13693780400020113.PubMedGoogle Scholar
  9. 9.
    Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32:358–66. doi:10.1086/318483.PubMedGoogle Scholar
  10. 10.
    Neofytos D, Horn D, Anaissie E, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis 2009;48:265–73. doi:10.1086/595846.PubMedGoogle Scholar
  11. 11.
    Kontoyiannis DP, Lionakis MS, Lewis RE, et al. 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. 2005;191:1350–60. doi:10.1086/428780.PubMedGoogle Scholar
  12. 12.
    Roden MM, Zaoutis TE, Buchanan WL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41:634–53. doi:10.1086/432579.PubMedGoogle Scholar
  13. 13.
    Petrikkos G, Skiada A. Recent advances in antifungal chemotherapy. Int J Antimicrob Agents. 2007;30:108–17. doi:10.1016/j.ijantimicag.2007.03.009.PubMedGoogle Scholar
  14. 14.
    Sable CA, Strohmaier KM, Chodakewitz JA. Advances in antifungal therapy. Annu Rev Med. 2008;59:361–79. doi:10.1146/annurev.med.59.062906.071602.PubMedGoogle Scholar
  15. 15.
    Mohr J, Johnson M, Cooper T, et al. Current options in antifungal pharmacotherapy. Pharmacotherapy. 2008;28(5):614–45. doi:10.1592/phco.28.5.614.PubMedGoogle Scholar
  16. 16.
    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. doi:10.1086/377210.PubMedGoogle Scholar
  17. 17.
    Young LY, Hull CM, Heitman J. Disruption of ergosterol biosynthesis confers resistance to amphotericin B in Candida lusitaniae. Antimicrob Agents Chemother. 2003;47(9):2717–24. doi:10.1128/AAC.47.9.2717-2724.2003.PubMedGoogle Scholar
  18. 18.
    Goodwin SD, Cleary JD, Walawander CA, et al. Pretreatment regimens for adverse events related to infusion of amphotericin B. Clin Infect Dis. 1995;20:755–61.PubMedGoogle Scholar
  19. 19.
    Ostrosky-Zeichner L, Marr KA, Rex JH, Cohen SH. Amphotericin B: time for a new “gold standard”. Clin Infect Dis. 2003;37:415–25. doi:10.1086/376634.PubMedGoogle Scholar
  20. 20.
    Imhof A, Walter R, Schaffner A. Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study. Clin Infect Dis. 2003;36:943–51. doi:10.1086/368312.PubMedGoogle Scholar
  21. 21.
    Peleg AY, Woods ML. Continuous and 4 h infusion of amphotericin B: a comparative study involving high-risk haematology patients. J Antimicrob Chemother. 2004;54(4):803–8. doi:10.1093/jac/dkh403.PubMedGoogle Scholar
  22. 22.
    Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomized controlled trial. BMJ. 2001;322:579–82. doi:10.1136/bmj.322.7286.579.PubMedGoogle Scholar
  23. 23.
    Lewis RE, Wiederhold NP. The solubility ceiling: a rationale for continuous infusion amphotericin B therapy. Clin Infect Dis. 2003;37:871–2. doi:10.1086/377279.PubMedGoogle Scholar
  24. 24.
    Gibbs WJ, Drew RH, Perfect JR. Liposomal amphotericin B: clinical experience and perspectives. Expert Rev Anti Infect Ther. 2005;3(2):167–81. doi:10.1586/14787210.3.2.167.PubMedGoogle Scholar
  25. 25.
    Prentice HG, Hann IM, Herbrecht R, et al. A randomized comparison of liposomal versus conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haematol. 1997;98:711–8. doi:10.1046/j.1365-2141.1997.2473063.x.PubMedGoogle Scholar
  26. 26.
    White MH, Bowden RA, Sandler ES, et al. Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis. 1998;27:296–302. doi:10.1086/514672.PubMedGoogle Scholar
  27. 27.
    Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med. 1999;340:764–71. doi:10.1056/NEJM199903113401004.PubMedGoogle Scholar
  28. 28.
    Alexander BD, Wingard JR. Study of renal safety in amphotericin B lipid complex-treated patients. Clin Infect Dis. 2005;40:S414–21. doi:10.1086/429335.PubMedGoogle Scholar
  29. 29.
