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Chapter 23 : The Impact of Antifungal Drug Resistance in the Clinic

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Abstract:

This chapter critically evaluates some common assumptions regarding antifungal resistance and highlights key clinical problems that arise when managing patients with invasive infections caused by antifungal-resistant species. Although this paper gives perhaps the first example of in vivo-acquired mutations in a fungal gene with a positive impact on in vivo fitness, all of the clinical isolates used in the study were acquired from semi-invasive infections of the oropharynx rather than the bloodstream of patients. The majority of patients with invasive mycoses probably fail therapy because of underlying host factors, rather than acquired resistance to the drug. One of the most underappreciated causes of treatment failures in species is biofilm-mediated resistance. Problems associated with timely diagnosis and early detection of antifungal resistance in species have not improved over the last two decades, as current testing approaches still rely primarily on blood cultures, which may be negative for up to 50% of patients. It is critical that the diagnostics and treatment tools to manage antifungal resistance in species be developed now, along with clinical stewardship programs to effectively integrate their use in clinic, so that we are better equipped to deal with the challenges on the horizon that will be encountered in an increasingly complex and aged population of patients in the health care system.

Citation: Lewis R, Kontoyiannis D. 2012. The Impact of Antifungal Drug Resistance in the Clinic, p 373-385. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch23

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FIGURE 1

Geographic variation in (a) species and (b) rates of fluconazole resistance reported from the ARTEMIS Global Surveillance Program, 2001 to 2007 ( ). doi:10.1128/9781555817176.ch23.f1

Citation: Lewis R, Kontoyiannis D. 2012. The Impact of Antifungal Drug Resistance in the Clinic, p 373-385. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch23
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Antifungal resistance mechanisms in species. doi:10.1128/9781555817176.ch23.f2

Citation: Lewis R, Kontoyiannis D. 2012. The Impact of Antifungal Drug Resistance in the Clinic, p 373-385. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch23
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References

