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Fungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies

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Principles and Practice of Cancer Infectious Diseases

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Recent advances in hematopoietic cell ­transplantation and a broadening array of salvage chemotherapy options have extended the survival of patients with hematological cancers, but can result in prolonged periods of immunosuppression and susceptibility to invasive ­fungal infections. Among these high-risk patient populations, systemic antifungal therapy is administered episodically or sometimes continuously for months or even years, increasing concerns for the development of antifungal resistance. As newer triazoles (voriconazole and posaconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) have supplanted amphotericin B formulations as the preferred antifungal therapies for primary and secondary prophylaxis, pharmacokinetic variability inherent to the triazoles as well as emerging patterns of intrinsic and acquired antifungal resistance are becoming increasingly important factors in the long-term management of invasive fungal infections. In this chapter, we review recent data concerning antifungal drug resistance for these newer azoles and echinocandins, as well as key considerations in drug dosing.

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References

  1. Maertens J, Buve K, Anaissie E. Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for invasive mold infections: counterpoint. J Natl Compr Canc Netw. 2008;6:183–9.

    PubMed  Google Scholar 

  2. Krcmery V, Kalavsky E. Antifungal drug discovery, six new molecules patented after 10 years of feast: why do we need new patented drugs apart from new strategies? Recent Pat Antiinfect Drug Discov. 2007;2:182–7.

    PubMed  CAS  Google Scholar 

  3. Bhatti Z, Shaukat A, Almyroudis NG, Segal BH. Review of epidemiology, diagnosis, and treatment of invasive mould infections in allogeneic hematopoietic stem cell transplant recipients. Mycopathologia. 2006;162:1–15.

    PubMed  Google Scholar 

  4. Chamilos G, Luna M, Lewis RE, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989-2003). Haematologica. 2006;91:986–9.

    PubMed  Google Scholar 

  5. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007;20:133–63.

    PubMed  CAS  Google Scholar 

  6. Warnock DW. Trends in the epidemiology of invasive fungal infections. Nippon Ishinkin Gakkai Zasshi. 2007;48:1–12.

    Google Scholar 

  7. Maschmeyer G, Haas A. The epidemiology and treatment of infections in cancer patients. Int J Antimicrob Agents. 2008;31:193–7.

    PubMed  CAS  Google Scholar 

  8. Thursky KA, Worth LJ, Seymour JF, Miles Prince H, Slavin MA. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab*. Br J Haematol. 2006;132:3–12.

    PubMed  Google Scholar 

  9. Elter T, Vehreschild JJ, Gribben J, Cornely OA, Engert A, Hallek M. Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab. Ann Hematol. 2009;88:121–32.

    PubMed  CAS  Google Scholar 

  10. 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.

    PubMed  CAS  Google Scholar 

  11. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44:531–40.

    PubMed  Google Scholar 

  12. Fukuda T, Boeckh M, Carter RA, et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood. 2003;102:827–33.

    PubMed  CAS  Google Scholar 

  13. Garcia-Vidal C, Upton A, Kirby KA, Marr KA. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis. 2008;47:1041–50.

    PubMed  Google Scholar 

  14. 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.

    PubMed  CAS  Google Scholar 

  15. Kontoyiannis DP, Lewis RE. Antifungal drug resistance of pathogenic fungi. Lancet. 2002;359:1135–44.

    PubMed  CAS  Google Scholar 

  16. 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.

    PubMed  Google Scholar 

  17. Kontoyiannis DP, Lewis RE. Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management. Infect Dis Clin North Am. 2006;20:581–607, vi.

    Google Scholar 

  18. Malani AN, Kauffman CA. Changing epidemiology of rare mould infections: implications for therapy. Drugs. 2007;67:1803–12.

    PubMed  CAS  Google Scholar 

  19. Brown J. Zygomycosis: an emerging fungal infection. Am J Health Syst Pharm. 2005;62:2593–6.

    PubMed  Google Scholar 

  20. Snelders E, van der Lee HA, Kuijpers J, et al. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 2008;5:e219.

    PubMed  Google Scholar 

  21. Howard SJ, Webster I, Moore CB, et al. Multi-azole resistance in Aspergillus fumigatus. Int J Antimicrob Agents. 2006;28:450–3.

