Advertisement

Drug Resistance in Cryptococcus neoformans

  • Kimberly E. Hanson
  • Barbara D. Alexander
  • John Perfect
Part of the Infectious Disease book series (ID)

Cryptococcus neoformans is an encapsulated yeast known to cause disease in both immunosuppressed as well as seemingly immunocompetent hosts. The infection begins after inhalation of the yeast into the lung which may be followed by hematogenous spread to extrapulmonary tissue (1). The fi ve most common anatomic sites of cryptococcal involvement are the lungs, central nervous system (CNS), skin, prostate, and eye. Importantly, C. neoformans has a unique predilection for neural tissue and causes severe and often fatal meningoencephalitis. Most patients present themselves with subacute signs and symptoms of the central nervous system disease such as fever, headache, mental status changes, lethargy, or coma (1).

Keywords

Antimicrob Agent Cryptococcus Neoformans Cryptococcal Meningitis Solid Organ Transplant Recipient Cryptococcal Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mitchell TG, Perfect JR. Cryptococcosis in the era of AIDS – 100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 1995; 8(4):515–548PubMedGoogle Scholar
  2. 2.
    Sanati H, Messer SA, Pfaller M et al. Multicenter evaluation of broth microdilution method for susceptibility testing of Cryptococcus neoformans against fluconazole. J Clin Microbiol 1996; 34(5):1280–1282PubMedGoogle Scholar
  3. 3.
    Cuenca-Estrella M, Diaz-Guerra TM, Mellado E, Rodriguez-Tudela JL. Flucytosine primary resistance in Candida species and Cryptococcus neoformans. Eur J Clin Microbiol Infect Dis 2001; 20(4):276–279PubMedCrossRefGoogle Scholar
  4. 4.
    Orni-Wasserlauf R, Izkhakov E, Siegman-Igra Y, Bash E, Polacheck I, Giladi M. Fluconazole-resistant Cryptococcus neoformans isolated from an immunocompetent patient without prior exposure to fluconazole. Clin Infect Dis 1999; 29(6):1592–1593PubMedCrossRefGoogle Scholar
  5. 5.
    Armengou A, Porcar C, Mascaro J, Garcia-Bragado F. Possible development of resistance to fluconazole during suppressive therapy for AIDS-associated cryptococcal meningitis. Clin Infect Dis 1996; 23(6):1337–1338PubMedGoogle Scholar
  6. 6.
    Berg J, Clancy CJ, Nguyen MH. The hidden danger of primary flu-conazole prophylaxis for patients with AIDS. Clin Infect Dis 1998; 26(1):186–187PubMedCrossRefGoogle Scholar
  7. 7.
    Birley HDL, Johnson EM, Mcdonald P, Parry C, Carey PB, Warnock DW. Azole drug-resistance as a cause of clinical relapse in AIDS patients with cryptococcal meningitis. Int J STD AIDS 1995; 6(5):353–355PubMedGoogle Scholar
  8. 8.
    Currie BP, Ghannoum M, Bessen L, Casadevall A. Decreased fluconazole susceptibility of a relapse Cryptococcus neoform-ans isolate after fluconazole treatment. Inf Dis Clin Pract 1995; 4(4):318–319CrossRefGoogle Scholar
  9. 9.
    Friese G, Discher T, Fussle R, Schmalreck A, Lohmeyer J. Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease. AIDS 2001; 15(17):2344–2345PubMedCrossRefGoogle Scholar
  10. 10.
    Viard JP, Hennequin C, Fortineau N, Pertuiset N, Rothschild C, Zylberberg H. Fulminant cryptococcal infections in HIV-infected patients on oral fluconazole. Lancet 1995; 346(8967):118PubMedCrossRefGoogle Scholar
  11. 11.
    Block ER, Jennings AE, Bennett JE. 5-fluorocytosine resistance in Cryptococcus neoformans. Antimicrob Agents Chemotherapy 1973; 3(6):649–656Google Scholar
  12. 12.
    Walsh TJ. Echinocandins — an advance in the primary treatment of invasive candidiasis. N Engl J Med 2002; 347(25):2070–2072PubMedCrossRefGoogle Scholar
  13. 13.
    Perfect JR, Casadevall A. Cryptococcosis. Infect Dis Clin North Am 2002; 16(4):837PubMedCrossRefGoogle Scholar
  14. 14.
    Pappas PG, Perfect JR, Cloud GA et al. Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy. Clin Infect Dis 2001; 33(5):690–699PubMedCrossRefGoogle Scholar
  15. 15.
    Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: Variables influencing clinical characteristics and outcome. Emerg Infect Dis 2001; 7(3):375–381PubMedGoogle Scholar
  16. 16.
    Singh N, Alexander BD, Gupta KL. Characteristics and outcome of Cryptococcus neoformans infection of the central nervous system in organ transplant recipients: a prospective, multicenter study. 42nd ICAAC, 392, San Diego, CA, 2002Google Scholar
  17. 17.
    Robinson PA, Bauer M, Leal ME et al. Early mycological treatment failure in AIDS-associated cryptococcal meningitis. Clin Infect Dis 1999; 28(1):82–92PubMedCrossRefGoogle Scholar
  18. 18.
    Diamond RD, Bennett JE. Prognostic factors in cryptococ-cal meningitis. A study in 111 cases. Ann Intern Med 1974; 80(2):176–181Google Scholar
  19. 19.
    Larsen RA, Bozzette S, Mccutchan JA, Chiu J, Leal MA, Richman DD. Persistent Cryptococcus neoformans infection of the prostate after successful treatment of meningitis. Ann Intern Med 1989; 111(2):125–128PubMedGoogle Scholar
  20. 20.
    Perfect JR, Durack DT, Hamilton JD, Gallis HA. Failure of ketoconazole in cryptococcal meningitis. JAMA 1982; 247(24): 3349–3351PubMedCrossRefGoogle Scholar
  21. 21.
    Mitchell DH, Sorrell TC, Allworth AM et al. Cryptococcal disease of the CNS in immunocompetent hosts — influence of cryptococ-cal variety on clinical manifestations and outcome. Clin Infect Dis 1995; 20(3):611–616PubMedGoogle Scholar
  22. 22.
    Velez JD, Allendoerfer R, Luther M, Rinaldi MG, Graybill JR. Correlation of in vitro azole susceptibility with in-vivo response in a murine model of cryptococcal meningitis. J Infect Dis 1993; 168(2):508–510PubMedGoogle Scholar
  23. 23.
    Buchanan KL, Murphy JW. What makes Cryptococcus neoform-ans a pathogen? Emerg Infect Dis 1998; 4(1):71–83PubMedGoogle Scholar
  24. 24.
    Casadevall A, Rosas AL, Nosanchuk JD. Melanin and virulence in Cryptococcus neoformans. Curr Opin Microbiol 2000; 3(4):354–358PubMedCrossRefGoogle Scholar
  25. 25.
    van Duin D, Casadevall A, Nosanchuk JD. Melanization of Cryptococcus neoformans and Histoplasma capsulatum reduces their susceptibilities to amphotericin B and caspofungin. Antimicrob Agents Chemother 2002; 46(11):3394–3400PubMedCrossRefGoogle Scholar
  26. 26.
    Odom A, Muir S, Lim E, Toffaletti DL, Perfect J, Heitman J. Calcineurin is required for virulence of Cryptococcus neoformans. EMBO J 1997; 16(10):2576–2589PubMedCrossRefGoogle Scholar
  27. 27.
    Aller AI, Martin-Mazuelos E, Lozano F et al. Correlation of flu-conazole MICs with clinical outcome in cryptococcal infection. Antimicrob Agents Chemother 2000; 44(6):1544–1548PubMedCrossRefGoogle Scholar
  28. 28.
    Menichetti F, Fiorio M, Tosti A et al. High-dose fluconazole therapy for cryptococcal meningitis in patients with AIDS. Clin Infect Dis 1996; 22(5):838–840PubMedGoogle Scholar
  29. 29.
    Witt MD, Lewis RJ, Larsen RA et al. Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing. Clin Infect Dis 1996; 22(2):322–328PubMedGoogle Scholar
  30. 30.
    Barchiesi F, Colombo AL, Mcgough DA, Rinaldi MG. Comparative-study of broth macrodilution and microdilution techniques for in-vitro antifungal susceptibility testing of yeasts by using the National-Committee-For-Clinical-Laboratory-Standards Proposed Standard. J Clin Microbiol 1994; 32(10):2494–2500PubMedGoogle Scholar
  31. 31.
    Lozano-Chiu M, Paetznick VL, Ghannoum MA, Rex JH. Detection of resistance to amphotericin B among Cryptococcus neoformans clinical isolates: performances of three different media assessed by using E-test and National Committee for Clinical Laboratory Standards M27-A methodologies. J Clin Microbiol 1998; 36(10):2817–2822PubMedGoogle Scholar
  32. 32.