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1. Abi-Said, D.,, E. Anaissie,, O. Uzun,, I. Raad,, H. Pinzcowski, and, S. Vartivarian. 1997. The epidemiology of hematogenous candidiasis caused by different Candida species. Clin. Infect. Dis. 24: 11221128.
2. Alexander, B. D.,, W. A. Schell,, J. L. Miller,, G. D. Long, and, J. R. Perfect. 2005. Candida glabrata fungemia in transplant patients receiving voriconazole after fluconazole. Transplantation 80: 868871.
3. Almirante, B.,, D. Rodriguez,, B. J. Park,, M. Cuenca-Estrella,, A. M. Planes,, M. Almela,, J. Mensa,, F. Sanchez,, J. Ayats,, M. Gimenez,, P. Saballs,, S. K. Fridkin,, J. Morgan,, J. L. Rodriguez-Tudela,, D. W. Warnock, and, A. Pahissa. 2005. Epidemiology and predictors of mortality in cases of Candida bloodstream infection: results from population-based surveillance, Barcelona, Spain, from 2002 to 2003. J. Clin. Microbiol. 43: 18291835.
4. Anderson, J. B. 2005. Evolution of antifungal-drug resistance: mechanisms and pathogen fitness. Nat. Rev. Microbiol. 3: 547556.
5. Andes, D. 2006. Pharmacokinetics and pharmacodynamics of antifungals. Infect. Dis. Clin. N. Am. 20: 679697.
6. Andes, D.,, D. J. Diekema,, M. A. Pfaller,, J. Bohrmuller,, K. Marchillo, and, A. Lepak. 2010. In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species. Antimicrob. Agents Chemother. 54: 24972506.
7. Antoniadou, A.,, H. A. Torres,, R. E. Lewis,, J. Thornby,, G. P. Bodey,, J. J. Tarrand,, X. Y. Han,, K. V. I. Rolston,, A. Safdar,, I. I. Raad, and, D. P. Kontoyiannis. 2003. Candidemia in a tertiary care cancer center. In vitro susceptibility and its association with outcome of initial antifungal therapy. Medicine 82: 309321.
8. Arendrup, M.,, T. Horn, and, N. Frimodt-Moller. 2002. In vivo pathogenicity of eight medically relevant Candida species in an animal model. Infection 30: 286291.
9. Atkinson, B. J.,, R. E. Lewis, and, D. P. Kontoyiannis. 2008. Candida lusitaniae fungemia in cancer patients: risk factors for amphotericin B failure and outcome. Med. Mycol. 46: 541546.
10. Bachmann, S. P.,, K. VandeWalle,, G. Ramage,, T. F. Patterson,, B. L. Wickes,, J. R. Graybill, and, J. L. Lopez-Ribot. 2002. In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob. Agents Chemother. 46: 35913596.
11. Baddley, J. W.,, M. Patel,, S. M. Bhavnani,, S. A. Moser, and, D. R. Andes. 2008. Association of fluconazole pharmacodynamics with mortality in patients with candidemia. Antimicrob. Agents Chemother. 52: 30223028.
12. Baran, J., Jr.,, B. Muckatira, and, R. Khatib. 2001. Candidemia before and during the fluconazole era: prevalence, type of species and approach to treatment in a tertiary care community hospital. Scand. J. Infect. Dis. 33: 137139.
13. Ben-Ami, R.,, G. Garcia-Effron,, R. E. Lewis,, K. Leventakos,, D. S. Perlin, and, D. P. Kontoyiannis. 2009. Mutations in Candida albicans FKS1 conferring echinocandin resistance are associated with attenuated virulence. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
14. Berenguer, J.,, M. Buck,, F. Witebsky,, F. Stock,, P. A. Pizzo, and, T. J. Walsh. 1993. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn. Microbiol. Infect. Dis. 17: 103109.
15. Blot, S. I., and, K. H. Vandewoude. 2003. Estimating attributable mortality of candidemia: clinical judgement vs. matched cohort studies. Eur. J. Clin. Microbiol. Infect. D 22: 132133.
16. Blot, S. I.,, K. H. Vandewoude,, E. A. Hoste, and, F. A. Colardyn. 2002. Effects of nosocomial candidemia on outcomes of critically ill patients. Am. J. Med. 113: 480485.
17. Bodey, G. P.,, M. Mardani,, H. A. Hanna,, M. Boktour,, J. Abbas,, E. Girgawy,, R. Y. Hachem,, D. P. Kontoyiannis, and, I. I. Raad. 2002. The epidemiology of Candida glabrata and Candida albicans fungemia in immunocompromised patients with cancer. Am. J. Med. 112: 380385.
18. Bustamante, C. I. 2005. Treatment of Candida infection: a view from the trenches! Curr. Opin. Infect. Dis. 18: 490495.
