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Antifungal Resistance: Aspergillus

  • P. H. Chandrasekar
  • Elias K. Manavathu
Part of the Infectious Disease book series (ID)

Despite the availability of potent antifungal agents, systemic fungal infections continue to cause signifi cant morbidity and mortality. While candida-related deaths have declined since the late 1980s, those due to aspergillosis remain high. Fifty to ninety percent of patients with invasive aspergillosis (IA) die despite treatment (1–3). Susceptible hosts, particularly cancer patients and transplant recipients, are profoundly immunocompromised with neutropenia and/or impaired monocyte/macrophage dysfunction; there is universal agreement that the outcome of IA is largely dictated by the host immune status (4–6). Regardless of the antifungal drug(s) employed, the poor outcome or failure of antifungal therapy is generally attributed to compromised host defenses and in most cases, not considered to be due to drug resistant fungi. Also, failure of antifungal drugs may be due to inappropriate dose, fungistatic activity, high protein binding, poor absorption/ distribution and metabolism or drug interactions. Until recently, drug resistance in aspergillus was not adequately examined.

Keywords

Invasive Aspergillosis Antimicrob Agent Aspergillus Fumigatus Antifungal Drug Liposomal Amphotericin 
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.

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References

  1. 1.
    McNeil MM, Nash SL, Hajjeyh RA, Phelan MA, Conn LA, Pkikaytis BD, et al. Trends in mortality due to invasive mycotic diseases in the United States. 1980–1997. Clin Infect Dis 2001; 33:641–647.PubMedCrossRefGoogle Scholar
  2. 2.
    Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001; 232:1319–1324.CrossRefGoogle Scholar
  3. 3.
    Marr KA, Carter RA, Crippa F, Wald A, Corey L. Epidemiology and outcome of mould infections in hematopeietic stem cell transplant recipients. Clin Infect Dis 2002; 34:909–917.PubMedCrossRefGoogle Scholar
  4. 4.
    Denning DW, Invasive aspergillosis in immunocompromised patients. Curr Opin Infect Dis 1994; 7:456–462.CrossRefGoogle Scholar
  5. 5.
    Schaffner A, Douglas H, Braude A. Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J Clin Invest 1982; 69:617–631.PubMedCrossRefGoogle Scholar
  6. 6.
    Schneemann M, Schaffner A. Host defense mechanism in Aspergillus fumigatus infections. Contrib Microbiol 1999; 2:57–68.PubMedCrossRefGoogle Scholar
  7. 7.
    National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: approved standard (NCCLS document M38-A). Wayne, PA: National Committee for Clinical Laboratory Standards, 2002.Google Scholar
  8. 8.
    Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002; 292:107–113.PubMedCrossRefGoogle Scholar
  9. 9.
    Youngchim S, Morris-Jones R, Hay RJ, Hamilton AJ. Production of melanin by Aspergillus fumigatus. J Med Microbiol 2004; 53:175–181.PubMedCrossRefGoogle Scholar
  10. 10.
    Langfelder K, Streibel M, Jahn B, Haase G, Brakhage AA. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol 2003; 38:143–158.PubMedCrossRefGoogle Scholar
  11. 11.
    Sugar AM. The polyene macrolide antifungal drugs. In P.K. Peterson and J. Verhoef (eds.), Antimicrobial Agents, vol. 1, pp 229–244. Elsevier, Amsterdam, the Netherlands, 1986.Google Scholar
  12. 12.
    Kerridge D. The plasma membrane of Candida albicans and its role in the action of antifungal drugs. In G. W. Gooday, D. Lloyd, and A.P.J. Trinci (eds.), The Eukaryotic Microbial Cell, p 103. Cambridge University Press, Cambridge, England, 1980.Google Scholar
  13. 13.
    Brajtburg J, Powderly WG, Kobayashi GS, Medoff G. Amphotericin B: current understanding of mechanisms of action. Antimicrob Agents Chemother 1990; 34:183–188.PubMedGoogle Scholar
  14. 14.
    Manavathu EK, Alangaden GJ, Chandrasekar PH. In-vitro isolation and antifungal susceptibility of amphotericin B-resistant mutants of Aspergillus fumigatus. J Antimicrob Chemother 1998; 41:615–619.PubMedCrossRefGoogle Scholar
  15. 15.