    Pfaller MA, Messer SA, Boyken L et al. Evaluation of the NCCLS M44-P disk diffusion method for determining susceptibilities of 276 clinical isolates of Cryptococcus neoformans to fluconazole. J Clin Microbiol 2004; 42(1):380–383PubMedCrossRefGoogle Scholar
  33. 33.
    Georgopapadakou NH, Walsh TJ. Antifungal agents: chemothera-peutic targets and immunologic strategies. [Review] [300 refs]. Antimicrob Agents Chemother 1996; 40(2):279–291PubMedGoogle Scholar
  34. 34.
    Aller AI, Martin-Mazuelos E, Gutierrez MJ, Bernal S, Chavez M, Recio FJ. Comparison of the Etest and microdilution method for antifungal susceptibility testing of Cryptococcus neoformans to four antifungal agents. J Antimicrob Chemother 2000; 46(6):997–1000PubMedCrossRefGoogle Scholar
  35. 35.
    Maxwell MJ, Messer SA, Hollis RJ, Diekema DJ, Pfaller MA. Evaluation of Etest method for determining voricona-zole and amphotericin B MICs for 162 clinical isolates of Cryptococcus neoformans. Journal of Clinical Microbiology 2003; 41(1):97–99PubMedCrossRefGoogle Scholar
  36. 36.
    Ghannoum MA, Ibrahim AS, Fu Y, Shafiq MC, Edwards JE, Criddle RS. Susceptibility testing of Cryptococcus neoformans — a micro-dilution technique. J Clin Microbiol 1992; 30(11):2881–2886PubMedGoogle Scholar
  37. 37.
    EspinelIngroff A, Kish CW, Kerkering TM et al. Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests. J Clin Microbiol 1992; 30(12):3138–3145Google Scholar
  38. 38.
    Currie B, Sanati H, Ibrahim AS, Edwards JE, Jr, Casadevall A, Ghannoum MA. Sterol compositions and susceptibilities to ampho-tericin B of environmental Cryptococcus neoformans isolates are changed by murine passage. Antimicrob Agents Chemother 1995; 39(9):1934–1937PubMedGoogle Scholar
  39. 39.
    Joseph-Horne T, Hollomon D, Loeffler RS, Kelly SL. Cross-resistance to polyene and azole drugs in Cryptococcus neoformans. Antimicrob Agents Chemother 1995; 39(7):1526–1529PubMedGoogle Scholar
  40. 40.
    Joseph-Horne T, Loeffler RS, Hollomon DW, Kelly SL. Amphotericin B resistant isolates of Cryptococcus neoformans without alteration in sterol biosynthesis. J Med Vet Mycol 1996; 34(3):223–225PubMedCrossRefGoogle Scholar
  41. 41.
    Kelly SL, Lamb DC, Kelly DE et al. Resistance to fluconazole and cross-resistance to amphotericin B in Candida albicans from AIDS patients caused by defective sterol delta5,6-desaturation. FEBS Lett 1997; 400(1):80–82PubMedCrossRefGoogle Scholar
  42. 42.
    Powderly WG, Keath WJ, Sokol-Anderson M, et al. Amphotericin B-resistant Cryptococcus neoformans in a patient with AIDS. Infect Dis Clin Pract 1992; 1:314–316Google Scholar
  43. 43.
    Casadevall A, Spitzer ED, Webb D, Rinaldi MG. Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole. Antimicrob Agents Chemother 1993; 37(6):1383–1386PubMedGoogle Scholar
  44. 44.
    Brandt ME, Pfaller MA, Hajjeh RA et al. Trends in antifungal drug susceptibility of Cryptococcus neoformans Isolates in the United States: 1992 to 1994 and 1996 to 1998. Antimicrob Agents Chemother 2001; 45(11):3065–3069PubMedCrossRefGoogle Scholar
  45. 45.
    Davey KG, Johnson EM, Holmes AD, Szekely A, Warnock DW. In-vitro susceptibility of Cryptococcus neoformans isolates to fluconazole and itraconazole. J Antimicrob Chemother 1998; 42(2):217–220PubMedCrossRefGoogle Scholar
  46. 46.
    Yildiran ST, Fothergill AW, Sutton DA, Rinaldi MG. In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592). Mycoses 2002; 45(9–10):378–383PubMedCrossRefGoogle Scholar
  47. 47.