19. Cano, M. V.,, J. F. Perz,, A. S. Craig,, M. Liu,, G. M. Lyon,, M. E. Brandt,, T. J. Lott,, B. A. Lasker,, F. F. Barrett,, M. M. McNeil,, W. Schaffner, and, R. A. Hajjeh. 2005. Candidemia in pediatric outpatients receiving home total parenteral nutrition. Med. Mycol. 43: 219225.
20. Casadevall, A., and, L. A. Pirofski. 1999. Host-pathogen interactions: redefining the basic concepts of virulence and pathogenicity. Infect. Immun. 67: 37033713.
21. Castanheira, M.,, L. N. Woosley,, D. J. Diekema,, S. A. Messer,, R. N. Jones, and, M. A. Pfaller. 2010. Low prevalence of fks1 hot spot 1 mutations in a worldwide collection of Candida strains. Antimicrob. Agents Chemother. 54: 26552659.
22. Chamilos, G.,, M. Luna,, R. E. Lewis,, G. P. Bodey,, R. Chemaly,, J. J. Tarrand,, A. Safdar,, I. I. Raad, and, D. P. Kontoyiannis. 2006. 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 91: 986989.
23. Chapeland-Leclerc, F.,, C. Hennequin,, N. Papon,, T. Noel,, A. Girard,, G. Socie,, P. Ribaud, and, C. Lacroix. 2010. Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient. Antimicrob. Agents Chemother. 54: 13601362.
24. Chen, S. C., and, D. P. Kontoyiannis. 2010. New molecular and surrogate biomarker-based tests in the diagnosis of bacterial and fungal infection in febrile neutropenic patients. Curr. Opin. Infect. Dis. 23: 567577.
25. Clinical and Laboratory Standards Institute. 2008. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard—Third Edition. Clinical and Laboratory Standards Institute, Wayne, PA.
26. Cowen, L. E.,, L. M. Kohn, and, J. B. Anderson. 2001. Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans. J. Bacteriol. 183: 29712978.
27. Diekema, D. J.,, S. A. Messer,, L. B. Boyken,, R. J. Hollis,, J. Kroeger,, S. Tendolkar, and, M. A. Pfaller. 2009. In vitro activity of seven systemically active antifungal agents against a large global collection of rare Candida species as determined by CLSI broth microdilution methods. J. Clin. Microbiol. 47: 31703177.
28. Diekema, D. J.,, S. A. Messer,, R. J. Hollis,, R. P. Wenzel, and, M. A. Pfaller. 1997. An outbreak of Candida parapsilosis prosthetic valve endocarditis. Diagn. Microbiol. Infect. Dis. 29: 147153.
29. Dodgson, A. R.,, C. Pujol,, D. W. Denning,, D. R. Soll, and, A. J. Fox. 2003. Multilocus sequence typing of Candida glabrata reveals geographically enriched clades. J. Clin. Microbiol. 41: 57095717.
30. Donlan, R. M., and, J. W. Costerton. 2002. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 15: 167193.
31. Dube, M. P.,, P. N. R. Heseltine,, M. G. Rinaldi,, S. Evans, and, B. Zawacki. 1994. Fungemia and colonization with nystatin-resistant Candida rugosa in a burn unit. Clin. Infect. Dis. 18: 7782.
32. Espinel-Ingroff, A.,, F. Barchiesi,, M. Cuenca-Estrella,, M. A. Pfaller,, M. Rinaldi,, J. L. Rodriguez-Tudela, and, P. E. Verweij. 2005. International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole. J. Clin. Microbiol. 43: 38843889.
33. Falagas, M. E.,, K. E. Apostolou, and, V. D. Pappas. 2006. Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies. Eur. J. Clin. Microbiol. Infect. Dis. 25: 419425.
34. Fernandez, J.,, B. L. Erstad,, W. Petty, and, D. E. Nix. 2009. Time to positive culture and identification for Candida blood stream infections. Diagn. Microbiol. Infect. Dis. 64: 402407.
35. Ferrari, S.,, F. Ischer,, D. Calabrese,, B. Posteraro,, M. Sanguinetti,, G. Fadda,, B. Rohde,, C. Bauser,, O. Bader, and, D. Sanglard. 2009. Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence. PLoS Pathog. 5: e1000268.
36. Fidel, P. L., Jr.,, J. A. Vazquez, and, J. D. Sobel. 1999. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin. Microbiol. Rev. 12: 80–96, CP2.
37. Forrest, G. N.,, E. Weekes, and, J. K. Johnson. 2008. Increasing incidence of Candida parapsilosis candidemia with caspofungin usage. J. Infect. 56: 126129.
38. Garcia-Effron, G.,, S. K. Katiyar,, S. Park,, T. D. Edlind, and, D. S. Perlin. 2008. 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. 52: 23052312.