    PubMed  CAS  Google Scholar 

  22. Mellado E, Garcia-Effron G, Alcazar-Fuoli L, et al. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother. 2007;51:1897–904.

    PubMed  CAS  Google Scholar 

  23. Verweij PE, Mellado E, Melchers WJ. Multiple-triazole-resistant aspergillosis. N Engl J Med. 2007;356:1481–3.

    PubMed  CAS  Google Scholar 

  24. White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev. 1998;11:382–402.

    PubMed  CAS  Google Scholar 

  25. Liu TT, Lee RE, Barker KS, Wei L, Homayouni R, Rogers PD. Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans. Antimicrob Agents Chemother. 2005;49:2226–36.

    PubMed  CAS  Google Scholar 

  26. White TC. Mechanisms of resistance to antifungal agents. In: Murray PR, Baron EJ, Jorgensen JH, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 8th ed. Washington, DC: ASM Press; 2003. p. 1869–79.

    Google Scholar 

  27. Sheehan DJ, Hitchcock CA, Sibley CM. Current and emerging azole antifungal agents. Clin Microbiol Rev. 1999;12:40–79.

    PubMed  CAS  Google Scholar 

  28. Groll AH, Piscitelli SC, Walsh TJ. Clinical pharmacology of ­systemic antifungal agents: a comprehensive review of agents in clinical use, current investigational compounds, and putative ­targets for antifungal drug development. Adv Pharmacol. 1998;44:343–499.

    PubMed  CAS  Google Scholar 

  29. Gubbins PO, McConnell SA, Amsden JR. Antifungal agents. In: Piscitelli SC, Rodvold KA, editors. Drug interactions in infectious diseases. 2nd ed. Totowa, NJ: Humana; 2005. p. 289–338.

    Google Scholar 

  30. Smith G, Stubbins MJ, Harries LW, Wolf CR. Molecular genetics of the human cytochrome P450 monooxygenase superfamily. Xenobiotica. 1998;28:1129–65.

    PubMed  CAS  Google Scholar 

  31. Lewis RE, editor. Antifungal drug interactions. Washington, DC: ASM Press; 2009.

    Google Scholar 

  32. Lewis RE. Managing drug interactions in the patient with aspergillosis. Med Mycol. 2006;44(suppl):349–56.

    Google Scholar 

  33. Purkins L, Wood N, Ghahramani P, Greenhalgh K, Allen MJ, Kleinermans D. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens. Antimicrob Agents Chemother. 2002;46:2546–53.

    PubMed  CAS  Google Scholar 

  34. Lazarus HM, Blumer JL, Yanovich S, Schlamm H, Romero A. Safety and pharmacokinetics of oral voriconazole in patients at risk of fungal infection: a dose escalation study. J Clin Pharmacol. 2002;42:395–402.

    PubMed  CAS  Google Scholar 

  35. Hyland R, Jones BC, Smith DA. Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos. 2003;31:540–7.

    PubMed  CAS  Google Scholar 

  36. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother. 2009;53:24–34.

    PubMed  CAS  Google Scholar 

  37. Ikeda Y, Umemura K, Kondo K, Sekiguchi K, Miyoshi S, Nakashima M. Pharmacokinetics of voriconazole and cytochrome P450 2C19 genetic status. Clin Pharmacol Ther. 2004;75:587–8.

    PubMed  CAS  Google Scholar 

  38. Trifilio S, Ortiz R, Pennick G, et al. Voriconazole therapeutic drug monitoring in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2005;35:509–13.

    PubMed  CAS  Google Scholar 

  39. 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;109:1532–5.

    PubMed  CAS  Google Scholar 

  40. 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.

    PubMed  CAS  Google Scholar 

  41. Trifilio SM, Yarnold PR, Scheetz MH, Pi J, Pennick G, Mehta J. Serial plasma voriconazole concentrations after allogeneic hematopoietic stem cell transplantation. Antimicrob Agents Chemother. 2009;53(5):1793–6.

    PubMed  CAS  Google Scholar 

  42. Walsh TJ, Karlsson MO, Driscoll T, et al. Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob Agents Chemother. 2004;48:2166–72.

