No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Filamentous Fungi

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • PDF
    474.28 Kb
  • XML
    291.06 Kb
  • HTML
    294.56 Kb
  • Authors: Margaret V. Powers-Fletcher1, Brian A. Kendall2,3, Allen T. Griffin4, Kimberly E. Hanson5,6
  • Editors: Randall T. Hayden7, Donna M. Wolk8, Karen C. Carroll9, Yi-Wei Tang10
    Affiliations: 1: Department of Pathology; 2: Department of Pathology; 3: Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132; 4: Owensboro Health, Owensboro, KY 42303; 5: Department of Pathology; 6: Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT 84132; 7: Clinical and Molecular Microbiology, Department of Pathology, St. Jude’s Children’s Research Hospital, Memphis, TN; 8: Geisinger Clinic, Department of Laboratory Medicine, Danville, PA; 9: Johns Hopkins University Hospital, Baltimore, MD; 10: Clinical Microbiology Service, Memorial Sloane-Kettering Institute, New York, NY
  • Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0002-2015
  • Received 02 March 2015 Accepted 08 June 2015 Published 03 June 2016
  • Kimberly E. Hanson, [email protected]
image of Filamentous Fungi
    Preview this microbiology spectrum article:
    Zoom in

    Filamentous Fungi, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/4/3/DMIH2-0002-2015-1.gif /docserver/preview/fulltext/microbiolspec/4/3/DMIH2-0002-2015-2.gif
  • Abstract:

    Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in immunocompromised patients. The host immune response plays an essential role in determining the course of exposure to potential fungal pathogens. Depending on the effectiveness of immune response and the burden of organism exposure, fungi can either be cleared or infection can occur and progress to a potentially fatal invasive disease. Nonspecific cellular immunity (i.e., neutrophils, natural killer [NK] cells, and macrophages) combined with T-cell responses are the main immunologic mechanisms of protection. The most common potential mold pathogens include certain hyaline hyphomycetes, endemic fungi, the , and some dematiaceous fungi. Laboratory diagnostics aimed at detecting and differentiating these organisms are crucial to helping clinicians make informed decisions about treatment. The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.

  • Citation: Powers-Fletcher M, Kendall B, Griffin A, Hanson K. 2016. Filamentous Fungi. Microbiol Spectrum 4(3):DMIH2-0002-2015. doi:10.1128/microbiolspec.DMIH2-0002-2015.


1. Douglas LJ. 2003. Candida biofilms and their role in infection. Trends Microbiol 11:30–36. [PubMed][CrossRef]
2. Warenda AJ, Kauffman S, Sherrill TP, Becker JM, Konopka JB. 2003. Candida albicans septin mutants are defective for invasive growth and virulence. Infect Immun 71:4045–4051. [PubMed][CrossRef]
3. Cole GT. 1996. Basic Biology of Fungi. In Baron S (ed), Medical Microbiology, 4th ed. University of Texas Medical Branch at Galveston, Galveston, TX.
4. Hawksworth DL. 2011. A new dawn for the naming of fungi: impacts of decisions made in Melbourne in July 2011 on the future publication and regulation of fungal names. IMA Fungus 2:155–162. [PubMed][CrossRef]
5. O’Brien HE, Parrent JL, Jackson JA, Moncalvo JM, Vilgalys R. 2005. Fungal community analysis by large-scale sequencing of environmental samples. Appl Environ Microbiol 71:5544–5550. [PubMed][CrossRef]
6. Köhler JR, Casadevall A, Perfect J. 2014. The spectrum of fungi that infects humans. Cold Spring Harb Perspect Med 5:a019273. [PubMed][CrossRef]
7. Sutton DA, Fothergill AW, Rinaldi MG. 1998. Guide to Clinically Significant Fungi. Williams and Wilkins, MD.
8. Larone DH. 2011. Medically Important Fungi: A Guide to Identification, 5th ed. ASM Press, Washington, DC.
9. Brandt ME, Gomez BL, Warnock DW. 2011. Histoplasma, Blastomyces, Coccidioides, and Other Dimorphic Fungi Causing Systemic Mycoses. In Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW (ed), Manual of Clinical Microbiology, 10th ed, vol 2. ASM Press, Washington, DC. [CrossRef]
10. LaRocco M. 2007. Mycology and Antifungal Susceptibility Testing. In Garcia LS (ed), Clinical Microbiology Procedures Handbook, 3rd ed, vol 2. ASM Press, Washington, DC.
11. U.S. Department of Health and Human Services. 2009. Biosafety in Microbiological and Biomedical Laboratories, 5th ed. Centers for Disease Control and Prevention/National Institutes of Health, Washington, DC.
12. Emmons CW. 1949. Isolation of Histoplasma capsulatum from soil. Public Health Rep 64:892–896. [PubMed][CrossRef]
13. Garcia-Guiñon A, Torres-Rodríguez JM, Ndidongarte DT, Cortadellas F, Labrín L. 2009. Disseminated histoplasmosis by Histoplasma capsulatum var. duboisii in a paediatric patient from the Chad Republic, Africa. Eur J Clin Microbiol Infect Dis 28:697–699. [PubMed][CrossRef]
14. Baddley JW, Winthrop KL, Patkar NM, Delzell E, Beukelman T, Xie F, Chen L, Curtis JR. 2011. Geographic distribution of endemic fungal infections among older persons, United States. Emerg Infect Dis 17:1664–1669. [PubMed][CrossRef]
15. Guarner J, Brandt ME. 2011. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 24:247–280. [PubMed][CrossRef]
16. Newman SL, Smulian AG. 2013. Iron uptake and virulence in Histoplasma capsulatum. Curr Opin Microbiol 16:700–707. [PubMed][CrossRef]
17. Moore M. 1955. Morphologic variation in tissue of the organisms of the blastomycoses and of histoplasmosis. Am J Pathol 31:1049–1063. [PubMed]
18. Saccente M, Woods GL. 2010. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev 23:367–381. [PubMed][CrossRef]
19. Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, Kauffman CA. 2008. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis 46:1801–1812. [PubMed][CrossRef]
20. Taxy JB. 2007. Blastomycosis: contributions of morphology to diagnosis: a surgical pathology, cytopathology, and autopsy pathology study. Am J Surg Pathol 31:615–623. [PubMed][CrossRef]
21. Pfaller MA, Diekema DJ. 2010. Epidemiology of invasive mycoses in North America. Crit Rev Microbiol 36:1–53. [PubMed][CrossRef]
22. Fisher FS, Bultman MW, Johnson SM, Pappagianis D, Zaborsky E. 2007. Coccidioides niches and habitat parameters in the southwestern United States: A matter of scale. Ann N Y Acad Sci 1111:47–72. [PubMed][CrossRef]