39. Garcia-Effron, G.,, D. P. Kontoyiannis,, R. E. Lewis, and, D. S. Perlin. 2008. Caspofungin-resistant Candida tropicalis strains causing breakthrough fungemia in patients at high risk for hematologic malignancies. Antimicrob. Agents Chemother. 52: 41814183.
40. Garey, K. W.,, M. Rege,, M. P. Pai,, D. E. Mingo,, K. J. Suda,, R. S. Turpin, and, D. T. Bearden. 2006. Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin. Infect. Dis. 43: 2531.
41. Ghannoum, M. A.,, R. J. Jurevic,, P. K. Mukherjee,, F. Cui,, M. Sikaroodi,, A. Naqvi, and, P. M. Gillevet. 2010. Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog. 6: e1000713.
42. Graybill, J. R.,, E. Montalbo,, W. R. Kirkpatrick,, M. F. Luther,, S. G. Revankar, and, T. F. Patterson. 1998. Fluconazole versus Candida albicans: a complex relationship. Antimicrob. Agents Chemother. 42: 29382942.
43. Gudlaugsson, O.,, S. Gillespie,, K. Lee,, J. V. Berg,, J. F. Hu,, S. Messer,, L. Herwaldt,, M. Pfaller, and, D. Diekema. 2003. Attributable mortality of nosocomial candidemia, revisited. Clin. Infect. Dis. 37: 11721177.
44. Gulia, J.,, S. Aryal,, H. Saadlla, and, A. F. Shorr. 2010. Healthcare-associated candidemia—a distinct entity? J. Hosp. Med. 5: 298301.
45. Hachem, R.,, H. Hanna,, D. Kontoyiannis,, Y. Jiang, and, I. Raad. 2008. The changing epidemiology of invasive candidiasis: Candida glabrata and Candida krusei as the leading causes of candidemia in hematologic malignancy. Cancer 112: 24932499.
46. Hajjeh, R. A.,, A. N. Sofair,, L. H. Harrison,, G. M. Lyon,, B. A. Arthington-Skaggs,, S. A. Mirza,, M. Phelan,, J. Morgan,, W. Lee-Yang,, M. A. Ciblak,, L. E. Benjamin,, L. T. Sanza,, S. Huie,, S. F. Yeo,, M. E. Brandt, and, D. W. Warnock. 2004. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J. Clin. Microbiol. 42: 15191527.
47. Hawkins, J. L., and, L. M. Baddour. 2003. Candida lusitaniae infections in the era of fluconazole availability. Clin. Infect. Dis. 36: E14–E18.
48. Horn, D. L.,, D. Neofytos,, E. J. Anaissie,, J. A. Fishman,, W. J. Steinbach,, A. J. Olyaei,, K. A. Marr,, M. A. Pfaller,, C. H. Chang, and, K. M. Webster. 2009. Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry. Clin. Infect. Dis. 48: 16951703.
49. Ibrahim, E. H.,, G. Sherman,, S. Ward,, V. J. Fraser, and, M. H. Kollef. 2000. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 118: 146155.
50. Jensen, J.,, P. Munoz,, J. Guinea,, M. Rodriguez-Creixems,, T. Pelaez, and, E. Bouza. 2007. Mixed fungemia: incidence, risk factors, and mortality in a general hospital. Clin. Infect. Dis. 44: e109–e114.
51. Kanafani, Z. A., and, J. R. Perfect. 2008. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin. Infect. Dis. 46: 120128.
52. Kartsonis, N.,, J. Killar,, L. Mixson,, C. M. Hoe,, C. Sable,, K. Bartizal, and, M. Motyl. 2005. Caspofungin susceptibility testing of isolates from patients with esophageal candidiasis or invasive candidiasis: relationship of MIC to treatment outcome. Antimicrob. Agents Chemother. 49: 36163623.
53. Klevay, M. J.,, E. J. Ernst,, J. L. Hollanbaugh,, J. G. Miller,, M. A. Pfaller, and, D. J. Diekema. 2008. Therapy and outcome of Candida glabrata versus Candida albicans bloodstream infection. Diagn. Microbiol. Infect. Dis. 60: 273277.
54. Klevay, M. J.,, D. L. Horn,, D. Neofytos,, M. A. Pfaller, and, D. J. Diekema. 2009. Initial treatment and outcome of Candida glabrata versus Candida albicans bloodstream infection. Diagn. Microbiol. Infect. Dis. 64: 152157.
55. Kontoyiannis, D. P. 2009. Echinocandin-based initial therapy in fungemic patients with cancer: a focus on recent guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 49: 638639. (Author’s reply, 49: 639–640.)
56. Kontoyiannis, D. P.,, G. P. Bodey, and, C. S. Mantzoros. 2001. Fluconazole vs. amphotericin B for the management of candidaemia in adults: a meta-analysis. Mycoses 44: 125135.
57. Kontoyiannis, D. P., and, R. E. Lewis. 2002. Antifungal drug resistance of pathogenic fungi. Lancet 359: 11351144.
58. Kovacicova, G.,, M. Lovaszova,, J. Hanzen,, A. Roidova,, F. Mateicka,, M. Lesay, and, V. Krcmery. 2001. Persistent fungemia—risk factors and outcome in 40 episodes. J. Chemother. 13: 429433.