    Bowden R, Chandrasekar P, White MH, et al. A double-blind, randomized, controlled trial of amphotericin B colloidal dispersion versus amphotericin B for treatment of invasive aspergillosis in immunocompromised patients. Clin Infect Dis. 2002;35:359–66. doi:10.1086/341401.PubMedGoogle Scholar
  30. 30.
    Johansen HK, Gøtzsche PC. Amphotericin B lipid soluble formulations versus amphotericin B in cancer patients with neutropenia. Cochrane Database Syst Rev 2000; Issue 3. Art. No.: CD000969. doi:10.1002/14651858.CD000969.
  31. 31.
    Groll AH, Lyman CA, Petraitis V, et al. Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations. Antimicrob Agents Chemother. 2006;50(10):3418–23. doi:10.1128/AAC.00241-06.PubMedGoogle Scholar
  32. 32.
    Lewis RE, Liao G, Hou J, et al. Comparative analysis of amphotericin B lipid complex and liposomal amphotericin B kinetics of lung accumulation and fungal clearance in a murine model of acute invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2007;51(4):1253–8. doi:10.1128/AAC.01449-06.PubMedGoogle Scholar
  33. 33.
    Wingard JR, White MH, Anaissie E, et al. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis. 2000;31:1155–63. doi:10.1086/317451.PubMedGoogle Scholar
  34. 34.
    Rex JH, Bennett JE, Sugar AM, et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N Engl J Med. 1994;331:1325–30. doi:10.1056/NEJM199411173312001.PubMedGoogle Scholar
  35. 35.
    Anaissie EJ, Darouiche RO, Abi-Said D, et al. Management of invasive candidal infections: results of a prospective, randomized, multicenter study of fluconazole versus amphotericin B and review of the literature. Clin Infect Dis. 1996;23:964–72.PubMedGoogle Scholar
  36. 36.
    Phillips P, Shafran S, Garber G, et al. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis. 1997;16(5):337–45. doi:10.1007/BF01726360.PubMedGoogle Scholar
  37. 37.
    Kuse ER, Chetchotisakd P, da Cunha CA, et al. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomized double-blind trial. Lancet. 2007;369(9572):1519–27. doi:10.1016/S0140-6736(07)60605-9.PubMedGoogle Scholar
  38. 38.
    Cornely OA, Maertens J, Bresnik M, et al. Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). Clin Infect Dis. 2007;44:1289–97. doi:10.1086/514341.PubMedGoogle Scholar
  39. 39.
    Larkin J, Montero J. Efficacy and safety of amphotericin B lipid complex for zygomycosis. Infect Med. 2003;20:201–6.Google Scholar
  40. 40.
    Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327–60. doi:10.1086/525258.PubMedGoogle Scholar
  41. 41.
    Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004;38(2):161–89. doi:10.1086/380796.PubMedGoogle Scholar
  42. 42.
    Chapman SW, Dismukes WE, Proia LA, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(12):1801–12. doi:10.1086/588300.PubMedGoogle Scholar
  43. 43.
    Chamilos G, Lewis RE, Kontoyiannis DP. Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis. Clin Infect Dis. 2008;47:503–9. doi:10.1086/590004.PubMedGoogle Scholar
  44. 44.
    Andes D, Stamsted T, Conklin R. Pharmacodynamics of amphotericin B in a neutropenic-mouse disseminated-candidiasis model. Antimicrob Agents Chemother. 2001;45:922–6. doi:10.1128/AAC.45.3.922-926.2001.PubMedGoogle Scholar
  45. 45.
    Klepser ME, Wolfe EJ, Jones RN, et al. Antifungal pharmacodynamic characteristics of fluconazole and amphotericin B tested against Candida albicans. Antimicrob Agents Chemother. 1997;41:1392–5.PubMedGoogle Scholar
  46. 46.
    Cagnoni PJ, Walsh TJ, Prendergast MM, et al. Pharmacoeconomic analysis of liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients. J Clin Oncol. 2000;18(12):2476–83.PubMedGoogle Scholar
  47. 47.
    Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992;326:845–51.PubMedGoogle Scholar
  48. 48.
    Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation—a prospective, randomized, double-blind study. J Infect Dis. 1995;171:1545–52.PubMedGoogle Scholar
  49. 49.
    Marr KA, Seidel MA, Slavin RA, et al. Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial. Blood. 2000;96:2055–61.PubMedGoogle Scholar
  50. 50.
    Alexander BD, Schell WA, Miller JL, et al. Candida glabrata fungemia in transplant patients receiving voriconazole after fluconazole. Transplantation. 2005;80:868–71. doi:10.1097/01.tp.0000173771.47698.7b.PubMedGoogle Scholar
  51. 51.
    Slain D, Rogers PD, Cleary JD, Chapman SW. Intravenous itraconazole. Ann Pharmacother. 2001;35:720–9. doi:10.1345/aph.10262.PubMedGoogle Scholar
  52. 52.
    Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clin Infect Dis. 2003;36:630–7. doi:10.1086/367933.PubMedGoogle Scholar
  53. 53.
    VFend® (voriconazole). Prescribing information. New York, NY, USA: Pfizer Pharmaceuticals; 2008.Google Scholar
  54. 54.
    Leveque D, Nivoix Y, Jehl F, Herbrecht R. Clinical pharmacokinetics of voriconazole. Int J Antimicrob Agents. 2006;27:274–84. doi:10.1016/j.ijantimicag.2006.01.003.PubMedGoogle Scholar
  55. 55.
    Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005;366(9495):1435–42. doi:10.1016/S0140-6736(05)67490-9.PubMedGoogle Scholar
  56. 56.
    Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408–15. doi:10.1056/NEJMoa020191.PubMedGoogle Scholar
  57. 57.
    Vehreschild JJ, Bohme A, Buchheidt D, et al. A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). J Infect. 2007;55:445–9. doi:10.1016/j.jinf.2007.07.003.PubMedGoogle Scholar
  58. 58.
    Siwek GT, Pfaller MA, Polgreen PM, et al. Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell transplant patients receiving voriconazole prophylaxis. Diagn Microbiol Infect Dis. 2006;55:209–12. doi:10.1016/j.diagmicrobio.2006.01.018.PubMedGoogle Scholar
  59. 59.
    Wingard JR, et al. Prospective, multicenter study comparing voriconazole with fluconazole as prophylaxis in allogeneic stem cell recipients. In: Annual meeting of American society of hematology, Atlanta, Georgia; 2007, Abstract #163.Google Scholar
  60. 60.
    Siwek GT, Dodgson KJ, de Magalhaes-Silverman M, et al. Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis. Clin Infect Dis. 2004;39:584–7. doi:10.1086/422723.PubMedGoogle Scholar
  61. 61.
    Imhof A, Balajee SA, Fredricks DN, et al. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis. 2004;39:743–6. doi:10.1086/423274.PubMedGoogle Scholar
  62. 62.
    Vigouroux S, Morin O, Moreau P, et al. Zygomycosis after prolonged use of voriconazole in immunocompromised patients with hematologic disease: attention required. Clin Infect Dis. 2005;40:e35–7. doi:10.1086/427752.PubMedGoogle Scholar
  63. 63.
    Trifilio S, Singhal S, Williams S, et al. Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole. Bone Marrow Transplant. 2007;40:451–6. doi:10.1038/sj.bmt.1705754.PubMedGoogle Scholar
  64. 64.
    Shao PL, Huang LM, Hsueh PR. Recent advances and challenges in the treatment of invasive fungal infections. Int J Antimicrob Agents. 2007;30:487–95. doi:10.1016/j.ijantimicag.2007.07.019.PubMedGoogle Scholar
  65. 65.
    Marr KA, Leisenring W, Crippa F, et al. Cyclophosphamide metabolism is affected by azole antifungals. Blood. 2004;103(4):1557–9. doi:10.1182/blood-2003-07-2512.PubMedGoogle Scholar
  66. 66.
    Drew R. Potential role of aerosolized amphotericin B formulations in the prevention and adjunctive treatment of invasive fungal infections. Int J Antimicrob Agents. 2006;27S:S36–44. doi:10.1016/j.ijantimicag.2006.03.018.Google Scholar
  67. 67.