23. Adam RD, Elliott SP, Taljanovic MS. 2009. The spectrum and presentation of disseminated coccidioidomycosis. Am J Med 122:770–777. [PubMed][CrossRef]
24. Huppert M, Sun SH, Harrison JL. 1982. Morphogenesis throughout saprobic and parasitic cycles of Coccidioides immitis. Mycopathologia 78:107–122. [PubMed][CrossRef]
25. Converse JL. 1955. Growth of spherules of Coccidioides immitis in a chemically defined liquid medium. Proc Soc Exp Biol Med 90:709–711. [PubMed][CrossRef]
26. Nicas M, Hubbard A. 2002. A risk analysis for airborne pathogens with low infectious doses: application to respirator selection against Coccidioides immitis spores. Risk Anal 22:1153–1163. [PubMed][CrossRef]
27. Yilmaz N, Visagie CM, Houbraken J, Frisvad JC, Samson RA. 2014. Polyphasic taxonomy of the genus Talaromyces. Stud Mycol 78:175–341. [PubMed][CrossRef]
28. Barros MB, de Almeida Paes R, Schubach AO. 2011. Sporothrix schenckii and sporotrichosis. Clin Microbiol Rev 24:633–654. [PubMed][CrossRef]
29. Aung AK, Teh BM, McGrath C, Thompson PJ. 2013. Pulmonary sporotrichosis: case series and systematic analysis of literature on clinico-radiological patterns and management outcomes. Med Mycol 51:534–544. [PubMed][CrossRef]
30. Satterwhite TK, Kageler WV, Conklin RH, Portnoy BL, DuPont HL. 1978. Disseminated sporotrichosis. JAMA 240:771–772. [PubMed][CrossRef]
31. Cooper CR Jr, Haycocks NG. 2000. Penicillium marneffei: An insurgent species among the penicillia. J Eukaryot Microbiol 47:24–28. [PubMed][CrossRef]
32. Duong TA. 1996. Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clin Infect Dis 23:125–130. [PubMed][CrossRef]
33. Lyratzopoulos G, Ellis M, Nerringer R, Denning DW. 2002. Invasive infection due to Penicillium species other than P. marneffei. J Infect 45:184–195. [PubMed][CrossRef]
34. Cao C, Liang L, Wang W, Luo H, Huang S, Liu D, Xu J, Henk DA, Fisher MC. 2011. Common reservoirs for Penicillium marneffei infection in humans and rodents, China. Emerg Infect Dis 17:209–214. [PubMed][CrossRef]
35. Anstead GM, Sutton DA, Graybill JR. 2012. Adiaspiromycosis causing respiratory failure and a review of human infections due to Emmonsia and Chrysosporium spp. J Clin Microbiol 50:1346–1354. [PubMed][CrossRef]
36. Emmons CW, Jellison WL. 1960. Emmonsia crescens sp. n. and adiaspiromycosis (haplomycosis) in mammals. Ann N Y Acad Sci 89:91–101. [PubMed][CrossRef]
37. Hubálek Z, Nesvadbová J, Halouzka J. 1998. Emmonsiosis of rodents in an agroecosystem. Med Mycol 36:387–390. [PubMed][CrossRef]
38. Pelegrín I, Ayats J, Xiol X, Cuenca-Estrella M, Jucglà A, Boluda S, Fernàndez-Sabé N, Rafecas A, Gudiol F, Cabellos C. 2011. Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review. Transpl Infect Dis 13:507–514. [PubMed][CrossRef]
39. Latgé JP. 1999. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350. [PubMed]
40. Malik KA, Sandhu GR. 1973. Decomposition of organic matter by fungi in saline soils. Mycopathol Mycol Appl 50:339–347. [PubMed][CrossRef]
41. Lewis RE, Cahyame-Zuniga L, Leventakos K, Chamilos G, Ben-Ami R, Tamboli P, Tarrand J, Bodey GP, Luna M, Kontoyiannis DP. 2013. Epidemiology and sites of involvement of invasive fungal infections in patients with haematological malignancies: A 20-year autopsy study. Mycoses 56:638–645. [PubMed][CrossRef]
42. Brakhage AA, Langfelder K. 2002. Menacing mold: The molecular biology of Aspergillus fumigatus. Annu Rev Microbiol 56:433–455. [PubMed][CrossRef]
43. Beffa T, Staib F, Lott Fischer J, Lyon PF, Gumowski P, Marfenina OE, Dunoyer-Geindre S, Georgen F, Roch-Susuki R, Gallaz L, Latgé JP. 1998. Mycological control and surveillance of biological waste and compost. Med Mycol 36(Suppl 1) :137–145. [PubMed]
44. Araujo R, Rodrigues AG. 2004. Variability of germinative potential among pathogenic species of Aspergillus. J Clin Microbiol 42:4335–4337. [PubMed][CrossRef]
45. Bhabhra R, Askew DS. 2005. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 43(Suppl 1) :S87–S93. [PubMed][CrossRef]
46. Bhabhra R, Miley MD, Mylonakis E, Boettner D, Fortwendel J, Panepinto JC, Postow M, Rhodes JC, Askew DS. 2004. Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect Immun 72:4731–4740. [PubMed][CrossRef]
47. Abad A, Fernández-Molina JV, Bikandi J, Ramírez A, Margareto J, Sendino J, Hernando FL, Pontón J, Garaizar J, Rementeria A. 2010. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol 27:155–182. [PubMed][CrossRef]
48. Askew DS. 2008. Aspergillus fumigatus: virulence genes in a street-smart mold. Curr Opin Microbiol 11:331–337. [PubMed][CrossRef]
49. Krishnan S, Manavathu EK, Chandrasekar PH. 2009. Aspergillus flavus: An emerging non-fumigatus Aspergillus species of significance. Mycoses 52:206–222. [PubMed][CrossRef]
50. García-Agudo L, Aznar-Marán P, Galán-Sánchez F, García-Martos P, Marín-Casanova P, Rodríguez-Iglesias M. 2011. Otomycosis due to filamentous fungi. Mycopathologia 172:307–310. [PubMed][CrossRef]
51. Vennewald I, Schönlebe J, Klemm E. 2003. Mycological and histological investigations in humans with middle ear infections. Mycoses 46:12–18. [PubMed][CrossRef]
52. Punia RS, Kundu R, Chander J, Arya SK, Handa U, Mohan H. 2014. Spectrum of fungal keratitis: clinicopathologic study of 44 cases. Int J Ophthalmol 7:114–117. [PubMed]
53. Osborne LE, Stein JM. 2007. Epidemiology of Fusarium head blight on small-grain cereals. Int J Food Microbiol 119:103–108. [PubMed][CrossRef]
54. Smiley RW, Gourlie JA, Easley SA, Patterson L-M, Whittake RG. 2005. Crop damage estimates for crown rot of wheat and barley in the Pacific Northwest. Plant Dis 89:595–604. [CrossRef]
55. Wu F, Groopman JD, Pestka JJ. 2014. Public health impacts of foodborne mycotoxins. Annu Rev Food Sci Technol 5:351–372. [PubMed][CrossRef]
56. Balajee SA, Borman AM, Brandt ME, Cano J, Cuenca-Estrella M, Dannaoui E, Guarro J, Haase G, Kibbler CC, Meyer W, O’Donnell K, Petti CA, Rodriguez-Tudela JL, Sutton D, Velegraki A, Wickes BL. 2009. Sequence-based identification of Aspergillus, Fusarium, and Mucorales species in the clinical mycology laboratory: where are we and where should we go from here? J Clin Microbiol 47:877–884. [PubMed][CrossRef]