59. Kuhn, D. M.,, T. George,, J. Chandra,, P. K. Mukherjee, and, M. A. Ghannoum. 2002. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob. Agents Chemother. 46: 17731780.
60. Kurtz, M. B.,, G. Abruzzo,, A. Flattery,, K. Bartizal,, J. A. Marrinan,, W. Li,, J. Milligan,, K. Nollstadt, and, C. M. Douglas. 1996. Characterization of echinocandin-resistant mutants of Candida albicans: genetic, biochemical, and virulence studies. Infect. Immun. 64: 32443251.
61. Lattif, A. A.,, P. K. Mukherjee,, J. Chandra,, K. Swindell,, S. R. Lockhart,, D. J. Diekema,, M. A. Pfaller, and, M. A. Ghannoum. 2010. Characterization of biofilms formed by Candida parapsilosis, C. metapsilosis, and C. orthopsilosis. Int. J. Med. Microbiol. 300: 265270.
62. Leroy, O.,, J. P. Gangneux,, P. Montravers,, J. P. Mira,, F. Gouin,, J. P. Sollet,, J. Carlet,, J. Reynes,, M. Rosenheim,, B. Regnier, and, O. Lortholary. 2009. Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit. Care Med. 37: 16121618.
63. Lin, M. Y.,, Y. Carmeli,, J. Zumsteg,, E. L. Flores,, J. Tolentino,, P. Sreeramoju, and, S. G. Weber. 2005. Prior antimicrobial therapy and risk for hospital-acquired Candida glabrata and Candida krusei fungemia: a case-case-control study. Antimicrob. Agents Chemother. 49: 45554560.
64. MacArthur, R. D.,, M. Miller,, T. Albertson,, E. Panacek,, D. Johnson,, L. Teoh, and, W. Barchuk. 2004. Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial. Clin. Infect. Dis. 38: 284288.
65. Marr, K. A. 2000. The changing spectrum of candidemia in oncology patients: therapeutic implications. Curr. Opin. Infect. Dis. 13: 615620.
66. Martins, M. D.,, M. Lozano-Chiu, and, J. H. Rex. 1998. Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 27: 12911294.
67. McClenny, N. B.,, H. H. Fei,, E. J. Baron,, A. C. Gales,, A. Houston,, R. J. Hollis, and, M. A. Pfaller. 2002. Change in colony morphology of Candida lusitaniae in association with development of amphotericin B resistance. Antimicrob. Agents Chemother. 46: 13251328.
68. Morrell, M.,, V. J. Fraser, and, M. H. Kollef. 2005. Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob. Agents Chemother. 49: 36403645.
69. National Committee for Clinical Laboratory Standards. 2004. Methods for Antifungal Disk Diffusion Susceptibility Testing of Yeasts; Approved Guideline M44-A. National Committee for Clinical Laboratory Standards, Wayne, PA.
70. Neofytos, D.,, J. A. Fishman,, D. Horn,, E. Anaissie,, C. H. Chang,, A. Olyaei,, M. Pfaller,, W. J. Steinbach,, K. M. Webster, and, K. A. Marr. 2010. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients. Transpl. Infect. Dis. 12: 220229.
71. Neofytos, D.,, D. Horn,, E. Anaissie,, W. Steinbach,, A. Olyaei,, J. Fishman,, M. Pfaller,, C. Chang,, K. Webster, and, K. Marr. 2009. 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. 48: 265273.
72. Nett, J., and, D. Andes. 2006. Candida albicans biofilm development, modeling a host-pathogen interaction. Curr. Opin. Microbiol. 9: 340345.
73. Nett, J.,, L. Lincoln,, K. Marchillo, and, D. Andes. 2007. Beta-1,3 glucan as a test for central venous catheter biofilm infection. J. Infect. Dis. 195: 17051712.
74. Nett, J.,, L. Lincoln,, K. Marchillo,, R. Massey,, K. Holoyda,, B. Hoff,, M. VanHandel, and, D. Andes. 2007. Putative role of beta-1,3 glucans in Candida albicans biofilm resistance. Antimicrob. Agents Chemother. 51: 510520.
75. Nett, J. E.,, K. M. Guite,, A. Ringeisen,, K. A. Holoyda, and, D. R. Andes. 2008. Reduced biocide susceptibility in Candida albicans biofilms. Antimicrob. Agents Chemother. 52: 34113413.
76. Ostrosky-Zeichner, L.,, D. Kontoyiannis,, J. Raffalli,, K. M. Mullane,, J. Vazquez,, E. J. Anaissie,, J. Lipton,, P. Jacobs,, J. H. van Rensburg,, J. H. Rex,, W. Lau,, D. Facklam, and, D. N. Buell. 2005. 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. 24: 654661.
77. Ostrosky-Zeichner, L., and, P. G. Pappas. 2006. Invasive candidiasis in the intensive care unit. Crit. Care Med. 34: 857863.