    PubMed  CAS  Google Scholar 

  43. Pasqualotto AC, Shah M, Wynn R, Denning DW. Voriconazole plasma monitoring. Arch Dis Child. 2008;93:578–81.

    PubMed  CAS  Google Scholar 

  44. Smith J, Safdar N, Knasinski V, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006;50:1570–2.

    PubMed  CAS  Google Scholar 

  45. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves safety and efficacy outcomes. Clin Infect Dis. 2007;46:201–11.

    Google Scholar 

  46. Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. 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.

    PubMed  CAS  Google Scholar 

  47. Scherpbier HJ, Hilhorst MI, Kuijpers TW. Liver failure in a child receiving highly active antiretroviral therapy and voriconazole. Clin Infect Dis. 2003;37:828–30.

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  49. Courtney R, Sansone A, Smith W, et al. Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease. J Clin Pharmacol. 2005;45:185–92.

    PubMed  CAS  Google Scholar 

  50. Gubbins PO, Krishna G, Sansone-Parsons A, et al. Pharmacokinetics and safety of oral posaconazole in neutropenic stem cell transplant recipients. Antimicrob Agents Chemother. 2006;50:1993–9.

    PubMed  CAS  Google Scholar 

  51. Krishna G, Martinho M, Chandrasekar P, Ullmann AJ, Patino H. Pharmacokinetics of oral posaconazole in allogeneic hematopoietic stem cell transplant recipients with graft-versus-host disease. Pharmacotherapy. 2007;27:1627–36.

    PubMed  CAS  Google Scholar 

  52. 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.

    PubMed  CAS  Google Scholar 

  53. Lewis R, Hogan H, Howell A, Safdar A. Progressive fusariosis: unpredictable posaconazole bioavailability, and feasibility of recombinant interferon-gamma plus granulocyte macrophage-colony stimulating factor for refractory disseminated infection. Leuk Lymphoma. 2008;49:163–5.

    PubMed  CAS  Google Scholar 

  54. Ullmann AJ, Cornely OA, Burchardt A, et al. Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection. Antimicrob Agents Chemother. 2006;50:658–66.

    PubMed  CAS  Google Scholar 

  55. Courtney R, Radwanski E, Lim J, Laughlin M. Pharmacokinetics of posaconazole coadministered with antacid in fasting or nonfasting healthy men. Antimicrob Agents Chemother. 2004;48:804–8.

    PubMed  CAS  Google Scholar 

  56. 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.

    PubMed  CAS  Google Scholar 

  57. 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.

    PubMed  CAS  Google Scholar 

  58. Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.

    PubMed  CAS  Google Scholar 

  59. Betts R, Glasmacher A, Maertens J, et al. Efficacy of caspofungin against invasive Candida or invasive Aspergillus infections in neutropenic patients. Cancer. 2006;106:466–73.

    PubMed  CAS  Google Scholar 

  60. Wagner C, Graninger W, Presterl E, Joukhadar C. The echinocandins: comparison of their pharmacokinetics, pharmacodynamics and clinical applications. Pharmacology. 2006;78:161–77.

    PubMed  CAS  Google Scholar 

  61. Wiederhold NP, Lewis RE. The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy. Expert Opin Investig Drugs. 2003;12:1313–33.

    PubMed  CAS  Google Scholar 

  62. Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. In vitro activities of anidulafungin against more than 2,500 clinical isolates of Candida spp., including 315 isolates resistant to fluconazole. J Clin Microbiol. 2005;43:5425–7.

    PubMed  CAS  Google Scholar 

  63. Kurtz MB, Heath IB, Marrinan J, Dreikorn S, Onishi J, Douglas C. Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1, 3)-beta-D-glucan synthase. Antimicrob Agents Chemother. 1994;38:1480–9.

    PubMed  CAS  Google Scholar 

  64. 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.

    PubMed  CAS  Google Scholar 

  65. 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.

    PubMed  CAS  Google Scholar 

  66. Warn PA, Morrissey G, Morrissey J, Denning DW. 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.

    PubMed  CAS  Google Scholar 

  67. Hohl TM, Feldmesser M, Perlin DS, Pamer EG. Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal beta-glucan exposure. J Infect Dis. 2008;198(2):176–85.