57. Triest D, Stubbe D, De Cremer K, Piérard D, Normand AC, Piarroux R, Detandt M, Hendrickx M. 2015. Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of molds of the Fusarium genus. J Clin Microbiol 53:465–476. [PubMed][CrossRef]
58. Cuvelier I, Vogelaers D, Peleman R, Benoit D, Van Marck V, Offner F, Vandewoude K, Colardyn F. 1998. Two cases of disseminated mucormycosis in patients with hematological malignancies and literature review. Eur J Clin Microbiol Infect Dis 17:859–863. [PubMed][CrossRef]
59. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, Sein M, Sein T, Chiou CC, Chu JH, Kontoyiannis DP, Walsh TJ. 2005. Epidemiology and outcome of zygomycosis: A review of 929 reported cases. Clin Infect Dis 41:634–653. [PubMed][CrossRef]
60. Spellberg B, Edwards J Jr, Ibrahim A. 2005. Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev 18:556–569. [PubMed][CrossRef]
61. Pritchard RC, Muir DB. 1987. Black fungi: a survey of dematiaceous hyphomycetes from clinical specimens identified over a five year period in a reference laboratory. Pathology 19:281–284. [PubMed][CrossRef]
62. Revankar SG, Sutton DA. 2010. Melanized fungi in human disease. Clin Microbiol Rev 23:884–928. [PubMed][CrossRef]
63. Park BJ, Pappas PG, Wannemuehler KA, Alexander BD, Anaissie EJ, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S, Herwaldt L, Ito JI, Kauffman CA, Lyon GM, Marr KA, Morrison VA, Papanicolaou G, Patterson TF, Perl TM, Schuster MG, Walker R, Wingard JR, Walsh TJ, Kontoyiannis DP. 2011. Invasive non- Aspergillus mold infections in transplant recipients, United States, 2001–2006. Emerg Infect Dis 17:1855–1864. [PubMed][CrossRef]
64. Bonifaz A, Tirado-Sánchez A, Calderón L, Saúl A, Araiza J, Hernández M, González GM, Ponce RM. 2014. Mycetoma: experience of 482 cases in a single center in Mexico. PLoS Negl Trop Dis 8:e3102. doi:10.1371/journal.pntd.0003102 [PubMed][CrossRef]
65. Estrada R, Chavez-Lopez G, Estrada-Chavez G, Lopez-Martinez R, Welsh O. 2012. Eumycetoma. Clin Dermatol 30:389–396. [PubMed][CrossRef]
66. Revankar SG. 2007. Dematiaceous fungi. Mycoses 50:91–101. [PubMed][CrossRef]
67. Gade L, Grgurich DE, Kerkering TM, Brandt ME, Litvintseva AP. 2015. Utility of real-time PCR for detection of Exserohilum rostratum in body and tissue fluids during the multistate outbreak of fungal meningitis and other infections. J Clin Microbiol 53:618–625. [PubMed][CrossRef]
68. Brandt ME, Warnock DW. 2003. Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. J Chemother 15(Suppl 2) :36–47. [PubMed][CrossRef]
69. Roche M, Redmond RM, O’Neill S, Smyth E. 2005. A case of multiple cerebral abscesses due to infection with Cladophialophora bantiana. J Infect 51:e285–e288. [PubMed][CrossRef]
70. Shoham S, Pic-Aluas L, Taylor J, Cortez K, Rinaldi MG, Shea Y, Walsh TJ. 2008. Transplant-associated Ochroconis gallopava infections. Transpl Infect Dis 10:442–448. [PubMed][CrossRef]
71. Sutton DA, Slifkin M, Yakulis R, Rinaldi MG. 1998. U.S. case report of cerebral phaeohyphomycosis caused by Ramichloridium obovoideum ( R. mackenziei): criteria for identification, therapy, and review of other known dematiaceous neurotropic taxa. J Clin Microbiol 36:708–715. [PubMed]
72. Chang CL, Kim DS, Park DJ, Kim HJ, Lee CH, Shin JH. 2000. Acute cerebral phaeohyphomycosis due to Wangiella dermatitidis accompanied by cerebrospinal fluid eosinophilia. J Clin Microbiol 38:1965–1966. [PubMed]
73. Matsumoto T, Matsuda T, McGinnis MR, Ajello L. 1993. Clinical and mycological spectra of Wangiella dermatitidis infections. Mycoses 36:145–155. [PubMed][CrossRef]
74. Brown GD. 2011. Innate antifungal immunity: The key role of phagocytes. Annu Rev Immunol 29:1–21. [PubMed][CrossRef]
75. Schaffner A, Douglas H, Braude A. 1982. 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 69:617–631. [CrossRef]
76. Boyle KB, Stephens LR, Hawkins PT. 2012. Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus. Ann N Y Acad Sci 1273:68–73. [PubMed][CrossRef]
77. Duong M, Ouellet N, Simard M, Bergeron Y, Olivier M, Bergeron MG. 1998. Kinetic study of host defense and inflammatory response to Aspergillus fumigatus in steroid-induced immunosuppressed mice. J Infect Dis 178:1472–1482. [PubMed][CrossRef]
78. Ng TT, Robson GD, Denning DW. 1994. Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 140:2475–2479. [PubMed][CrossRef]
79. Romani L. 2011. Immunity to fungal infections. Nat Rev Immunol 11:275–288. [PubMed][CrossRef]
80. Braedel S, Radsak M, Einsele H, Latgé JP, Michan A, Loeffler J, Haddad Z, Grigoleit U, Schild H, Hebart H. 2004. Aspergillus fumigatus antigens activate innate immune cells via toll-like receptors 2 and 4. Br J Haematol 125:392–399. [PubMed][CrossRef]
81. Netea MG, Warris A, Van der Meer JW, Fenton MJ, Verver-Janssen TJ, Jacobs LE, Andresen T, Verweij PE, Kullberg BJ. 2003. Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis 188:320–326. [PubMed][CrossRef]
82. Osorio F, Reis e Sousa C. 2011. Myeloid C-type lectin receptors in pathogen recognition and host defense. Immunity 34:651–664. [PubMed][CrossRef]
83. Ramirez-Ortiz ZG, Means TK. 2012. The role of dendritic cells in the innate recognition of pathogenic fungi ( A. fumigatus, C. neoformans and C. albicans). Virulence 3:635–646. [PubMed][CrossRef]
84. Roy RM, Klein BS. 2012. Dendritic cells in antifungal immunity and vaccine design. Cell Host Microbe 11:436–446. [PubMed][CrossRef]
85. Espinosa V, Rivera A. 2012. Cytokines and the regulation of fungus-specific CD4 T cell differentiation. Cytokine 58:100–106. [PubMed][CrossRef]
86. Wüthrich M, Deepe GS Jr, Klein B. 2012. Adaptive immunity to fungi. Annu Rev Immunol 30:115–148. [PubMed][CrossRef]
87. Rivera A, Ro G, Van Epps HL, Simpson T, Leiner I, Sant’Angelo DB, Pamer EG. 2006. Innate immune activation and CD4+ T cell priming during respiratory fungal infection. Immunity 25:665–675. [PubMed][CrossRef]
88. Rivera A, Hohl TM, Collins N, Leiner I, Gallegos A, Saijo S, Coward JW, Iwakura Y, Pamer EG. 2011. Dectin-1 diversifies Aspergillus fumigatus-specific T cell responses by inhibiting T helper type 1 CD4 T cell differentiation. J Exp Med 208:369–381. [PubMed][CrossRef]
89. Wüthrich M, Gern B, Hung CY, Ersland K, Rocco N, Pick-Jacobs J, Galles K, Filutowicz H, Warner T, Evans M, Cole G, Klein B. 2011. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest 121:554–568. [PubMed][CrossRef]