78. Oxman, D. A.,, J. K. Chow,, G. Frendl,, S. Hadley,, S. Hershkovitz,, P. Ireland,, L. A. McDermott,, K. Tsai,, F. M. Marty,, D. P. Kontoyiannis, and, Y. Golan. 2010. Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern? J. Antimicrob. Chemother. 65: 14501465.
79. Pai, M. P., and, S. L. Pendland. 2003. Antifungal susceptibility testing in teaching hospitals. Ann. Pharmacother. 37: 192196.
80. Pai, M. P.,, R. S. Turpin, and, K. W. Garey. 2007. Association of fluconazole area under the concentration-time curve/MIC and dose/MIC ratios with mortality in nonneutropenic patients with candidemia. Antimicrob. Agents Chemother. 51: 3539.
81. Pappas, P. G. 2006. Invasive candidiasis. Infect. Dis. Clin. N. Am. 20: 485506.
82. Pappas, P. G.,, C. A. Kauffman,, D. Andes,, D. K. Benjamin, Jr.,, T. F. Calandra,, J. E. Edwards, Jr.,, S. G. Filler,, J. F. Fisher,, B. J. Kullberg,, L. Ostrosky-Zeichner,, A. C. Reboli,, J. H. Rex,, T. J. Walsh, and, J. D. Sobel. 2009. Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 48: 503535.
83. Pappas, P. G.,, J. H. Rex,, J. Lee,, R. J. Hamill,, R. A. Larsen,, W. Powderly,, C. A. Kauffman,, N. Hyslop,, J. E. Mangino,, S. Chapman,, H. W. Horowitz,, J. E. Edwards, and, W. E. Dismukes. 2003. A prospective observational study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin. Infect. Dis. 37: 634643.
84. Pasqualotto, A. C.,, W. L. Nedel,, T. S. Machado, and, L. C. Severo. 2006. Risk factors and outcome for nosocomial breakthrough candidaemia. J. Infect. 52: 216222.
85. Pasqualotto, A. C.,, R. A. Zimerman,, S. H. Alves,, V. R. Aquino,, D. Branco,, D. Wiltgen,, A. do Amaral,, R. Cechinel,, S. M. Colares,, I. G. da Rocha,, L. C. Severo, and, T. C. Sukiennik. 2008. Take control over your fluconazole prescriptions: the growing importance of Candida glabrata as an agent of candidemia in Brazil. Infect. Control Hosp. Epidemiol. 29: 898899.
86. Perlin, D. S. 2009. Antifungal drug resistance: do molecular methods provide a way forward? Curr. Opin. Infect. Dis. 22: 568573.
87. Pfaller, M. A.,, L. Boyken,, R. J. Hollis,, J. Kroeger,, S. A. Messer,, S. Tendolkar, and, D. J. Diekema. 2008. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J. Clin. Microbiol. 46: 150156.
88. Pfaller, M. A.,, L. Boyken,, R. J. Hollis,, J. Kroeger,, S. A. Messer,, S. Tendolkar,, R. N. Jones,, J. Turnidge, and, D. J. Diekema. 2010. Wild-type MIC distributions and epidemiological cutoff values for the echinocandins and Candida spp. J. Clin. Microbiol. 48: 5256.
89. Pfaller, M. A.,, L. Boyken,, R. J. Hollis,, S. A. Messer,, S. Tendolkar, and, D. J. Diekema. 2006. In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance. J. Clin. Microbiol. 44: 760763.
90. Pfaller, M. A.,, M. Castanheira,, D. J. Diekema,, S. A. Messer,, G. J. Moet, and, R. N. Jones. 2010. Comparison of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Etest methods with the CLSI broth microdilution method for echinocandin susceptibility testing of Candida species. J. Clin. Microbiol. 48: 15921599.
91. Pfaller, M. A.,, M. Castanheira,, S. A. Messer,, G. J. Moet, and, R. N. Jones. 2010. Variation in Candida spp. distribution and antifungal resistance rates among bloodstream infection isolates by patient age: report from the SENTRY Antimicrobial Surveillance Program (2008–2009). Diagn. Microbiol. Infect. Dis. 68: 278283.
92. Pfaller, M. A., and, D. J. Diekema. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20: 133163.
93. Pfaller, M. A., and, D. J. Diekema. 2010. Epidemiology of invasive mycoses in North America. Crit. Rev. Microbiol. 36: 153.
94. Pfaller, M. A.,, D. J. Diekema,, A. L. Colombo,, C. Kibbler,, K. P. Ng,, D. L. Gibbs, and, V. A. Newell. 2006. Candida rugosa, an emerging fungal pathogen with resistance to azoles: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program. J. Clin. Microbiol. 44: 35783582.