    PubMed  CAS  Google Scholar 

  68. Lamaris GA, Lewis RE, Chamilos G, et al. Caspofungin-mediated beta-glucan unmasking and enhancement of human polymorphonuclear neutrophil activity against Aspergillus and non-Aspergillus hyphae. J Infect Dis. 2008;198:186–92.

    PubMed  CAS  Google Scholar 

  69. Wheeler RT, Kombe D, Agarwala SD, Fink GR. Dynamic, morphotype-specific Candida albicans beta-glucan exposure during infection and drug treatment. PLoS Pathog. 2008;4:e1000227.

    PubMed  Google Scholar 

  70. Wheeler RT, Fink GR. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog. 2006;2:e35.

    PubMed  Google Scholar 

  71. Uchida K, Nishiyama Y, Yokota N, Yamaguchi H. In vitro antifungal activity of a novel lipopeptide antifungal agent, FK463, against various fungal pathogens. J Antibiot (Tokyo). 2000;53:1175–81.

    CAS  Google Scholar 

  72. Espinel-Ingroff A. In vitro antifungal activities of anidulafungin and micafungin, licensed agents and the investigational triazole posaconazole as determined by NCCLS methods for 12,052 fungal isolates: review of the literature. Rev Iberoam Micol. 2003;20:121–36.

    PubMed  Google Scholar 

  73. Balajee SA, Gribskov JL, Hanley E, Nickle D, Marr KA. Aspergillus lentulus sp. nov., a new sibling species of A. fumigatus. Eukaryot Cell. 2005;4:625–32.

    PubMed  CAS  Google Scholar 

  74. Chryssanthou E, Cuenca-Estrella M. Comparison of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antibiotic Susceptibility Testing proposed standard and the E-test with the NCCLS broth microdilution method for voriconazole and caspofungin susceptibility testing of yeast species. J Clin Microbiol. 2002;40:3841–4.

    PubMed  CAS  Google Scholar 

  75. Cuenca-Estrella M, Lee-Yang W, Ciblak MA, et al. Comparative evaluation of NCCLS M27-A and EUCAST broth microdilution procedures for antifungal susceptibility testing of Candida species. Antimicrob Agents Chemother. 2002;46:3644–7.

    PubMed  CAS  Google Scholar 

  76. Pfaller MA, Boyken L, Hollis RJ, et al. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J Clin Microbiol. 2008;46:150–6.

    PubMed  CAS  Google Scholar 

  77. Kartsonis N, Killar J, Mixson L, et al. Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis: relationship of MIC to treatment outcome. Antimicrob Agents Chemother. 2005;49:3616–23.

    PubMed  CAS  Google Scholar 

  78. Pfaller MA, Diekema DJ, Rinaldi MG, et al. Results from the ARTEMIS DISK Global Antifungal Surveillance Study: a 6.5-year analysis of susceptibilities of Candida and other yeast species to fluconazole and voriconazole by standardized disk diffusion testing. J Clin Microbiol. 2005;43:5848–59.

    PubMed  CAS  Google Scholar 

  79. Pfaller MA, Diekema DJ, Ostrosky-Zeichner L, et al. Correlation of MIC with outcome for Candida species tested against caspofungin, anidulafungin, and micafungin: analysis and proposal for interpretive MIC breakpoints. J Clin Microbiol. 2008;46(8):2620–9.

    PubMed  CAS  Google Scholar 

  80. Andes DR, Diekema DJ, Pfaller MA, Marchillo K, Bohrmueller J. In vivo pharmacodynamic target investigation for micafungin against Candida albicans and C. glabrata in a neutropenic murine candidiasis model. Antimicrob Agents Chemother. 2008;52:3497–503.

    PubMed  CAS  Google Scholar 

  81. Wiederhold NP, Lewis II JS. The echinocandin micafungin: a review of the pharmacology, spectrum of activity, clinical efficacy and safety. Expert Opin Pharmacother. 2007;8:1155–66.