    Pfaller MA, Diekema DJ, Gibbs DL et al. Results from the ARTEMIS 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):1735–1745CrossRefGoogle Scholar
  48. 48.
    Mondon P, Petter R, Amalfitano G et al. Heteroresistance to fluco-nazole and voriconazole in Cryptococcus neoformans. Antimicrob Agents Chemother 1999; 43(8):1856–1861PubMedGoogle Scholar
  49. 49.
    Bicanic T, Harrison T, Niepieklo A, Dyakopu N, Meintjes G. Symptomatic relapse of HIV-associated cryptococcal meningitis after initial fluconazole monotherapy: the role of fluconazole resistance and immune reconstitution. Clin Infect Dis 2006; 43(8):1069–1073PubMedCrossRefGoogle Scholar
  50. 50.
    Alexander BD, Perfect JR. Antifungal resistance trends towards the year 2000 — implications for therapy and new approaches. Drugs 1997; 54(5):657–678PubMedCrossRefGoogle Scholar
  51. 51.
    Loeffler J, Stevens DA. Antifungal drug resistance. Clin Infect Dis 2003; 36:S31–S41PubMedCrossRefGoogle Scholar
  52. 52.
    Perfect JR, Cox GM. Drug resistance in Cryptococcus neoformans. Drug Resist Updat 1999; 2(4):259–269PubMedCrossRefGoogle Scholar
  53. 53.
    White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 1998; 11(2):382–402PubMedGoogle Scholar
  54. 54.
    Ghannoum MA, Spellberg BJ, Ibrahim AS et al. Sterol composition of Cryptococcus neoformans in the presence and absence of fluco-nazole. Antimicrob Agents Chemother 1994; 38(9):2029–2033PubMedGoogle Scholar
  55. 55.
    Balkis MM, Leidich SD, Mukherjee PK, Ghannoum MA. Mechanisms of fungal resistance: an overview. Drugs 2002; 62(7):1025–1040PubMedCrossRefGoogle Scholar
  56. 56.
    Whelan WL. The genetic basis of resistance to 5-fluorocytosine in Candida species and Cryptococcus neoformans. Crit Rev Microbiol 1987; 15(1):45–56PubMedCrossRefGoogle Scholar
  57. 57.
    Perfect JR, Durack DT, Gallis HA. Cryptococcemia. Medicine 1983; 62(2):98–109PubMedCrossRefGoogle Scholar
  58. 58.
    Perfect JR, Cox GM. Drug resistance in Cryptococcus neoformans. Drug Resist Updat 1999; 2(4):259–269PubMedCrossRefGoogle Scholar
  59. 59.
    Hospenthal DR, Bennett JE. Flucytosine monotherapy for crypto-coccosis. Clin Infect Dis 1998; 27(2):260–264PubMedCrossRefGoogle Scholar
  60. 60.
    Bennett JE, Dismukes WE, Duma RJ et al. Comparison of ampho-tericin-B alone and combined with flucytosine in the treatment of cryptococcal meningitis. N Engl J Med 1979; 301(3):126–131PubMedGoogle Scholar
  61. 61.
    Saag MS, Graybill RJ, Larsen RA et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis 2000; 30(4):710–718PubMedCrossRefGoogle Scholar
  62. 62.
    Yildiran ST, Saracli MA, Fothergill AW, Rinaldi MG. In vitro susceptibility of environmental Cryptococcus neoformans variety neoformans isolates from Turkey to six antifungal agents, including SCH56592 and voriconazole. Eur J Clin Microbiol Infect Dis 2000; 19(4):317–319PubMedCrossRefGoogle Scholar
  63. 63.
    Venkateswarlu K, Taylor M, Manning NJ, Rinaldi MG, Kelly SL. Fluconazole tolerance in clinical isolates of Cryptococcus neofor-mans. Antimicrob Agents Chemother 1997; 41(4):748–751PubMedGoogle Scholar
  64. 64.
    Lamb DC, Corran A, Baldwin BC, Kwon-Chung J, Kelly SL. Resistant P45051A1 activity in azole antifungal tolerant Cryptococcus neoformans from AIDS patients. FEBS Lett 1995; 368(2):326–330PubMedCrossRefGoogle Scholar
  65. 65.
    Mellado E, Rodero L, Rodriquez C, et al. G484S amino acid substitution of 14-alpha lanosterol demethylase (ERG11) related to fluconazole resistance in recurrent Cryptococcus neoformans clinical isolate. 43rd ICAAC, 443, Chicago, IL, 2003Google Scholar
  66. 66.