90. Wüthrich M, Hung CY, Gern BH, Pick-Jacobs JC, Galles KJ, Filutowicz HI, Cole GT, Klein BS. 2011. A TCR transgenic mouse reactive with multiple systemic dimorphic fungi. J Immunol 187:1421–1431. [PubMed][CrossRef]
91. Cheson BD. 1995. Infectious and immunosuppressive complications of purine analog therapy. J Clin Oncol 13:2431–2448. [PubMed]
92. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP. 2008. Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin Proc 83:181–194. [PubMed][CrossRef]
93. Hernández-Santos N, Gaffen SL. 2012. Th17 cells in immunity to Candida albicans. Cell Host Microbe 11:425–435. [PubMed][CrossRef]
94. Edwards JE Jr. 2012. Fungal cell wall vaccines: An update. J Med Microbiol 61:895–903. [PubMed][CrossRef]
95. Torosantucci A, Chiani P, Bromuro C, De Bernardis F, Palma AS, Liu Y, Mignogna G, Maras B, Colone M, Stringaro A, Zamboni S, Feizi T, Cassone A. 2009. Protection by anti-beta-glucan antibodies is associated with restricted beta-1,3 glucan binding specificity and inhibition of fungal growth and adherence. PLoS One 4:e5392. doi:10.1371/journalpone.0005392
96. Guimarães AJ, Frases S, Gomez FJ, Zancopé-Oliveira RM, Nosanchuk JD. 2009. Monoclonal antibodies to heat shock protein 60 alter the pathogenesis of Histoplasma capsulatum. Infect Immun 77:1357–1367. [PubMed][CrossRef]
97. Buissa-Filho R, Puccia R, Marques AF, Pinto FA, Munoz JE, Nosanchuk JD, Travassos LR, Taborda CP. 2008. The monoclonal antibody against the major diagnostic antigen of Paracoccidioides brasiliensis mediates immune protection in infected BALB/c mice challenged intratracheally with the fungus. Infect Immun 76:3321–3328. [PubMed][CrossRef]
98. Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A, Janer M, Rodrigues SD, Li S, Hansen JA, Zhao LP, Aderem A, Boeckh M. 2008. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N Engl J Med 359:1766–1777. [PubMed][CrossRef]
99. Kesh S, Mensah NY, Peterlongo P, Jaffe D, Hsu K, Van Den Brink M, O’Reilly R, Pamer E, Satagopan J, Papanicolaou GA. 2005. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann N Y Acad Sci 1062:95–103. [PubMed][CrossRef]
100. Seo KW, Kim DH, Sohn SK, Lee NY, Chang HH, Kim SW, Jeon SB, Baek JH, Kim JG, Suh JS, Lee KB. 2005. Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation. Bone Marrow Transplant 36:1089–1095. [PubMed][CrossRef]
101. Sainz J, Hassan L, Perez E, Romero A, Moratalla A, López-Fernández E, Oyonarte S, Jurado M. 2007. Interleukin-10 promoter polymorphism as risk factor to develop invasive pulmonary aspergillosis. Immunol Lett 109:76–82. [PubMed][CrossRef]
102. Sainz J, Pérez E, Hassan L, Moratalla A, Romero A, Collado MD, Jurado M. 2007. Variable number of tandem repeats of TNF receptor type 2 promoter as genetic biomarker of susceptibility to develop invasive pulmonary aspergillosis. Hum Immunol 68:41–50. [PubMed][CrossRef]
103. Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhédin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S, Schwarzinger M. 2009. Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: A randomized, controlled trial. Clin Infect Dis 48:1042–1051. [PubMed][CrossRef]
104. Pagano L, Akova M, Dimopoulos G, Herbrecht R, Drgona L, Blijlevens N. 2011. Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. J Antimicrob Chemother 66(Suppl 1) :i5–i14. [PubMed][CrossRef]
105. Bodey GP. 1966. Infectious complications of acute leukemia. Med Times 94:1076–1085. [PubMed]
106. Portugal RD, Garnica M, Nucci M. 2009. Index to predict invasive mold infection in high-risk neutropenic patients based on the area over the neutrophil curve. J Clin Oncol 27:3849–3854. [PubMed][CrossRef]
107. Garcia-Vidal C, Upton A, Kirby KA, Marr KA. 2008. Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation. Clin Infect Dis 47:1041–1050. [PubMed][CrossRef]
108. Azie N, Neofytos D, Pfaller M, Meier-Kriesche HU, Quan SP, Horn D. 2012. The PATH (Prospective Antifungal Therapy) Alliance® registry and invasive fungal infections: update 2012. Diagn Microbiol Infect Dis 73:293–300. [PubMed][CrossRef]
109. Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, Pfaller M, Chang C, Webster K, Marr K. 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 48:265–273. [PubMed][CrossRef]
110. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, Ito J, Andes DR, Baddley JW, Brown JM, Brumble LM, Freifeld AG, Hadley S, Herwaldt LA, Kauffman CA, Knapp K, Lyon GM, Morrison VA, Papanicolaou G, Patterson TF, Perl TM, Schuster MG, Walker R, Wannemuehler KA, Wingard JR, Chiller TM, Pappas PG. 2010. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis 50:1091–1100. [PubMed][CrossRef]
111. Balajee SA, Kano R, Baddley JW, Moser SA, Marr KA, Alexander BD, Andes D, Kontoyiannis DP, Perrone G, Peterson S, Brandt ME, Pappas PG, Chiller T. 2009. Molecular identification of Aspergillus species collected for the Transplant-Associated Infection Surveillance Network. J Clin Microbiol 47:3138–3141. [PubMed][CrossRef]
112. Steinbach WJ, Marr KA, Anaissie EJ, Azie N, Quan SP, Meier-Kriesche HU, Apewokin S, Horn DL. 2012. Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry. J Infect 65:453–464. [PubMed][CrossRef]
113. Marty FM, Cosimi LA, Baden LR. 2004. Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants. N Engl J Med 350:950–952. [PubMed][CrossRef]
114. Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C, Safdar A, Kantarjian H, Champlin R, Walsh TJ, Raad II. 2005. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: A case-control observational study of 27 recent cases. J Infect Dis 191:1350–1360. [PubMed][CrossRef]
115. Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA, Freifeld A, Anaissie EJ, Brumble LM, Herwaldt L, Ito J, Kontoyiannis DP, Lyon GM, Marr KA, Morrison VA, Park BJ, Patterson TF, Perl TM, Oster RA, Schuster MG, Walker R, Walsh TJ, Wannemuehler KA, Chiller TM. 2010. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis 50:1101–1111. [PubMed][CrossRef]
116. Neofytos D, Fishman JA, Horn D, Anaissie E, Chang CH, Olyaei A, Pfaller M, Steinbach WJ, Webster KM, Marr KA. 2010. Epidemiology and outcome of invasive fungal infections in solid organ transplant recipients. Transpl Infect Dis 12:220–229. [PubMed][CrossRef]