    Verweij PE, Oakley KL, Morrissey J, Morrissey G, Denning DW. Efficacy of LY303366 against amphotericin B-susceptible and -resistant Aspergillus fumigatus in a murine model of invasive aspergillosis. Antimicrob Agents Chemother 1998; 42:873–878.PubMedGoogle Scholar
  16. 16.
    Odds FC, Gerven FV, Espinel-Ingroff A, Bartlett MS, et al. Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models. Antimicrob Agents Chemother 1998; 42:282–288.PubMedGoogle Scholar
  17. 17.
    Seo K, Akiyoshi H, Ohnishi Y. Alteration of cell wall composition leads to amphotericin B resistance in Aspergillus flavus. Microbiol Immunol 1999; 43:1017–1025.PubMedGoogle Scholar
  18. 18.
    Walsh TJ, Petraitis V, Petraitiene R, Field-Ridley A, 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; 188:305–319.PubMedCrossRefGoogle Scholar
  19. 19.
    Manavathu EK, Cutright JL, Chandrasekar PH. In vivo resistance of a laboratory-selected Aspergillus fumigatus isolate to amphotericin B. Antimcrob Agents Chemother 2005; 49:428–430.CrossRefGoogle Scholar
  20. 20.
    Balajee SA, Gribskov JL, Hanley E, Nickle D, Marr KA. Aspergillus lentulus sp. nov. a new sibling species of A. fumigatus. Eukaryot Cell 2005; 4:625–632.PubMedCrossRefGoogle Scholar
  21. 21.
    Balajee SA, Nickle D, Varga J, Marr KA. Molecular studies reveal frequent misidentification of Aspergillus fumigatus by morphotyping. Eukaryot Cell 2006; 5:1705–1712.PubMedCrossRefGoogle Scholar
  22. 22.
    Vanden Bossche H, Lauwers W, Willemsens G, Marichal P, et al. Molecular basis for the antimycotic and antibacterial activity of N-substituted immidazoles and triazoles: the inhibition of isoprenoid biosynthesis. Pest Sci 1984; 15:188–198.CrossRefGoogle Scholar
  23. 23.
    Yoshida Y, Ayoma Y. Interaction of azole antifungal agents with cytochrome P45014DM purified from Saccharomyces cerevisiae microsomes. Biochem Pharmacol 1987; 36:229–235.PubMedCrossRefGoogle Scholar
  24. 24.
    Tuck SF, Aoyama Y, Yoshida Y, Ortiz de Montellano PR. Active site topology of Saccharomyces cerevisiae lanosterol 14α-demethylase (CYP51) and its G301Δ mutant (cytochrome P4503G1). J Biol Chem 1992; 267:13175–13179.PubMedGoogle Scholar
  25. 25.
    Vanden Bossche H. Biochemical targets for antifungal azole derivatives: hypothesis on the mode of action. In M. R McGinnis (ed.), Current Topics in Medical Mycology, pp 313–351, Springer, New York, 1985.Google Scholar
  26. 26.
    Sabo JA, Abdel-Rahman SM. Voriconazole: a new triazole antifungal. Ann Pharmacother 2000; 34:1032–1043.PubMedCrossRefGoogle Scholar
  27. 27.
    Manavathu EK, Baskaran I, Alangaden GJ, Chandrasekar PH. Molecular characterization of the P450-dependent lanosterol demethylase gene from clinical isolates of Aspergillus fumigatus. In Abstracts of the 101st General Meeting of the American Society for Microbiology, May 20–24, 2001, Orlando, FL. Abstract F-20.Google Scholar
  28. 28.
    Mellado E, Diaz-Guerra TM, Cuenca-Estrella M, Rodriguez-Tudela JL. Identification of two different 14α-sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J Clin Microbiol 2001; 39:2431–2438.PubMedCrossRefGoogle Scholar
  29. 29.
    Osherov N, Kontoyannis DP, Romans A, May GS. Resistance to itraconazole in Aspergillus nidulans and Aspergillus fumigatus is conferred by extra copies of the A. nidulans P-450 14α-demethylase gene, pdmA. J Antimicrob Chemother 2001; 48:75–81.PubMedCrossRefGoogle Scholar
  30. 30.
    Denning DW, Venkateswarlu K, Oakley KL, Anderson MJ, et al. Itraconazole resistance in Aspergillus fumigatus, Antimicrob Agents Chemother 1997; 41:1364–1368.PubMedGoogle Scholar
  31. 31.