    Posteraro B, Sanguinetti M, Sanglard D et al. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Mol Microbiol 2003; 47(2): 357–371PubMedCrossRefGoogle Scholar
  67. 67.
    Thornewell SJ, Peery RB, Skatrud PL. Cloning and characterization of CneMDR1: a Cryptococcus neoformans gene encoding a protein related to multidrug resistance proteins. Gene 1997; 201(1–2):21–29PubMedCrossRefGoogle Scholar
  68. 68.
    Xu J, Onyewu C, Yoell HJ, Ali RY, Vilgalys RJ, Mitchell TG. Dynamic and heterogeneous mutations to fluconazole resistance in Cryptococcus neoformans. Antimicrob Agents Chemother 2001; 45(2):420–427PubMedCrossRefGoogle Scholar
  69. 69.
    Yamazumi T, Pfaller MA, Messer SA et al. Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans. J Clin Microbiol 2003; 41(1):267–272PubMedCrossRefGoogle Scholar
  70. 70.
    Anaissie. EJ, McGinnis MR, Pfaller MA. Clinical Mycology. Philadelphia: 2003Google Scholar
  71. 71.
    Denning DW. Echinocandins: a new class of antifungal. [Review] [17 refs]. J Antimicrob Chemother 2002; 49(6):889–891PubMedCrossRefGoogle Scholar
  72. 72.
    Feldmesser M, Kress Y, Mednick A, Casadevall A. The effect of the echinocandin analogue caspofungin on cell wall glu-can synthesis by Cryptococcus neoformans. J Infect Dis 2000; 182(6):1791–1795PubMedCrossRefGoogle Scholar
  73. 73.
    Mazur P, Morin N, Baginsky W et al. Differential expression and function of two homologous subunits of yeast 1,3-beta-d-glucan synthase. Mol Cell Biol 1995; 15(10):5671–5681PubMedGoogle Scholar
  74. 74.
    Mio T, Adachi-Shimizu M, Tachibana Y et al. Cloning of the Candida albicans homolog of Saccharomyces cerevisiae GSC1/ FKS1 and its involvement in beta-1,3-glucan synthesis. J Bacteriol 1997; 179(13):4096–4105PubMedGoogle Scholar
  75. 75.
    Thompson JR, Douglas CM, Li W et al. A glucan synthase FKS1 homolog in Cryptococcus neoformans is single copy and encodes an essential function. J Bacteriol 1999; 181(2):444–453PubMedGoogle Scholar
  76. 76.
    Havlir DV, Dube MP, Mccutchan JA et al. Prophylaxis with weekly versus daily fluconazole for fungal infections in patients with AIDS. [see comment]. Clin Infect Dis 1998; 27(6):1369–1375PubMedCrossRefGoogle Scholar
  77. 77.
    McKinsey DS, Wheat LJ, Cloud GA et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study. National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis 1999; 28(5):1049–1056PubMedCrossRefGoogle Scholar
  78. 78.
    Kovacs JA, Masur H. Prophylaxis against opportunistic infections in patients with human immunodeficiency virus infection. N Engl J Med 2000; 342(19):1416–1429PubMedCrossRefGoogle Scholar
  79. 79.
    Kaplan JE, Masur H, Holmes KK et al. An overview of the 1999 US Public Health Service/Infectious Diseases Society of America guidelines for preventing opportunistic infections in human immunodeficiency virus-infected persons. Clin Infect Dis 2000; 30(Suppl 1):S15–S28PubMedCrossRefGoogle Scholar
  80. 80.
    Devi SJ, Schneerson R, Egan W et al. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity. Infect Immun 1991; 59(10):3700–3707PubMedGoogle Scholar
  81. 81.
    Devi SJ. Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. [erratum appears in Vaccine 1996 Sep;14(13):1298]. [Review] [29 refs]. Vaccine 1996; 14(9):841–844PubMedCrossRefGoogle Scholar
  82. 82.
    Deepe GS, Jr Prospects for the development of fungal vaccines. [Review] [114 refs]. Clin Microbiol Rev 1997; 10(4):585–596PubMedGoogle Scholar
  83. 83.
    Brummer E, Nassar F, Stevens DA. Effect of macrophage colony-stimulating factor on anticryptococcal activity of bronchoalveolar macrophages: synergy with fluconazole for killing. Antimicrob Agents Chemother 1994; 38(9):2158–2161PubMedGoogle Scholar
  84. 84.