    PubMed  CAS  Google Scholar 

  82. Odabasi Z, Paetznick V, Rex JH, Ostrosky-Zeichner L. Effects of serum on in vitro susceptibility testing of echinocandins. Antimicrob Agents Chemother. 2007;51:4214–6.

    PubMed  CAS  Google Scholar 

  83. Paderu P, Garcia-Effron G, Balashov S, Delmas G, Park S, Perlin DS. Serum differentially alters the antifungal properties of ­echinocandin drugs. Antimicrob Agents Chemother. 2007;51:2253–6.

    PubMed  CAS  Google Scholar 

  84. Wiederhold NP, Najvar LK, Bocanegra R, Molina D, Olivo M, Graybill JR. In vivo efficacy of anidulafungin and caspofungin against Candida glabrata and association with in vitro potency in the presence of sera. Antimicrob Agents Chemother. 2007;51:1616–20.

    PubMed  CAS  Google Scholar 

  85. Moudgal V, Little T, Boikov D, Vazquez JA. Multiechinocandin- and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother. 2005;49:767–9.

    PubMed  CAS  Google Scholar 

  86. Park S, Kelly R, Kahn JN, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother. 2005;49:3264–73.

    PubMed  CAS  Google Scholar 

  87. Katiyar S, Pfaller M, Edlind T. Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob Agents Chemother. 2006;50:2892–4.

    PubMed  CAS  Google Scholar 

  88. Laverdiere M, Lalonde RG, Baril JG, Sheppard DC, Park S, Perlin DS. Progressive loss of echinocandin activity following prolonged use for treatment of Candida albicans oesophagitis. J Antimicrob Chemother. 2006;57:705–8.

    PubMed  CAS  Google Scholar 

  89. Miller CD, Lomaestro BW, Park S, Perlin DS. Progressive esophagitis caused by Candida albicans with reduced susceptibility to caspofungin. Pharmacotherapy. 2006;26:877–80.

    PubMed  Google Scholar 

  90. Kahn JN, Garcia-Effron G, Hsu MJ, Park S, Marr KA, Perlin DS. Acquired echinocandin resistance in a Candida krusei isolate due to modification of glucan synthase. Antimicrob Agents Chemother. 2007;51:1876–8.

    PubMed  Google Scholar 

  91. 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.

    PubMed  CAS  Google Scholar 

  92. Desnos-Ollivier M, Bretagne S, Raoux D, Hoinard D, Dromer F, Dannaoui E. Mutations in the fks1 gene in Candida albicans, C. tropicalis, and C. krusei correlate with elevated caspofungin MICs uncovered in AM3 medium using the method of the European Committee on Antibiotic Susceptibility Testing. Antimicrob Agents Chemother. 2008;52:3092–8.

    PubMed  CAS  Google Scholar 

  93. Thompson III GR, Wiederhold NP, Vallor AC, Villareal NC, Lewis II JS, Patterson TF. Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother. 2008;52:3783–5.

    PubMed  CAS  Google Scholar 

  94. Wiederhold NP, Grabinski JL, Garcia-Effron G, Perlin DS, Lee SA. Pyrosequencing to detect mutations in FKS1 that confer reduced echinocandin susceptibility in Candida albicans. Antimicrob Agents Chemother. 2008;52:4145–8.

    PubMed  CAS  Google Scholar 

  95. Wetzstein GA, Green MR, Greene JN. Mould breakthrough in immunosuppressed adults receiving anidulafungin: a report of 2 cases. J Infect. 2007;55:e131–3.

    PubMed  Google Scholar 

  96. Arendrup MC, Garcia-Effron G, Buzina W, et al. Breakthrough Aspergillus fumigatus and Candida albicans double infection during caspofungin treatment: laboratory characteristics and implication for susceptibility testing. Antimicrob Agents Chemother. 2009;53(3):1185–93.

    PubMed  CAS  Google Scholar 

  97. Niimi K, Maki K, Ikeda F, et al. Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob Agents Chemother. 2006;50:1148–55.