95. Pfaller, M. A.,, D. J. Diekema,, D. L. Gibbs,, V. A. Newell,, R. Barton,, H. Bijie,, J. Bille,, S. C. Chang,, M. da Luz Martins,, A. Duse,, D. Dzierzanowska,, D. Ellis,, J. Finquelievich,, I. Gould,, D. Gur,, A. Hoosen,, K. Lee,, N. Mallatova,, M. Mallie,, N. G. Peng,, G. Petrikos,, A. Santiago,, J. Trupl,, A. M. VanDen Abeele,, J. Wadula, and, M. Zaidi. 2010. Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global Antifungal Surveillance Program. Diagn. Microbiol. Infect. Dis. 67: 162171.
96. Pfaller, M. A.,, D. J. Diekema,, D. L. Gibbs,, V. A. Newell,, H. Bijie,, D. Dzierzanowska,, N. N. Klimko,, V. Letscher-Bru,, M. Lisalova,, K. Muehlethaler,, C. Rennison, and, M. Zaidi. 2009. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: 10.5-year analysis of susceptibilities of noncandidal yeast species to fluconazole and voriconazole determined by CLSI standardized disk diffusion testing. J. Clin. Microbiol. 47: 117123.
97. Pfaller, M. A.,, D. J. Diekema,, D. L. Gibbs,, V. A. Newell,, D. Ellis,, V. Tullio,, A. Rodloff,, W. Fu, and, T. A. Ling. 2010. Results from the ARTEMIS DISK Global Antifungal Surveillance Study, 1997 to 2007: a 10.5-year analysis of susceptibilities of Candida species to fluconazole and voriconazole as determined by CLSI standardized disk diffusion. J. Clin. Microbiol. 48: 13661377.
98. Pfaller, M. A.,, D. J. Diekema,, D. L. Gibbs,, V. A. Newell,, E. Nagy,, S. Dobiasova,, M. Rinaldi,, R. Barton, and, A. Veselov. 2008. Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J. Clin. Microbiol. 46: 515521.
99. Pfaller, M. A.,, D. J. Diekema,, D. L. Gibbs,, V. A. Newell,, K. P. Ng,, A. Colombo,, J. Finquelievich,, R. Barnes, and, J. Wadula. 2008. 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. 46: 842849.
100. Pfaller, M. A.,, D. J. Diekema,, L. Ostrosky-Zeichner,, J. H. Rex,, B. D. Alexander,, D. Andes,, S. D. Brown,, V. Chaturvedi,, M. A. Ghannoum,, C. C. Knapp,, D. J. Sheehan, and, T. J. Walsh. 2008. Correlation of MIC with outcome for Candida species tested against caspofungin, anidulafungin, and micafungin: analysis and proposal for interpretive MIC breakpoints. J. Clin. Microbiol. 46: 26202629.
101. Pfaller, M. A.,, S. A. Messer,, R. J. Hollis,, L. Boyken,, S. Tendolkar,, J. Kroeger, and, D. J. Diekema. 2009. Variation in susceptibility of bloodstream isolates of Candida glabrata to fluconazole according to patient age and geographic location in the United States in 2001 to 2007. J. Clin. Microbiol. 47: 31853190.
102. Pfaller, M. A.,, J. H. Rex, and, M. G. Rinaldi. 1996. Antifungal susceptibility testing: technical advances and potential clinical applications. Clin. Infect. Dis. 24: 776784.
103. Pfaller, M. A.,, S. Wey,, T. Gerarden,, A. Houston, and, R. P. Wenzel. 1989. Susceptibility of nosocomial isolates of Candida species to LY121019 and other antifungal agents. Diagn. Microbiol. Infect. Dis. 12: 14.
104. Playford, E. G.,, D. Marriott,, Q. Nguyen,, S. Chen,, D. Ellis,, M. Slavin, and, T. C. Sorrell. 2008. Candidemia in nonneutropenic critically ill patients: risk factors for non-albicans Candida spp. Crit. Care Med. 36: 20342039.
105. Rex, J. H.,, M. A. Pfaller,, J. N. Galgiani,, M. S. Bartlett,, A. Espinel-Ingroff,, M. A. Ghannoum,, M. Lancaster,, F. C. Odds,, M. G. Rinaldi,, T. J. Walsh, and, A. L. Barry. 1997. Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards. Clin. Infect. Dis. 24: 235247.
106. Rex, J. H.,, M. A. Pfaller,, T. J. Walsh,, V. Chaturvedi,, A. Espinel-Ingroff,, M. A. Ghannoum,, L. L. Gosey,, F. C. Odds,, M. G. Rinaldi,, D. J. Sheehan, and, D. W. Warnock. 2001. Antifungal susceptibility testing: practical aspects and current challenges. Clin. Microbiol. Rev. 14: 643658.
107. Richet, H.,, P. Roux,, C. Des Champs,, Y. Esnault, and, A. Andremont. 2002. Candidemia in French hospitals: incidence rates and characteristics. Clin. Microbiol. Infect. 8: 405412.
108. Sanglard, D., and, F. C. Odds. 2002. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect. Dis. 2: 7385.
109. Shepard, J. R.,, R. M. Addison,, B. D. Alexander,, P. Della-Latta,, M. Gherna,, G. Haase,, G. Hall,, J. K. Johnson,, W. G. Merz,, H. Peltroche-Llacsahuanga,, H. Stender,, R. A. Venezia,, D. Wilson,, G. W. Procop,, F. Wu, and, M. J. Fiandaca. 2008. Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles. J. Clin. Microbiol. 46: 5055.