117. Kauffman CA, Freifeld AG, Andes DR, Baddley JW, Herwaldt L, Walker RC, Alexander BD, Anaissie EJ, Benedict K, Ito JI, Knapp KM, Lyon GM, Marr KA, Morrison VA, Park BJ, Patterson TF, Schuster MG, Chiller TM, Pappas PG. 2014. Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET). Transpl Infect Dis 16:213–224. [PubMed][CrossRef]
118. Gomez CA, Singh N. 2013. Donor-derived filamentous fungal infections in solid organ transplant recipients. Curr Opin Infect Dis 26:309–316. [PubMed][CrossRef]
119. Altfeld M, Fadda L, Frleta D, Bhardwaj N. 2011. DCs and NK cells: critical effectors in the immune response to HIV-1. Nat Rev Immunol 11:176–186. [PubMed][CrossRef]
120. Armstrong-James D, Meintjes G, Brown GD. 2014. A neglected epidemic: fungal infections in HIV/AIDS. Trends Microbiol 22:120–127. [PubMed][CrossRef]
121. Holding KJ, Dworkin MS, Wan PC, Hanson DL, Klevens RM, Jones JL, Sullivan PS. 2000. Aspergillosis among people infected with human immunodeficiency virus: incidence and survival. Adult and Adolescent Spectrum of HIV Disease Project. Clin Infect Dis 31:1253–1257. [PubMed][CrossRef]
122. Lortholary O, Meyohas MC, Dupont B, Cadranel J, Salmon-Ceron D, Peyramond D, Simonin D. 1993. Invasive aspergillosis in patients with acquired immunodeficiency syndrome: report of 33 cases. French Cooperative Study Group on Aspergillosis in AIDS. Am J Med 95:177–187. [CrossRef]
123. Denning DW, Follansbee SE, Scolaro M, Norris S, Edelstein H, Stevens DA. 1991. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N Engl J Med 324:654–662. [PubMed][CrossRef]
124. Schneider E, Whitmore S, Glynn KM, Dominguez K, Mitsch A, McKenna MT; Centers fo Disease Control and Prevention (CDC). 2008. Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged <18 months and for HIV infection and AIDS among children aged 18 months to <13 years--United States, 2008. MMWR Recomm Rep 57:1–12. [PubMed]
125. Vanittanakom N, Cooper CR Jr, Fisher MC, Sirisanthana T. 2006. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev 19:95–110. [PubMed][CrossRef]
126. Kaplan JE, Masur H, Holmes KK; USPHS; Infectious Diseases Society of America. 2002. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep 51:1–52. [PubMed]
127. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf. Accessed March 1, 2015.
128. Jones JL, Fleming PL, Ciesielski CA, Hu DJ, Kaplan JE, Ward JW. 1995. Coccidioidomycosis among persons with AIDS in the United States. J Infect Dis 171:961–966. [PubMed][CrossRef]
129. Supparatpinyo K, Sirisanthana T. 1994. Disseminated Penicillium marneffei infection diagnosed on examination of a peripheral blood smear of a patient with human immunodeficiency virus infection. Clin Infect Dis 18:246–247. [PubMed][CrossRef]
130. Supparatpinyo K, Khamwan C, Baosoung V, Nelson KE, Sirisanthana T. 1994. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 344:110–113. [PubMed][CrossRef]
131. Alba-Loureiro TC, Munhoz CD, Martins JO, Cerchiaro GA, Scavone C, Curi R, Sannomiya P. 2007. Neutrophil function and metabolism in individuals with diabetes mellitus. Braz J Med Biol Res 40:1037–1044. [PubMed][CrossRef]
132. Foss NT, Foss-Freitas MC, Ferreira MA, Cardili RN, Barbosa CM, Foss MC. 2007. Impaired cytokine production by peripheral blood mononuclear cells in type 1 diabetic patients. Diabetes Metab 33:439–443. [PubMed][CrossRef]
133. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. 2012. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 54(Suppl 1) :S23–S34. [PubMed][CrossRef]
134. Artis WM, Fountain JA, Delcher HK, Jones HE. 1982. A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability. Diabetes 31:1109–1114. [PubMed][CrossRef]
135. Lanternier F, Cypowyj S, Picard C, Bustamante J, Lortholary O, Casanova JL, Puel A. 2013. Primary immunodeficiencies underlying fungal infections. Curr Opin Pediatr 25:736–747. [PubMed][CrossRef]
136. Blumental S, Mouy R, Mahlaoui N, Bougnoux ME, Debré M, Beauté J, Lortholary O, Blanche S, Fischer A. 2011. Invasive mold infections in chronic granulomatous disease: A 25-year retrospective survey. Clin Infect Dis 53:e159–e169. [PubMed][CrossRef]
137. Vinh DC, Sugui JA, Hsu AP, Freeman AF, Holland SM. 2010. Invasive fungal disease in autosomal-dominant hyper-IgE syndrome. J Allergy Clin Immunol 125:1389–1390. [PubMed][CrossRef]
138. Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J. 2004. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: A study of 81 patients from the French Neutropenia Register. Blood 103:4119–4125. [PubMed][CrossRef]
139. Fischer A, Lisowska-Grospierre B, Anderson DC, Springer TA. 1988. Leukocyte adhesion deficiency: molecular basis and functional consequences. Immunodefic Rev 1:39–54. [PubMed]
140. Kortsik C, Elmer A, Tamm I. 2003. Pleural effusion due to Histoplasma capsulatum and idiopathic CD4 lymphocytopenia. Respiration 70:118–122. [PubMed][CrossRef]
141. Vinh DC, Schwartz B, Hsu AP, Miranda DJ, Valdez PA, Fink D, Lau KP, Long-Priel D, Kuhns DB, Uzel G, Pittaluga S, Hoover S, Galgiani JN, Holland SM. 2011. Interleukin-12 receptor β1 deficiency predisposing to disseminated coccidioidomycosis. Clin Infect Dis 52:e99–e102. [PubMed][CrossRef]
142. Vinh DC, Masannat F, Dzioba RB, Galgiani JN, Holland SM. 2009. Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency. Clin Infect Dis 49:e62–e65. [PubMed][CrossRef]
143. Zerbe CS, Holland SM. 2005. Disseminated histoplasmosis in persons with interferon-gamma receptor 1 deficiency. Clin Infect Dis 41:e38–e41. [PubMed][CrossRef]
144. Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G. 2014. Invasive fungal infections in the ICU: how to approach, how to treat. Molecules 19:1085–1119. [PubMed][CrossRef]
145. Garnacho-Montero J, Olaechea P, Alvarez-Lerma F, Alvarez-Rocha L, Blanquer J, Galván B, Rodriguez A, Zaragoza R, Aguado JM, Mensa J, Solé A, Barberán J. 2013. Epidemiology, diagnosis and treatment of fungal respiratory infections in the critically ill patient. Rev Esp Quimioter 26:173–188. [PubMed]
146. He H, Jiang S, Zhang L, Sun B, Li F, Zhan Q, Wang C. 2014. Aspergillus tracheobronchitis in critically ill patients with chronic obstructive pulmonary diseases. Mycoses 57:473–482. [PubMed][CrossRef]
147. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG, Infectious Diseases Society of America, American Thoracic Society. 2007. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(Suppl 2) :S27–S72. [PubMed][CrossRef]
148. Hummel M, Rudert S, Hof H, Hehlmann R, Buchheidt D. 2008. Diagnostic yield of bronchoscopy with bronchoalveolar lavage in febrile patients with hematologic malignancies and pulmonary infiltrates. Ann Hematol 87:291–297. [PubMed][CrossRef]
149. Maeda H, Ishida N. 1967. Specificity of binding of hexopyranosyl polysaccharides with fluorescent brightener. J Biochem 62:276–278. [PubMed]
150. Sangoi AR, Rogers WM, Longacre TA, Montoya JG, Baron EJ, Banaei N. 2009. Challenges and pitfalls of morphologic identification of fungal infections in histologic and cytologic specimens: A ten-year retrospective review at a single institution. Am J Clin Pathol 131:364–375. [PubMed][CrossRef]
151. McGowan KL. 2011. Specimen Collection, Transport, and Processing: Mycology. In Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW (ed), Manual of Clinical Microbiology, 10th ed, vol 2. ASM Press, Washington, DC. [CrossRef]
152. Levine SJ. 1992. An approach to the diagnosis of pulmonary infections in immunosuppressed patients. Semin Respir Infect 7:81–95. [PubMed]
153. Guimãraes AJ, Nosanchuk JD, Zancopé-Oliveira RM. 2006. Diagnosis of histoplasmosis. Braz J Microbiol 37:1–13. [PubMed][CrossRef]
154. Pappagianis D, Zimmer BL. 1990. Serology of coccidioidomycosis. Clin Microbiol Rev 3:247–268. [PubMed]
155. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C, Walsh TJ. 2004. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis 190:641–649. [PubMed][CrossRef]
156. Machetti M, Zotti M, Veroni L, Mordini N, Van Lint MT, Bacigalupo A, Paola D, Viscoli C. 2000. Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole. Transpl Infect Dis 2:140–144. [PubMed][CrossRef]
157. Kono Y, Tsushima K, Yamaguchi K, Kurita N, Soeda S, Fujiwara A, Sugiyama S, Togashi Y, Kasagi S, To M, To Y, Setoguchi Y. 2013. The utility of galactomannan antigen in the bronchial washing and serum for diagnosing pulmonary aspergillosis. Respir Med 107:1094–1100. [PubMed][CrossRef]
158. Bio-Rad. 2009. Platelia™ Aspergillus. EIA Package Insert, Marnes La Coquette, France.
159. Maertens J, Maertens V, Theunissen K, Meersseman W, Meersseman P, Meers S, Verbeken E, Verhoef G, Van Eldere J, Lagrou K. 2009. Bronchoalveolar lavage fluid galactomannan for the diagnosis of invasive pulmonary aspergillosis in patients with hematologic diseases. Clin Infect Dis 49:1688–1693. [PubMed][CrossRef]
160. Pasqualotto AC, Xavier MO, Sánchez LB, de Oliveira Costa CD, Schio SM, Camargo SM, Camargo JJ, Sukiennik TC, Severo LC. 2010. Diagnosis of invasive aspergillosis in lung transplant recipients by detection of galactomannan in the bronchoalveolar lavage fluid. Transplantation 90:306–311. [PubMed][CrossRef]
161. Maertens J, Theunissen K, Verhoef G, Verschakelen J, Lagrou K, Verbeken E, Wilmer A, Verhaegen J, Boogaerts M, Van Eldere J. 2005. Galactomannan and computed tomography-based preemptive antifungal therapy in neutropenic patients at high risk for invasive fungal infection: A prospective feasibility study. Clin Infect Dis 41:1242–1250. [PubMed][CrossRef]
162. Husain S, Kwak EJ, Obman A, Wagener MM, Kusne S, Stout JE, McCurry KR, Singh N. 2004. Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant 4:796–802. [PubMed][CrossRef]
163. Schelenz S, Barnes RA, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, Denning DW; British Society for Medical Mycology. 2015. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis 15:461–474. [PubMed][CrossRef]
164. Pfeiffer CD, Fine JP, Safdar N. 2006. Diagnosis of invasive aspergillosis using a galactomannan assay: A meta-analysis. Clin Infect Dis 42:1417–1427. [PubMed][CrossRef]
165. Lamoth F, Cruciani M, Mengoli C, Castagnola E, Lortholary O, Richardson M, Marchetti O. 2012. β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: A systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3). Clin Infect Dis 54:633–643. [PubMed][CrossRef]
166. Mennink-Kersten MA, Donnelly JP, Verweij PE. 2004. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect Dis 4:349–357. [PubMed][CrossRef]
167. Guigue N, Menotti J, Ribaud P. 2013. False positive galactomannan test after ice-pop ingestion. N Engl J Med 369:97–98. [PubMed][CrossRef]
168. Fisher CE, Stevens AM, Leisenring W, Pergam SA, Boeckh M, Hohl TM. 2014. Independent contribution of bronchoalveolar lavage and serum galactomannan in the diagnosis of invasive pulmonary aspergillosis. Transpl Infect Dis 16:505–510. [PubMed][CrossRef]
169. Avni T, Levy I, Sprecher H, Yahav D, Leibovici L, Paul M. 2012. Diagnostic accuracy of PCR alone compared to galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis: A systematic review. J Clin Microbiol 50:3652–3658. [PubMed][CrossRef]
170. Zou M, Tang L, Zhao S, Zhao Z, Chen L, Chen P, Huang Z, Li J, Chen L, Fan X. 2012. Systematic review and meta-analysis of detecting galactomannan in bronchoalveolar lavage fluid for diagnosing invasive aspergillosis. PLoS One 7:e43347. doi:10.1371/journal.pone.0043347 [CrossRef]
171. Heng SC, Morrissey O, Chen SC, Thursky K, Manser RL, Nation RL, Kong DC, Slavin M. 2013. Utility of bronchoalveolar lavage fluid galactomannan alone or in combination with PCR for the diagnosis of invasive aspergillosis in adult hematology patients: A systematic review and meta-analysis. Crit Rev Microbiol 41:124–134. [PubMed][CrossRef]
172. Aguado JM, Vázquez L, Fernández-Ruiz M, Villaescusa T, Ruiz-Camps I, Barba P, Silva JT, Batlle M, Solano C, Gallardo D, Heras I, Polo M, Varela R, Vallejo C, Olave T, López-Jiménez J, Rovira M, Parody R, Cuenca-Estrella M; PCRAGA Study Group; Spanish Stem Cell Transplantation Group; Study Group of Medical Mycology of the Spanish Society of Clinical Microbiology and Infectious Diseases; Spanish Network for Research in Infectious Diseases. 2015. Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: A randomized controlled trial. Clin Infect Dis 60:405–414. [PubMed][CrossRef]
173. Associates of Cape Cod Inc. 2011. Assay for (1→3)-β-D-glucan in serum: Fungitell instructions for use, Falmouth, MA.