    Manavathu EK, Abraham OC, Chandrasekar PH. Isolation and in vitro susceptibility of voriconazole-resistant laboratory isolates of Aspergillus fumigatus. Clin Microbiol Infect 2001; 7:130–137.PubMedCrossRefGoogle Scholar
  32. 32.
    Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela JL. A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 2003; 47:1120–1124.PubMedCrossRefGoogle Scholar
  33. 33.
    Nascimento AM, Goldman GH, Park S, Marras SAE, et al. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole.Antimicrob Agents Chemother 2003; 47:1719–1726.PubMedCrossRefGoogle Scholar
  34. 34.
    Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela JL. Substitutions at methionine 220 in the 14α-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob Agents Chemother 2004; 48:2747–2750.PubMedCrossRefGoogle Scholar
  35. 35.
    da Silva Ferreira ME, Capellaro JL, dos Reis Marques E, Malavazi I, Perlin D, Park S, Anderson JB, Colombo AL, Arthington-Skaggs BA, Goldman MH, Goldman GH. In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob Agents Chemother 2004; 48:4405–4413.PubMedCrossRefGoogle Scholar
  36. 36.
    Chen J, Li H, Li R, Bu D, Wan Z. Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J Antimicrob Chemother 2005; 55:31–37.PubMedCrossRefGoogle Scholar
  37. 37.
    Dannaoui ED, Garcia-Hemoso D, Naccache JM, Meneau I, Sanglard D, Bouges-Michel C, Valeyre D, Lortholary O. Use of voriconazole in a patient with aspergilloma caused by an itraco-nazole-resistant strain of Aspergillus fumigatus. J Med Microbiol 2006; 55:1457–1459.PubMedCrossRefGoogle Scholar
  38. 38.
    Howard SJ, Webster I, Moore CB, Gardiner RE, Park S, Perlin DS, Denning DW. Multiazole resistance in Aspergillus fumigatus. Int J Antimicrob Agents 2006; 28:450–453.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaya AD, Kiraza N. In vitro susceptibilities of Aspergillus spp. Causing otomycosis to amphotericin B, voriconazole, and itraconazole. Mycoses 2007; 50:447–450.PubMedCrossRefGoogle Scholar
  40. 40.
    Mellado E, Garcia-Effron G, Alcázar-Fuoli L, Melchers WJG, Verweij PE, Cuenca-Estrella M, Rodrïguez-Tudela JL. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 2007; 51:1897–1904.PubMedCrossRefGoogle Scholar
  41. 41.
    Manavathu EK, Espinel-Ingroff A, Alangaden GJ, Chandrasekar PH. Molecular studies on voriconazole-resistance in a clinical isolate of Aspergillus fumigatus. 43rd ICAAC 2003, Abstract M-392.Google Scholar
  42. 42.
    Mann PA, Parmegiani RM, Wei SO, Mendrick CA, et al. Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14α-demethylase. Antimicrob Agents Chemother 2003; 47:577–581.PubMedCrossRefGoogle Scholar
  43. 43.
    Xiao L, Madison V, Chau AS, Loebenberg D, et al. Three-dimensional models of wild-type and mutated forms of cytochrome P450 14α-sterol demethylases from Aspergillus fumigatus and Candida albicans provide insights into posaconazole binding. Antimicrob Agents Chemother 2004; 48:568–574.PubMedCrossRefGoogle Scholar
  44. 44.
    Boscott PE, Grant GH. Modeling of cytochrome P450 14α-demethylase (Candida albicans) from P450cam. J Mol Graph 1994; 12:185–193.PubMedCrossRefGoogle Scholar
  45. 45.
    Podust LM, Stojan J, Poulos TL, Watermann MR. Substrate recognition sites in 14α-sterol demethylase from comparative analysis of amino acid sequences and X-ray structure of Mycobacterium tuberculosis CYP51. J Inorg Biochem 2001; 87:227–235.PubMedCrossRefGoogle Scholar
  46. 46.
    White TC. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob Agents Chemother 1997; 41:1482–1487.PubMedGoogle Scholar
  47. 47.
    Sanglard D, Kuchler K, Ischer F, Pagani JL, et al. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother 1995; 39;2378–2386.PubMedGoogle Scholar
  48. 48.