    Chiller T, Farrokhshad K, Brummer E, Stevens DA. Effect of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on polymorphonuclear neutrophils, mono-cytes or monocyte-derived macrophages combined with voriconazole against Cryptococcus neoformans. Med Mycol 2002; 40(1):21–26PubMedCrossRefGoogle Scholar
  85. 85.
    Tascini C, Vecchiarelli A, Preziosi R, Francisci D, Bistoni F, Baldelli F. Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anti-cryptococcal activity of monocytes from AIDS patients. AIDS 1999; 13(1):49–55PubMedCrossRefGoogle Scholar
  86. 86.
    Herrmann JL, Dubois N, Fourgeaud M, Basset D, Lagrange PH. Synergic inhibitory activity of amphotericin-B and gamma inter-feron against intracellular Cryptococcus neoformans in murine macrophages. J Antimicrob Chemother 1994; 34(6):1051–1058PubMedCrossRefGoogle Scholar
  87. 87.
    Pietrella D, Kozel TR, Monari C, Bistoni F, Vecchiarelli A. Interleukin-12 counterbalances the deleterious effect of human immunodeficiency virus type 1 envelope glycoprotein gp120 on the immune response to Cryptococcus neoformans. J Infect Dis 2001; 183(1):51–58PubMedCrossRefGoogle Scholar
  88. 88.
    Zhang T, Kawakami K, Qureshi MH, Okamura H, Kurimoto M, Saito A. Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudate cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells. Infect Immun 1997; 65(9):3594–3599PubMedGoogle Scholar
  89. 89.
    Levitz SM. Activation of human peripheral blood mononuclear cells by interleukin-2 and granulocyte-macrophage colony- stimulating factor to inhibit Cryptococcus neoformans. Infect Immun 1991; 59(10):3393–3397PubMedGoogle Scholar
  90. 90.
    Pappas PG, Bustamante B, Ticona E, et al. Adjuvant interferon gamma for the treatment of Cryptococcal meningitis: a randomized double blind pilot trial. 41st ICAAC. 2001Google Scholar
  91. 91.
    Casadevall A. Antibody-based therapies for emerging infectious diseases. [Review] [68 refs]. Emerg Infect Dis 1996; 2(3):200–208PubMedCrossRefGoogle Scholar
  92. 92.
    Feldmesser M, Mukherjee J, Casadevall A. Combination of 5-flu-cytosine and capsule-binding monoclonal antibody in the treatment of murine Cryptococcus neoformans infections and in vitro. J Antimicrob Chemother 1996; 37(3):617–622PubMedCrossRefGoogle Scholar
  93. 93.
    Mukherjee J, Zuckier LS, Scharff MD, Casadevall A. Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphoter-icin B. Antimicrob Agents Chemother 1994; 38(3):580–587PubMedGoogle Scholar
  94. 94.
    Mukherjee J, Feldmesser M, Scharff MD, Casadevall A. Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy. Antimicrob Agents Chemother 1995; 39(7):1398–1405PubMedGoogle Scholar
  95. 95.
    Rosas AL, Nosanchuk JD, Casadevall A. Passive immunization with melanin-binding monoclonal antibodies prolongs survival of mice with lethal Cryptococcus neoformans infection. Infect Immun 2001; 69(5):3410–3412PubMedCrossRefGoogle Scholar
  96. 96.
    van der Horst CM, Saag MS, Cloud GA et al. Treatment of crypto-coccal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group [see comment]. N Engl J Med 1997; 337(1):15–21Google Scholar
  97. 97.
    Coker RJ, Viviani M, Gazzard BG et al. Treatment of cryptococ-cosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS. AIDS 1993; 7(6):829–835PubMedCrossRefGoogle Scholar
  98. 98.
    Leenders AC, Reiss P, Portegies P et al. Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis. AIDS 1997; 11(12):1463–1471PubMedCrossRefGoogle Scholar
  99. 99.
    Duswald KH, Penk A, Pittrow L. High-dose therapy with fluco-nazole > or = 800 mg day-1. Mycoses 1997; 40(7–8):267–277PubMedCrossRefGoogle Scholar
  100. 100.
    Pfaller MA, Zhang J, Messer SA et al. In vitro activities of voriconazole, fluconazole, and itraconazole against 566 clinical isolates of Cryptococcus neoformans from the United States and Africa. Antimicrob Agents Chemother 1999; 43(1):169–171PubMedGoogle Scholar
  101. 101.