174. Marty FM, Koo S. 2009. Role of (1→3)-beta-D-glucan in the diagnosis of invasive aspergillosis. Med Mycol 47(Suppl 1) :S233–S240. [PubMed][CrossRef]
175. Onishi A, Sugiyama D, Kogata Y, Saegusa J, Sugimoto T, Kawano S, Morinobu A, Nishimura K, Kumagai S. 2012. Diagnostic accuracy of serum 1,3-β-D-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol 50:7–15. [PubMed][CrossRef]
176. Litvintseva AP, Lindsley MD, Gade L, Smith R, Chiller T, Lyons JL, Thakur KT, Zhang SX, Grgurich DE, Kerkering TM, Brandt ME, Park BJ. 2013. Utility of (1-3)-β-D-glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of fungal meningitis and other infections. Clin Infect Dis 58:622–630. [PubMed][CrossRef]
177. Lyons JL, Roos KL, Marr KA, Neumann H, Trivedi JB, Kimbrough DJ, Steiner L, Thakur KT, Harrison DM, Zhang SX. 2013. Cerebrospinal fluid (1,3)-β-D-glucan detection as an aid for diagnosis of iatrogenic fungal meningitis. J Clin Microbiol 51:1285–1287. [PubMed][CrossRef]
178. Egan L, Connolly P, Wheat LJ, Fuller D, Dais TE, Knox KS, Hage CA. 2008. Histoplasmosis as a cause for a positive Fungitell (1 → 3)-beta-D-glucan test. Med Mycol 46:93–95. [PubMed][CrossRef]
179. Thompson GR III, Bays DJ, Johnson SM, Cohen SH, Pappagianis D, Finkelman MA. 2012. Serum (1→3)-β-D-glucan measurement in coccidioidomycosis. J Clin Microbiol 50:3060–3062. [PubMed][CrossRef]
180. Hanson KE, Pfeiffer CD, Lease ED, Balch AH, Zaas AK, Perfect JR, Alexander BD. 2012. β-D-glucan surveillance with preemptive anidulafungin for invasive candidiasis in intensive care unit patients: A randomized pilot study. PLoS One 7:e42282. doi:10.1371/journal.pone.0042282 [CrossRef]
181. Ikemura K, Ikegami K, Shimazu T, Yoshioka T, Sugimoto T. 1989. False-positive result in Limulus test caused by Limulus amebocyte lysate-reactive material in immunoglobulin products. J Clin Microbiol 27:1965–1968. [PubMed]
182. Kanamori H, Kanemitsu K, Miyasaka T, Ameku K, Endo S, Aoyagi T, Inden K, Hatta M, Yamamoto N, Kunishima H, Yano H, Kaku K, Hirakata Y, Kaku M. 2009. Measurement of (1-3)-beta-D-glucan derived from different gauze types. Tohoku J Exp Med 217:117–121. [PubMed][CrossRef]
183. Alexander BD, Smith PB, Davis RD, Perfect JR, Reller LB. 2010. The (1,3){beta}-D-glucan test as an aid to early diagnosis of invasive fungal infections following lung transplantation. J Clin Microbiol 48:4083–4088. [PubMed][CrossRef]
184. Penack O, Schwartz S, Thiel E, Wolfgang Blau I. 2004. Lack of evidence that false-positive Aspergillus galactomannan antigen test results are due to treatment with piperacillin-tazobactam. Clin Infect Dis 39:1401–1402, author reply 1402–1403. [PubMed][CrossRef]
185. Smith PB, Benjamin DK Jr, Alexander BD, Johnson MD, Finkelman MA, Steinbach WJ. 2007. Quantification of 1,3-beta-D-glucan levels in children: preliminary data for diagnostic use of the beta-glucan assay in a pediatric setting. Clin Vaccine Immunol 14:924–925. [PubMed][CrossRef]
186. IMMY. 2011. ALPHA Histoplasma EIA Test Kit: for the detection of histoplasma. Antigen, Norman, OK.
187. Zhang X, Gibson B Jr, Daly TM. 2013. Evaluation of commercially available reagents for diagnosis of histoplasmosis infection in immunocompromised patients. J Clin Microbiol 51:4095–4101. [PubMed][CrossRef]
188. Wheat LJ, Kohler RB, Tewari RP, Garten M, French ML. 1989. Significance of Histoplasma antigen in the cerebrospinal fluid of patients with meningitis. Arch Intern Med 149:302–304. [PubMed][CrossRef]
189. Hage CA, Davis TE, Fuller D, Egan L, Witt JR III, Wheat LJ, Knox KS. 2010. Diagnosis of histoplasmosis by antigen detection in BAL fluid. Chest 137:623–628. [PubMed][CrossRef]
190. Riddell J IV, Kauffman CA, Smith JA, Assi M, Blue S, Buitrago MI, Deresinski S, Wright PW, Drevets DA, Norris SA, Vikram HR, Carson PJ, Vergidis P, Carpenter J, Seidenfeld SM, Wheat LJ. 2014. Histoplasma capsulatum endocarditis: multicenter case series with review of current diagnostic techniques and treatment. Medicine (Baltimore) 93:186–193. [PubMed][CrossRef]
191. Assi M, Martin S, Wheat LJ, Hage C, Freifeld A, Avery R, Baddley JW, Vergidis P, Miller R, Andes D, Young JA, Hammoud K, Huprikar S, McKinsey D, Myint T, Garcia-Diaz J, Esguerra E, Kwak EJ, Morris M, Mullane KM, Prakash V, Burdette SD, Sandid M, Dickter J, Ostrander D, Antoun SA, Kaul DR. 2013. Histoplasmosis after solid organ transplant. Clin Infect Dis 57:1542–1549. [PubMed][CrossRef]
192. Kuberski T, Myers R, Wheat LJ, Durkin M, Connolly P, Kubak BM, Bruckner D, Pegues D. 2007. Diagnosis of coccidioidomycosis by antigen detection using cross-reaction with a Histoplasma antigen. Clin Infect Dis 44:e50–e54. [PubMed][CrossRef]
193. Wheat J, Wheat H, Connolly P, Kleiman M, Supparatpinyo K, Nelson K, Bradsher R, Restrepo A. 1997. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis 24:1169–1171. [PubMed][CrossRef]
194. Connolly P, Hage CA, Bariola JR, Bensadoun E, Rodgers M, Bradsher RW Jr, Wheat LJ. 2012. Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay. Clin Vaccine Immunol 19:53–56. [PubMed][CrossRef]
195. Durkin M, Connolly P, Kuberski T, Myers R, Kubak BM, Bruckner D, Pegues D, Wheat LJ. 2008. Diagnosis of coccidioidomycosis with use of the Coccidioides antigen enzyme immunoassay. Clin Infect Dis 47:e69–e73. [PubMed][CrossRef]
196. Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, Garey KW, Alangaden GJ, Vazquez JA, Groeger JS, Judson MA, Vinagre YM, Heard SO, Zervou FN, Zacharioudakis IM, Kontoyiannis DP, Pappas PG. 2015. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: A clinical trial. Clin Infect Dis 60:892–899. [PubMed][CrossRef]
197. Mengoli C, Cruciani M, Barnes RA, Loeffler J, Donnelly JP. 2009. Use of PCR for diagnosis of invasive aspergillosis: systematic review and meta-analysis. Lancet Infect Dis 9:89–96. [CrossRef]
198. Loeffler J, Hebart H, Brauchle U, Schumacher U, Einsele H. 2000. Comparison between plasma and whole blood specimens for detection of Aspergillus DNA by PCR. J Clin Microbiol 38:3830–3833. [PubMed]
199. Hoenigl M, Prattes J, Spiess B, Wagner J, Prueller F, Raggam RB, Posch V, Duettmann W, Hoenigl K, Wölfler A, Koidl C, Buzina W, Reinwald M, Thornton CR, Krause R, Buchheidt D. 2014. Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device, conventional culture, and PCR tests with bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. J Clin Microbiol 52:2039–2045. [PubMed][CrossRef]