110. Shorr, A. F.,, V. Gupta,, X. Sun,, R. S. Johannes,, J. Spalding, and, Y. P. Tabak. 2009. Burden of early-onset candidemia: analysis of culture-positive bloodstream infections from a large U.S. database. Crit. Care Med. 37: 2519–2526; quiz, 2535.
111. Shorr, A. F.,, D. R. Lazarus,, J. H. Sherner,, W. L. Jackson,, M. Morrel,, V. J. Fraser, and, M. H. Kollef. 2007. Do clinical features allow for accurate prediction of fungal pathogenesis in bloodstream infections? Potential implications of the increasing prevalence of non-albicans candidemia. Crit. Care Med. 35: 10771083.
112. Sipsas, N. V.,, R. E. Lewis,, J. Tarrand,, R. Hachem,, K. V. Rolston,, I. I. Raad, and, D. P. Kontoyiannis. 2009. Candidemia in patients with hematologic malignancies in the era of new antifungal agents (2001–2007): stable incidence but changing epidemiology of a still frequently lethal infection. Cancer 115: 47454752.
113. Slavin, M. A.,, T. C. Sorrell,, D. Marriott,, K. A. Thursky,, Q. Nguyen,, D. H. Ellis,, C. O. Morrissey, and, S. C. Chen. 2010. Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death. J. Antimicrob. Chemother. 65: 10421051.
114. Trick, W. E.,, S. K. Fridkin,, J. R. Edwards,, R. A. Hajjeh, and, R. P. Gaynes. 2002. Secular trend of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin. Infect. Dis. 35: 627630.
115. Trofa, D.,, A. Gacser, and, J. D. Nosanchuk. 2008. Candida parapsilosis, an emerging fungal pathogen. Clin. Microbiol. Rev. 21: 606625.
116. Viscoli, C.,, C. Girmenia,, A. Marinus,, L. Collette,, P. Martino,, B. Vandercam,, C. Doyen,, B. Lebeau,, D. Spence,, V. Krcmery,, B. De Pauw, and, F. Meunier. 1999. Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin. Infect. Dis. 28: 10711079.
117. Walsh, T. J.,, H. Teppler,, G. R. Donowitz,, J. A. Maertens,, L. R. Baden,, A. Dmoszynska,, O. A. Cornely,, M. R. Bourque,, R. J. Lupinacci,, C. A. Sable, and, B. E. dePauw. 2004. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N. Engl. J. Med. 351: 13911402.
118. Wenzel, R. P. 1995. Nosocomial candidemia: risk factors and attributable mortality. Clin. Infect. Dis. 20: 15311534.
119. Wey, S. B.,, M. Mori,, M. A. Pfaller,, R. F. Woolson, and, R. P. Wenzel. 1988. Hospital acquired candidemia: the attributable mortality and excess length of stay. Arch. Intern. Med. 148: 26422645.
120. Wilson, D. A.,, M. J. Joyce,, L. S. Hall,, L. B. Reller,, G. D. Roberts,, G. S. Hall,, B. D. Alexander, and, G. W. Procop. 2005. Multicenter evaluation of a Candida albicans peptide nucleic acid fluorescent in situ hybridization probe for characterization of yeast isolates from blood cultures. J. Clin. Microbiol. 43: 29092912.
121. Wisplinghoff, H.,, T. Bischoff,, S. M. Tallent,, H. Seifert,, R. P. Wenzel, and, M. B. Edmond. 2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39: 309317.
122. Zaoutis, T. E.,, J. Argon,, J. Chu,, J. A. Berlin,, T. J. Walsh, and, C. Feudtner. 2005. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin. Infect. Dis. 41: 12321239.
123. Zaoutis, T. E.,, H. M. Greves,, E. Lautenbach,, W. B. Bilker, and, S. E. Coffin. 2004. Risk factors for disseminated candidiasis in children with candidemia. Pediatr. Infect. Dis. J. 23: 635641.

Tables

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TABLE 1

Predictors of poor outcome in recent prospective multicenter observational cohort studies of invasive candidiasis

Citation: Lewis R, Kontoyiannis D. 2012. The Impact of Antifungal Drug Resistance in the Clinic, p 373-385. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch23
Generic image for table
TABLE 2

Circumstances contributing to clinical resistance in patients with invasive candidiasis

Citation: Lewis R, Kontoyiannis D. 2012. The Impact of Antifungal Drug Resistance in the Clinic, p 373-385. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch23

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