    Pascual A, Calandra T, Bolay S, et al. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis. 2008;46:201–11. doi:10.1086/524669.PubMedGoogle Scholar
  68. 68.
    Goodwin M, Drew RH. Antifungal serum concentration monitoring: an update. J Antimicrob Chemother. 2008;61:17–25. doi:10.1093/jac/dkm389.PubMedGoogle Scholar
  69. 69.
    Smith J, Safdar N, Knasinski V, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006;50(4):1570–2. doi:10.1128/AAC.50.4.1570-1572.2006.PubMedGoogle Scholar
  70. 70.
    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. doi:10.1086/324620.PubMedGoogle Scholar
  71. 71.
    Trifilio S, Pennick G, Pi J, et al. Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients. Cancer. 2007;109(8):1532–5. doi:10.1002/cncr.22568.PubMedGoogle Scholar
  72. 72.
    Tan K, Brayshaw N, Tomaszewski K, et al. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol. 2006;46:235–43. doi:10.1177/0091270005283837.PubMedGoogle Scholar
  73. 73.
    Ezzet F, Wexler D, Courtney R, et al. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin Pharmacokinet. 2005;44:211–20. doi:10.2165/00003088-200544020-00006.PubMedGoogle Scholar
  74. 74.
    Noxafil® (posaconazole). Prescribing information. Kenilworth, NJ, USA: Schering Corporation.Google Scholar
  75. 75.
    Walsh TJ, Raad I, Patterson TF, et al. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin Infect Dis. 2007;44:2–12. doi:10.1086/508774.PubMedGoogle Scholar
  76. 76.
    van Burik JA, Hare RS, Solomon HF, et al. Posaconazole is effective as salvage therapy in zygomycosis: a retrospective summary of 91 cases. Clin Infect Dis. 2006;42:e61–5. doi:10.1086/500212.PubMedGoogle Scholar
  77. 77.
    Greenberg RN, Mullane K, van Burik JA, et al. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother. 2006;50:126–33. doi:10.1128/AAC.50.1.126-133.2006.PubMedGoogle Scholar
  78. 78.
    Courtney R, Wexler D, Radwanski E, et al. Effect of food on the relative bioavailability of two oral formulations of posaconazole in healthy adults. Br J Clin Pharmacol. 2004;57:218–22. doi:10.1046/j.1365-2125.2003.01977.x.PubMedGoogle Scholar
  79. 79.
    Ullmann AJ, Lipton JH, Vesole DH, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007;356:335–47. doi:10.1056/NEJMoa061098.PubMedGoogle Scholar
  80. 80.
    Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs fluconazole or itraconazole prophylaxis in patients with neutropenia. N Eng J Med. 2007;356:348–59. doi:10.1056/NEJMoa061094.Google Scholar
  81. 81.
    Ibrahim AS, Gebremariam T, Schwartz JA, et al. Posaconazole mono- or combination therapy for the treatment of murine zygomycosis. Antimicrob Agents Chemother 2008; doi:10.1128/AAC.01124-08.
  82. 82.
    Vazquez JA, Skiest DJ, Nieto L, et al. A multicenter randomized trial evaluating posaconazole versus fluconazole for the treatment of oropharyngeal candidiasis in subjects with HIV/AIDS. Clin Infect Dis. 2006;42:1179–86. doi:10.1086/501457.PubMedGoogle Scholar
  83. 83.
    Raad II, Graybill JR, Bustamante AB, et al. Safety of long-term oral posaconazole use in the treatment of refractory invasive fungal infections. Clin Infect Dis. 2006;42:1726–34. doi:10.1086/504328.PubMedGoogle Scholar
  84. 84.
    Wexler D, Courtney R, Richards W, et al. Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study. Eur J Pharm Sci. 2004;21:645–53. doi:10.1016/j.ejps.2004.01.005.PubMedGoogle Scholar
  85. 85.
    Krishna G, Parsons A, Kantesaria B, Mant T. Evaluation of the pharmacokinetics of posaconazole and rifabutin following co-administration to healthy men. Curr Med Res Opin. 2007;23:545–52. doi:10.1185/030079906X167507.PubMedGoogle Scholar
  86. 86.