    Prasad R, Wergifosse P, Goffeau A, Balzi E. Molecular cloning and characterization of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals. Curr Genet 1995; 27:320–329.PubMedCrossRefGoogle Scholar
  49. 49.
    Parkinson T, Falconer DJ, Hitchcock CA. Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. Antimicrob Agents Chemother 1995; 39;1696–1699.PubMedGoogle Scholar
  50. 50.
    Venkateswarlu K, Denning DW, Manning NJ, Kelly SL. Resistance to fluconazole in Candida albicans from AIDS patients correlated with reduced intracellular accumulation of drug. FEMS Microbiol Lett 1995; 131:337–341.PubMedCrossRefGoogle Scholar
  51. 51.
    Albertson GD, Niimi M, Cannon RD, Jenkinson HF. Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrob Agents Chemother 1996; 40:2835–2841.PubMedGoogle Scholar
  52. 52.
    Slaven JW, Anderson MJ, Sanglard D, Dixson GK, et al. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in itraconazole resistant clinical isolate. Fungal Genet Biol 2002; 36:199–206.PubMedCrossRefGoogle Scholar
  53. 53.
    Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 1999; 12:310–350.PubMedGoogle Scholar
  54. 54.
    Manavathu EK, Vasquez JA, Chandrasekar PH. Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent. Int J Antimicrob Agents 1999; 12:213–219.PubMedCrossRefGoogle Scholar
  55. 55.
    Douglas CM, D'Ippolito JA, Shei GJ, Meinz M, et al. Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-β-d-glucan synthase inhibitors. Antimicrob Agents Chemother 1997; 41:2471–2479.PubMedGoogle Scholar
  56. 56.
    Gardiner RE, Souteropoulos P, Park S, Perlin DS. Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin. Med Mycol 2005; 43 Suppl 1:S299–S305.PubMedCrossRefGoogle Scholar
  57. 57.
    Rocha EMF, Garcia-Effron G, Park S, Perlin DS. A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob Agents Chemother 2007; 51:4174–4176.PubMedCrossRefGoogle Scholar
  58. 58.
    Petranyi G, Petraitiene R, Sarafandi AA, Kelaher AM, et al. Antifungal activity of the allylamine derivative terbinafine in vitro. Antimicrob Agents Chemother 1987; 31:1365–1368.PubMedGoogle Scholar
  59. 59.
    Ryder NS, Leiner I. Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species. Med Mycol 2001; 39:91–95.PubMedCrossRefGoogle Scholar
  60. 60.
    Ryder NS, Favre B. Antifungal activity and mechanism of action of terbinafine. Rev Contemp Pharmacother 1997; 8:275–287.Google Scholar
  61. 61.
    Mosquera J, Moore CB, Warn PA, Denning DW. In vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine against Aspergillus species. J Antimicrob Chemother 2002; 50:189–194.PubMedCrossRefGoogle Scholar
  62. 62.
    Liu W, May GS, Lionakis MS, Lewis RE, et al. Extra copies of the Aspergillus fumigatus squalene epoxidase gene confer resistance to terbinafine: genetic approach to studying gene dose-dependent resistance to antifungals in A. fumigatus. Antimicrob Agents Chemother 2004; 48:2490–2496.PubMedCrossRefGoogle Scholar
  63. 63.
    Graminha MAS, Rocha EMF, Prade RA, Martinez-Rossi NM. Terbinafine resistance mediated by salicylate 1-monooxygenase in Aspergillus nidulans. Antimicrob Agents Chemother 2004; 48:3530–3535.PubMedCrossRefGoogle Scholar
  64. 64.
    Rocha EMF, Gardiner RE, Park S, Martinez-Rossi NM, Perlin DS. A Phe389Leu substitution in ErgA confers terbinafine resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 2006; 50:2533–2536.PubMedCrossRefGoogle Scholar
  65. 65.
    Clemons K V, Stevens DA. The contribution of animal models of aspergillosis to understanding pathogenesis, therapy and virulence. Med Mycol 2005; 43: (Suppl 1):S101–S110.PubMedCrossRefGoogle Scholar
  66. 66.
    Van Etten EW, Stearne-Cullen LE, ten Kate M, Bakker-Woudenberg IA. Efficacy of liposomal amphotericin B with prolonged circulation in blood in treatment of severe pulmonary aspergillosis in leukopenic rats. Antimicrob Agents Chemother 2000; 44:540–545.CrossRefGoogle Scholar
  67. 67.