    Perfect JR, Marr KA, Walsh TJ et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 2003; 36(9):1122–1131PubMedCrossRefGoogle Scholar
  102. 102.
    Nguyen MH, Yu CY. In vitro comparative efficacy of vorico-nazole and itraconazole against fluconazole-susceptible and -resistant Cryptococcus neoformans isolates. Antimicrob Agents Chemother 1998; 42(2):471–472PubMedGoogle Scholar
  103. 103.
    Yamazumi T, Pfaller MA, Messer SA, Houston A, Hollis RJ, Jones RN. In vitro activities of ravuconazole (BMS-207147) against 541 clinical isolates of Cryptococcus neoformans. Antimicrob Agents Chemother 2000; 44(10):2883–2886PubMedCrossRefGoogle Scholar
  104. 104.
    Pfaller MA, Messer SA, Hollis RJ, Jones RN. In vitro activities of posaconazole (Sch 56592) compared with those of itraconazole and fluconazole against 3,685 clinical isolates of Candida spp. and Cryptococcus neoformans. Antimicrob Agents Chemother 2001; 45(10):2862–2864PubMedCrossRefGoogle Scholar
  105. 105.
    Brouwer AE, Rajanuwong A, Chierakul W. Combination anti-fungal therapies for HIV-associated cryptococcal meningitis: feasibility and powers of quantitative CSF cultures to determine fungicidal activity. Lancet (in press)Google Scholar
  106. 106.
    Mayanja-Kizza H, Oishi K, Mitarai S et al. Combination therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandan patients with AIDS. [see comment]. Clin Infect Dis 1998; 26(6):1362–1366PubMedCrossRefGoogle Scholar
  107. 107.
    Larsen RA, Bozzette SA, Jones BE et al. Fluconazole combined with flucytosine for treatment of cryptococcal meningitis in patients with AIDS. Clin Infect Dis 1994; 19(4):741–745PubMedGoogle Scholar
  108. 108.
    Rex JH, Pappas PG, Karchmer AW et al. A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candi-demia and its consequences in nonneutropenic subjects.[see comment]. Clin Infect Dis 2003; 36(10):1221–1228PubMedCrossRefGoogle Scholar
  109. 109.
    Fujita NK, Edwards JE, Jr. Combined in vitro effect of ampho-tericin B and rifampin on Cryptococcus neoformans. Antimicrob Agents Chemother 1981; 19(1):196–198PubMedGoogle Scholar
  110. 110.
    Franzot SP, Casadevall A. Pneumocandin L-743,872 enhances the activities of amphotericin B and fluconazole against Cryptococcus neoformans in vitro. Antimicrob Agents Chemother 1997; 41(2):331–336PubMedGoogle Scholar
  111. 111.
    Barchiesi F, Schimizzi AM, Najvar LK et al. Interactions of posaconazole and flucytosine against Cryptococcus neoformans. Antimicrob Agents Chemother 2001; 45(5):1355–1359PubMedCrossRefGoogle Scholar
  112. 112.
    Neely MN, Ghannoum MA. The exciting future of antifungal therapy. [Review] [208 refs]. Eur J Clin Microbiol Infect Dis 2000; 19(12):897–914PubMedCrossRefGoogle Scholar
  113. 113.
    Fujita NK, Reynard M, Sapico FL, Guze LB, Edwards JE, Jr. Cryptococcal intracerebral mass lesions: the role of computed tomography and nonsurgical management. Ann Intern Med 1981; 94(3):382–388PubMedGoogle Scholar
  114. 114.
    Hammerman KJ, Powell KE, Christianson CS et al. Pulmonary cryptococcosis: clinical forms and treatment. A Center for Disease Control cooperative mycoses study. Am Rev Respir Dis 1973; 108(5):1116–1123PubMedGoogle Scholar
  115. 115.
    Cruz MC, Edlind T. beta-Tubulin genes and the basis for benz-imidazole sensitivity of the opportunistic fungus Cryptococcus neoformans. Microbiology 1997; 143(Pt 6):2003–2008PubMedCrossRefGoogle Scholar
  116. 116.
    Del Poeta M, Bixel AS, Barchiesi F et al. In-vitro activity of dica-tionic aromatic compounds and fluconazole against Cryptococcus neoformans and Candida spp. J Antimicrob Chemother 1999; 44(2):223–228PubMedCrossRefGoogle Scholar
  117. 117.