    Krishna G, Sansone-Parsons A, Kantesaria B. Drug interaction assessment following concomitant administration of posaconazole and phenytoin in healthy men. Curr Med Res Opin. 2007;23:1415–22. doi:10.1185/030079907X187937.PubMedGoogle Scholar
  87. 87.
    Sansone-Parsons A, Krishna G, Martinho M, et al. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy. 2007;27:825–34. doi:10.1592/phco.27.6.825.PubMedGoogle Scholar
  88. 88.
    Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis. 2008;47:364–71. doi:10.1086/589857.PubMedGoogle Scholar
  89. 89.
    Katiyar S, Pfaller M, Edlind T. Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandins susceptibility. Antimicrob Agents Chemother. 2006;50:2892–4. doi:10.1128/AAC.00349-06.PubMedGoogle Scholar
  90. 90.
    Cleary JD, Garcia-Effron G, Chapman SW, Perlin DS. Reduced Candida glabrata susceptibility secondary to an FKS1 mutation developed during candidemia treatment. Antimicrob Agents Chemother. 2008;52:2263–5. doi:10.1128/AAC.01568-07.PubMedGoogle Scholar
  91. 91.
    Krogh-Madsen M, Arendrup MC, Heslet L, Knudsen JD. Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin Infect Dis. 2006;42:938–44. doi:10.1086/500939.PubMedGoogle Scholar
  92. 92.
    Cancidas® (caspofungin). Prescribing information. Whitehouse Station, NJ, USA: Merck & Co., Inc.Google Scholar
  93. 93.
    Eraxis™ (anidulafungin). Prescribing information. New York, NY, USA: Pfizer Inc.Google Scholar
  94. 94.
    Mycamine® (micafungin). Prescribing information. Deerfield, IL, USA: Astellas Pharma US, Inc.Google Scholar
  95. 95.
    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. doi:10.1056/NEJMoa021585.PubMedGoogle Scholar
  96. 96.
    Reboli AC, Rotstein C, Pappas PG, et al. Anidulafungin versus fluconazole for invasive candidiasis. N Eng J Med. 2007;356:2472–82. doi:10.1056/NEJMoa066906.Google Scholar
  97. 97.
    Pappas PG, Rotstein CM, Betts RF, et al. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007;45:883–93. doi:10.1086/520980.PubMedGoogle Scholar
  98. 98.
    Cornely OA, Lasso M, Betts R, et al. Caspofungin for the treatment of less common forms of invasive candidiasis. J Antimicrob Chemother. 2007;60:363–9. doi:10.1093/jac/dkm169.PubMedGoogle Scholar
  99. 99.
    Cornely OA, Sidhu M, Odeyemi I, et al. Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany. Curr Med Res Opin. 2008;24:1743–53. doi:10.1185/03007990802124889.PubMedGoogle Scholar
  100. 100.
    Ostrosky-Zeichner L, Pappas PG. Invasive candidiasis in the intensive care unit. Crit Care Med. 2006;34:857–63. doi:10.1097/01.CCM.0000201897.78123.44.PubMedGoogle Scholar
  101. 101.
    Maertens J, Raad I, Petrikkos G, et al. Efficacy and safety of caspofungin for the treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004;39:1563–71. doi:10.1086/423381.PubMedGoogle Scholar
  102. 102.
    Kartsonis NA, Saah AJ, Lipka C, et al. Salvage therapy with caspofungin for treatment of invasive aspergillosis: results from the caspofungin use study. J Infect. 2005;50:196–205. doi:10.1016/j.jinf.2004.05.011.PubMedGoogle Scholar
  103. 103.
    Denning DW, Marr KA, Lau WM, et al. Micafungin (FK463), alone or in combination with other systemic antifungal agents, for the treatment of acute invasive aspergillosis. J Infect. 2006;53:337–49. doi:10.1016/j.jinf.2006.03.003.PubMedGoogle Scholar
  104. 104.