    Murphy M, Bernard EM, Ishimaru T, Armstrong D. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother 1997; 41:696–698.PubMedGoogle Scholar
  68. 68.
    Van Cutsem J, Janssen PJ. In vitro and in vivo models to study the activity of antifungals against Aspergillus. In H. Vanden Bossche, D.W.R. MacKenzie, and G. Cauwenbergh (eds.), Aspergillus and Aspergillosis, pp 215–227. Plenum, New York, N Y.Google Scholar
  69. 69.
    Chakrabarti A, Jatana M, Sharma SC. Rabbit as an animal model of paranasal sinus mycoses. J Med Vet Mycol 1997; 35:295–297.PubMedCrossRefGoogle Scholar
  70. 70.
    Sutton DA, Sanche SE, Revankar SG, Fothergill AQ, Rinaldi MG. In vitro amphotericin B resistance in clinical isolates of Aspergillus terreus, a head-to-head comparison of voriconazole. Clin Infect Dis 2004; 39:743–746.CrossRefGoogle Scholar
  71. 71.
    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; 51:913–919.PubMedCrossRefGoogle Scholar
  72. 72.
    Iwen PC, Rupp ME, Bishop MR, Rinaldi MG, Sutton DA, Tarantolo S, Hinrichs SH. Disseminated aspergillosis caused by Aspergillus ustus in a patient following allogeneic peripheral stem cell transplantation. J Clin Microbiol 1998; 36:3713–3717.PubMedGoogle Scholar
  73. 73.
    Pavie J, Lacroix C, Hermoso DG, Robin M, Ferry C, Bergeron A, Feuilhade M, Dromer F, Gluckman E, Molina J-M, Ribaud P. Breakthrough disseminated Aspergillus ustus infection in allogeneic hematopoietic stem cell transplant recipients receiving voriconazole or caspofungin prophylaxis. J Clin Microbiol 2005; 43:4902–4904.PubMedCrossRefGoogle Scholar
  74. 74.
    Imhof A, Balajee SA, Fredricks DN, Englund JA, Marr KA. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole. Clin Infect Dis 2004; 39:743–746.PubMedCrossRefGoogle Scholar
  75. 75.
    Iwen PC, Rupp ME, Langnas AN, Reed EC, Hinrichs SH. Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature. Clin Infect Dis 1998; 26:1092–1097.PubMedCrossRefGoogle Scholar
  76. 76.
    Steinbach WJ, Benjamin DK Jr., Kontoyiannis DP, Perfect FR, Lutsar I, Marr KA, et al. Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases. Clin Infect Dis 2004; 39:192–198.PubMedCrossRefGoogle Scholar
  77. 77.
    Lass-Florl C, Kofler G, Kropshofer G, et al. In vitro testing of susceptibility of amphotericin B is reliable predictor of clinical outcome in invasive aspergillosis. J Antimicrob Chemother 1998; 42:497–502.PubMedCrossRefGoogle Scholar
  78. 78.
    Frankenbusch K, Eifinger F, Kribs A, Rengelshauseu J, Roth B. Severe primary cutaneous aspergillosis refractory to amphotericin B and the successful treatment with systemic voriconazole in two premature infants with extremely low birth weight. J Perinatol 2006; 26:511–514.PubMedCrossRefGoogle Scholar
  79. 79.
    Lionakis MS, Lewis RE, Torres HA, Albert ND, Raad II, Kontoyiannis DP. Increased frequency of non-fumigatus Aspergillus species in amphotericin B- or triazole-pre-exposed cancer patients with positive cultures for aspergilli. Diagn Microbiol Infect Dis 2005; 52:15–20.PubMedCrossRefGoogle Scholar
  80. 80.
    Moosa M Y, Alangaden GJ, Manavathu EK, Chandrasekar PH. Resistance to amphotericin B does not emerge during treatment for invasive aspergillosis. J Antimicrob Chemother 2002; 49:209–213.PubMedCrossRefGoogle Scholar
  81. 81.
    Dannaoui E. Meletiadis J, Tortorano AM, et al. Susceptibility testing of sequential isolates of Aspergillus fumigatus recovered from treated patients. J Med Microbiol 2004; 53:129–134.PubMedCrossRefGoogle Scholar
  82. 82.