    Cruz MC, Cavallo LM, Gorlach JM et al. Rapamycin antifungal action is mediated via conserved complexes with FKBP12 and TOR kinase homologs in Cryptococcus neoformans. Mol Cell Biol 1999; 19(6):4101–4112PubMedGoogle Scholar
  118. 118.
    Cruz MC, Del Poeta M, Wang P et al. Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin. Antimicrob Agents Chemother 2000; 44(1):143–149PubMedCrossRefGoogle Scholar
  119. 119.
    Cruz MC, Goldstein AL, Blankenship J et al. Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR. Antimicrob Agents Chemother 2001; 45(11): 3162–3170PubMedCrossRefGoogle Scholar
  120. 120.
    Odom A, Del Poeta M, Perfect J, Heitman J. The immu-nosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein. Antimicrob Agents Chemother 1997; 41(1):156–161PubMedGoogle Scholar
  121. 121.
    Husain S, John G, Singh N. Changing spectrum of C. neofor-mans infection in organ transplant recipients in the era/area of calcineurin-inhibitor based immunosuppression (tacrolimus and cyclosporine, CsA). 42nd ICAAC, 392, 2002Google Scholar
  122. 122.
    Cardenas ME, Sanfridson A, Cutler NS, Heitman J. Signal-transduction cascades as targets for therapeutic intervention by natural products. [Review] [71 refs]. Trends Biotechnol 1998; 16(10):427–433PubMedCrossRefGoogle Scholar
  123. 123.
    Drose S, Altendorf K. Bafilomycins and concanamycins as inhibitors of V-ATPases and P-ATPases. [Review] [69 refs]. J Exp Biol 1997; 200(Pt 1):1–8PubMedGoogle Scholar
  124. 124.
    Hunke S, Dose S, Schneider E. Vanadate and bafilomycin A1 are potent inhibitors of the ATPase activity of the reconstituted bac- terial ATP-binding cassette transporter for maltose (MalFGK2). Biochem Biophys Res Commun 1995; 216(2):589–594PubMedCrossRefGoogle Scholar
  125. 125.
    Manavathu EK, Dimmock JR, Vashishtha SC, Chandrasekar PH. Inhibition of H(+)-ATPase-mediated proton pumping in Cryptococcus neoformans by a novel conjugated styryl ketone. J Antimicrob Chemother 2001; 47(4):491–494PubMedCrossRefGoogle Scholar
  126. 126.
    Garrett-Engele P, Moilanen B, Cyert MS. Calcineurin, the Ca2+/calmodulin-dependent protein phosphatase, is essential in yeast mutants with cell integrity defects and in mutants that lack a functional vacuolar H(+)-ATPase. Mol Cell Biol 1995; 15(8):4103–4114PubMedGoogle Scholar
  127. 127.
    Del Poeta M, Cruz MC, Cardenas ME, Perfect JR, Heitman J. Synergistic antifungal activities of bafilomycin A(1), fluco-nazole, and the pneumocandin MK-0991/caspofungin acetate (L-743,873) with calcineurin inhibitors FK506 and L-685,818 against Cryptococcus neoformans. Antimicrob Agents Chemother 2000; 44(3):739–746PubMedCrossRefGoogle Scholar
  128. 128.
    Dominguez JM, Kelly VA, Kinsman OS, Marriott MS, Gomez de las HF, Martin JJ. Sordarins: A new class of antifungals with selective inhibition of the protein synthesis elongation cycle in yeasts. Antimicrob Agents Chemother 1998; 42(9):2274–2278PubMedGoogle Scholar
  129. 129.
    Chamberlin S, Blais J, Cotter DP, et al. Impact of MC-510,027, a fungal efflux pump inhibitor, on the susceptibility of clinical isolates of Candida spp. to antifungal agents. 39th ICAAC, 1999Google Scholar
  130. 130.
    Harrison TS, Griffin GE, Levitz SM. Conditional lethality of the diprotic weak bases chloroquine and quinacrine against Cryptococcus neoformans. J Infect Dis 2000; 182(1):283–289PubMedCrossRefGoogle Scholar
  131. 131.
    Mazzolla R, Barluzzi R, Brozzetti A et al. Enhanced resistance to Cryptococcus neoformans infection induced by chloroquine in a murine model of meningoencephalitis. Antimicrob Agents Chemother 1997; 41(4):802–807PubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Kimberly E. Hanson
    • 1
  • Barbara D. Alexander
    • 1
  • John Perfect
    • 1
  1. 1.Division Infections DiseasesDuke University Medical CenterDurhamUSA

Personalised recommendations