    PubMed  CAS  Google Scholar 

  98. Perlin DS. Resistance to echinocandin-class antifungal drugs. Drug Resist Updat. 2007;10:121–30.

    PubMed  CAS  Google Scholar 

  99. Garcia-Effron G, Park S, Perlin DS. Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother. 2009;53:112–22.

    PubMed  CAS  Google Scholar 

  100. Bennett JE. Echinocandins for candidemia in adults without neutropenia. N Engl J Med. 2006;355:1154–9.

    PubMed  CAS  Google Scholar 

  101. Forrest GN, Weekes E, Johnson JK. Increasing incidence of Candida parapsilosis candidemia with caspofungin usage. J Infect. 2008;56:126–9.

    PubMed  Google Scholar 

  102. Colombo AL, Nucci M, Park BJ, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. 2006;44:2816–23.

    PubMed  CAS  Google Scholar 

  103. Pfaller MA, Diekema DJ, Gibbs DL, et al. Geographic and temporal trends in isolation and antifungal susceptibility of Candida parapsilosis: a global assessment from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J Clin Microbiol. 2008;46:842–9.

    PubMed  CAS  Google Scholar 

  104. Garcia-Effron G, Katiyar SK, Park S, Edlind TD, Perlin DS. A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother. 2008;52:2305–12.

    PubMed  CAS  Google Scholar 

  105. Rocha EM, Garcia-Effron G, Park S, Perlin DS. A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob Agents Chemother. 2007;51:4174–6.

    PubMed  CAS  Google Scholar 

  106. Arendrup MC, Fuursted K, Gahrn-Hansen B, et al. Semi-national surveillance of fungaemia in Denmark 2004-2006: increasing incidence of fungaemia and numbers of isolates with reduced azole susceptibility. Clin Microbiol Infect. 2008;14:487–94.

    PubMed  CAS  Google Scholar 

  107. Levin DE. Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 2005;69:262–91.

    PubMed  CAS  Google Scholar 

  108. Cowen LE, Lindquist S. Hsp90 potentiates the rapid evolution of new traits: drug resistance in diverse fungi. Science. 2005;309:2185–9.

    PubMed  CAS  Google Scholar 

  109. Stevens DA, Espiritu M, Parmar R. Paradoxical effect of caspofungin: reduced activity against Candida albicans at high drug concentrations. Antimicrob Agents Chemother. 2004;48:3407–11.

    PubMed  CAS  Google Scholar 

  110. Stevens DA, Ichinomiya M, Koshi Y, Horiuchi H. Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall ­chitin; evidence for beta-1, 6-glucan synthesis inhibition by caspofungin. Antimicrob Agents Chemother. 2006;50:3160–1.

    PubMed  CAS  Google Scholar 

  111. Chamilos G, Lewis RE, Albert N, Kontoyiannis DP. Paradoxical effect of echinocandins across Candida species in vitro: evidence for echinocandin-specific and Candida species-related differences. Antimicrob Agents Chemother. 2007;51:2257–9.

    PubMed  CAS  Google Scholar 

  112. Lewis RE, Albert ND, Kontoyiannis DP. Comparison of the dose-dependent activity and paradoxical effect of caspofungin and micafungin in a neutropenic murine model of invasive pulmonary aspergillosis. J Antimicrob Chemother. 2008;61: 1140–4.

    PubMed  CAS  Google Scholar 

  113. Clemons KV, Espiritu M, Parmar R, Stevens DA. Assessment of the paradoxical effect of caspofungin in therapy of candidiasis. Antimicrob Agents Chemother. 2006;50:1293–7.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Sciences and Administration, College of Pharmacy, University of Houston, Texas Medical Center Campus, 1441 Moursund Street, #424, Houston, TX, 77030, USA

    Russell E. Lewis

  2. Department of Infectious Disease, Infection Control, and Employee Health, The University of Texas/M.D. Anderson Cancer Center, Houston, TX, USA

    Russell E. Lewis

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  1. Russell E. Lewis
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  2. David S. Perlin
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Correspondence to Russell E. Lewis .

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  1. MD Anderson Cancer Center, Infectious Diseases Department, The University of Texas, 800 5th Avenue, Apt. 12-G, New York, 10065, New York, USA

    Amar Safdar

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Lewis, R.E., Perlin, D.S. (2011). Fungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies. In: Safdar, A. (eds) Principles and Practice of Cancer Infectious Diseases. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-644-3_28

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