    Paterson PJ, Seaton S, Prentice HG, Kibbler CC. Treatment failure in invasive aspergillosis: susceptibility of deep tissue isolates following treatment with amphotericin B. J Antimicrob Chemother 2003; 52:873–876.PubMedCrossRefGoogle Scholar
  83. 83.
    Chrysssanthou E. In vitro susceptibility of respiratory isolates of Aspergillus species to itraconazole and amphotericin B acquired resistance to itraconazole. Scand J Infect Dis 1997; 29:509–512.CrossRefGoogle Scholar
  84. 84.
    Oakley KL, Morrissey G, Denning DW. Efficacy of SCH-56592 in a temporarily neutropenic murine model of invasive aspergillosis with an itraconazole-susceptible and an itraconazole-resistant isolate of Aspergillus fumigatus. Antimicrob Agents Chemother 1997; 41:1504–1507.PubMedGoogle Scholar
  85. 85.
    Dannaoui E, Borel E, Monier MR, Piens MA, et al. Acquired itraconazole resistance in Aspergillus fumigatus. J Antimicrob Chem 2001; 47:333–340.CrossRefGoogle Scholar
  86. 86.
    Verweij PE, TE Dorsthorst DTA, Rijs AJMM, et al. Nationwide survey of in vitro activities of itraconazole and voriconazole against clinical Aspergillus fumigatus isolates cultured between 1945 and 1998. J Clin Microb 2002; 47:2648–2650.CrossRefGoogle Scholar
  87. 87.
    Balajee SA, Weaver M, Imhof A, et al. Aspergillus fumigatus variant with decreased susceptibility to multiple antifungals. Antimicrob Agents Chemother 2004; 48:1197–1203.PubMedCrossRefGoogle Scholar
  88. 88.
    Warris A, Weemaes CM, Verweij PE. Multidrug resistance in Aspergillus fumigatus. N Engl J Med 2002; 347:2173–2174.PubMedCrossRefGoogle Scholar
  89. 89.
    Verweij PE, Mellado E, Melchers WJ. Multiple-triazole-resistant aspergillosis. N Engl J Med 2007; 356:1481–1483.PubMedCrossRefGoogle Scholar
  90. 90.
    van Leer-Buter C, Takes RP, Hebeda KM, Melchers WJG, Verweij PE. Aspergillosis-and a misleading sensitivity result. Lancet 2007; 370:102.PubMedCrossRefGoogle Scholar
  91. 91.
    Dannaoui E, Persat F, Monier MR, Borel E, Piens MA, Picot S. In vitro susceptibility of Aspergillus spp. Isolates to amphotericin B and itraconazole. J Antimicrob Chemother 1999; 44:553–555.PubMedCrossRefGoogle Scholar
  92. 92.
    Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002; 34:563–571.PubMedCrossRefGoogle Scholar
  93. 93.
    Denning DW, Hanson LH, Perlman AM, Stevens DA. In vitro susceptibility and synergy studies of Aspergillus species to conventional and new agents. Diagn Microbiol Infect Dis 1992; 15:21–34.PubMedCrossRefGoogle Scholar
  94. 94.
    Maesaki S, Kohno S, Kaku M, Koga H, Hara K. Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus. Antimicrob Agents Chemother 1994; 38:2843–2845.PubMedGoogle Scholar
  95. 95.
    Arikan S, Lozano-Chiu M, Paetznick V, Rex JH. In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother 2002; 46:245–247.PubMedCrossRefGoogle Scholar
  96. 96.
    Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 2002; 46:3039–3041.PubMedCrossRefGoogle Scholar
  97. 97.
    Kirkpatrick WR, Perea S, Coco BJ, Patterson TF. Efficacy of caspofungin alone and in combination with voriconazole in a Guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002; 46:2564–2568.PubMedCrossRefGoogle Scholar
  98. 98.
    Petraitis V, Petraitiene R, Sarafandi AA, Kelaher AM, Lyman CA, Casler HE, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interactions between an antifungal triazole and an echinocandin. J Infect Dis 2003; 187:1834–1843.PubMedCrossRefGoogle Scholar
  99. 99.
    Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004; 39:797–802.PubMedCrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • P. H. Chandrasekar
    • 1
  • Elias K. Manavathu
    • 1
  1. 1.Department of Internal Medicine, Wayne State University School of MedicineHarper University HospitalDetroitUSA

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