    Cappelletty D, Eiselstein-McKitrick K. The echinocandins. Pharmacotherapy. 2007;27(3):369–88. doi:10.1592/phco.27.3.369.PubMedGoogle Scholar
  105. 105.
    Bennett JE. Echinocandins for candidemia in adults without neutropenia. N Engl J Med. 2006;355(11):1154–9. doi:10.1056/NEJMct060052.PubMedGoogle Scholar
  106. 106.
    Sanz-Rodriquez C, Lopez-Duarte M, Jurado M, et al. Safety of the concomitant use of caspofungin and cyclosporin A in patients with invasive fungal infections. Bone Marrow Transplant. 2004;34:13–20. doi:10.1038/sj.bmt.1704516.Google Scholar
  107. 107.
    Saner F, Gensicke J, Rath P, et al. Safety profile of concomitant use of caspofungin and cyclosporine or tacrolimus in liver transplant patients. Infection. 2006;34:328–32. doi:10.1007/s15010-006-5657-8.PubMedGoogle Scholar
  108. 108.
    Hebert MF, Townsend RW, Austin S, et al. Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers. J Clin Pharmacol. 2005;45:954–60. doi:10.1177/0091270005278601.PubMedGoogle Scholar
  109. 109.
    Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med. 1979;301:126–31.PubMedGoogle Scholar
  110. 110.
    Dismukes WE, Cloud G, Gallis HA, et al. Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks. N Eng J Med. 1987;317:334–41.CrossRefGoogle Scholar
  111. 111.
    van der Horst CM, Saag MS, Cloud GA, et al. Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. N Engl J Med. 1997;337:15–21. doi:10.1056/NEJM199707033370103.PubMedGoogle Scholar
  112. 112.
    Brouwer AE, Rajanuwong A, Chierakul W, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial. Lancet. 2004;363:1764–7. doi:10.1016/S0140-6736(04)16301-0.PubMedGoogle Scholar
  113. 113.
    Bicanic T, Wood R, Meintjes T, et al. High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial. Clin Infect Dis. 2008;47:123–30. doi:10.1086/588792.PubMedGoogle Scholar
  114. 114.
    Rex JH, Pappas PG, Karchmer AW, et al. A randomize and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects. Clin Infect Dis. 2003;36:1221–8. doi:10.1086/374850.PubMedGoogle Scholar
  115. 115.
    Ostrosky-Zeichner L, Kontoyiannis D, Raffalli J, et al. International, open-label, noncomparative, clinical trial of micafungin alone and in combination for treatment of newly diagnosed and refractory candidemia. Eur J Clin Microbiol Infect Dis. 2005;24:654–61. doi:10.1007/s10096-005-0024-8.PubMedGoogle Scholar
  116. 116.
    Marr KA, Boeckh M, Carter RA, et al. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004;39:797–802. doi:10.1086/423380.PubMedGoogle Scholar
  117. 117.
    Kontoyiannis DP, Hachem R, Lewis RE, et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003;98:292–9. doi:10.1002/cncr.11479.PubMedGoogle Scholar
  118. 118.
    Singh N, Limaye AP, Forrest G, et al. Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation. 2006;81:320–6. doi:10.1097/01.tp.0000202421.94822.f7.PubMedGoogle Scholar
  119. 119.
    Maertens J, Glasmacher A, Herbrecht R, et al. Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer. 2006;107:2888–97. doi:10.1002/cncr.22348.PubMedGoogle Scholar
  120. 120.
    Caillot D, Thiebaut A, Herbrecht R, et al. Liposomal amphotericin B in combination with caspofungin for invasive aspergillosis in patients with hematologic malignancies: a randomized pilot study (Combistrat trial). Cancer. 2007;110:2740–6. doi:10.1002/cncr.23109.PubMedGoogle Scholar
  121. 121.
    Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis. 2007;7(6):395–401. doi:10.1016/S1473-3099(07)70085-3.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Dustin T. Wilson
    • 1
    • 2
  • Richard H. Drew
    • 1
    • 2
  • John R. Perfect
    • 1
  1. 1.Division of Infectious Diseases, Department of MedicineDuke University Medical CenterDurhamUSA
  2. 2.Campbell University School of PharmacyBuies CreekUSA

Personalised recommendations