200. Luong ML, Clancy CJ, Vadnerkar A, Kwak EJ, Silveira FP, Wissel MC, Grantham KJ, Shields RK, Crespo M, Pilewski J, Toyoda Y, Kleiboeker SB, Pakstis D, Reddy SK, Walsh TJ, Nguyen MH. 2011. Comparison of an Aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalvelolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis 52:1218–1226. [PubMed][CrossRef]
201. Zhao Y, Park S, Warn P, Shrief R, Harrison E, Perlin DS. 2010. Detection of Aspergillus fumigatus in a rat model of invasive pulmonary aspergillosis by real-time nucleic acid sequence-based amplification. J Clin Microbiol 48:1378–1383. [PubMed][CrossRef]
202. Harrison E, Stalhberger T, Whelan R, Sugrue M, Wingard JR, Alexander BD, Follett SA, Bowyer P, Denning DW. 2010. Aspergillus DNA contamination in blood collection tubes. Diagn Microbiol Infect Dis 67:392–394. [PubMed][CrossRef]
203. Loeffler J, Hebart H, Bialek R, Hagmeyer L, Schmidt D, Serey FP, Hartmann M, Eucker J, Einsele H. 1999. Contaminations occurring in fungal PCR assays. J Clin Microbiol 37:1200–1202. [PubMed]
204. Muñoz-Cadavid C, Rudd S, Zaki SR, Patel M, Moser SA, Brandt ME, Gómez BL. 2010. Improving molecular detection of fungal DNA in formalin-fixed paraffin-embedded tissues: comparison of five tissue DNA extraction methods using panfungal PCR. J Clin Microbiol 48:2147–2153. [PubMed][CrossRef]
205. Lau A, Chen S, Sorrell T, Carter D, Malik R, Martin P, Halliday C. 2007. Development and clinical application of a panfungal PCR assay to detect and identify fungal DNA in tissue specimens. J Clin Microbiol 45:380–385. [PubMed][CrossRef]
206. Buitrago MJ, Aguado JM, Ballen A, Bernal-Martinez L, Prieto M, Garcia-Reyne A, Garcia-Rodriguez J, Rodriguez-Tudela JL, Cuenca-Estrella M. 2013. Efficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease. Clin Microbiol Infect 19:E271–E277. [PubMed][CrossRef]
207. Rickerts V, Khot PD, Myerson D, Ko DL, Lambrecht E, Fredricks DN. 2011. Comparison of quantitative real time PCR with sequencing and ribosomal RNA-FISH for the identification of fungi in formalin fixed, paraffin-embedded tissue specimens. BMC Infect Dis 11:202. doi:10.1186/1471-2334-11-202 [PubMed][CrossRef]
208. Huttner A, Emonet S, Harbarth S, Renzi G, Kaiser L, Schrenzel J. 2014. Polymerase-chain reaction/electrospray ionization-mass spectrometry for the detection of bacteria and fungi in bronchoalveolar lavage fluids: A prospective observational study. Clin Microbiol Infect 20:O1059–O1066. [PubMed][CrossRef]
209. Babady NE, Buckwalter SP, Hall L, Le Febre KM, Binnicker MJ, Wengenack NL. 2011. Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol 49:3204–3208. [PubMed][CrossRef]
210. Simner PJ, Uhl JR, Hall L, Weber MM, Walchak RC, Buckwalter S, Wengenack NL. 2013. Broad-range direct detection and identification of fungi by use of the PLEX-ID PCR-electrospray ionization mass spectrometry (ESI-MS) system. J Clin Microbiol 51:1699–1706. [PubMed][CrossRef]
211. Springer J, Morton CO, Perry M, Heinz WJ, Paholcsek M, Alzheimer M, Rogers TR, Barnes RA, Einsele H, Loeffler J, White PL. 2013. Multicenter comparison of serum and whole-blood specimens for detection of Aspergillus DNA in high-risk hematological patients. J Clin Microbiol 51:1445–1450. [PubMed][CrossRef]
212. White PL, Bretagne S, Klingspor L, Melchers WJ, McCulloch E, Schulz B, Finnstrom N, Mengoli C, Barnes RA, Donnelly JP, Loeffler J; European Aspergillus PCR Initiative. 2010. Aspergillus PCR: one step closer to standardization. J Clin Microbiol 48:1231–1240. [PubMed][CrossRef]
213. White PL, Perry MD, Loeffler J, Melchers W, Klingspor L, Bretagne S, McCulloch E, Cuenca-Estrella M, Finnstrom N, Donnelly JP, Barnes RA. 2010. Critical stages of extracting DNA from Aspergillus fumigatus in whole-blood specimens. J Clin Microbiol 48:3753–3755. [PubMed][CrossRef]
214. Lau AF, Drake SK, Calhoun LB, Henderson CM, Zelazny AM. 2013. Development of a clinically comprehensive database and a simple procedure for identification of molds from solid media by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 51:828–834. [PubMed][CrossRef]
215. Koo STH, Rearden P, Comolli J, Baden LR, Marty FM. An Aspergillus fumigatus (AF)- Specific Breath Volatile Organic Compound (VOC) Profile is Diagnostic of Invasive Aspergillosis (IA). 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy. Denver, CO.
216. Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, Solary E, Piard F, Petrella T, Bonnin A, Couillault G, Dumas M, Guy H. 1997. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol 15:139–147. [PubMed]
217. Greene RE, Schlamm HT, Oestmann JW, Stark P, Durand C, Lortholary O, Wingard JR, Herbrecht R, Ribaud P, Patterson TF, Troke PF, Denning DW, Bennett JE, de Pauw BE, Rubin RH. 2007. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 44:373–379. [PubMed][CrossRef]
218. Brodoefel H, Vogel M, Hebart H, Einsele H, Vonthein R, Claussen C, Horger M. 2006. Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. AJR Am J Roentgenol 187:404–413. [PubMed][CrossRef]
219. Georgopapadakou NH, Walsh TJ. 1996. Antifungal agents: chemotherapeutic targets and immunologic strategies. Antimicrob Agents Chemother 40:279–291. [PubMed]
220. Pfaller MA, Diekema DJ. 2004. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J Clin Microbiol 42:4419–4431. [PubMed][CrossRef]
221. Clinical and Laboratory Standards Institute. 2008. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. Approved Standard M38-A2. Clinical and Laboratory Standards Institute, Wayne, PA.
222. Meletiadis J, Antachopoulos C, Stergiopoulou T, Pournaras S, Roilides E, Walsh TJ. 2007. Differential fungicidal activities of amphotericin B and voriconazole against Aspergillus species determined by microbroth methodology. Antimicrob Agents Chemother 51:3329–3337. [PubMed][CrossRef]
223. Krishnan-Natesan S, Manavathu EK, Alangaden GJ, Chandrasekar PH. 2009. A comparison of the fungicidal activity of amphotericin B and posaconazole against zygomycetes in vitro. Diagn Microbiol Infect Dis 63:361–364. [PubMed][CrossRef]
224. Lass-Flörl C. 2011. Triazole antifungal agents in invasive fungal infections: A comparative review. Drugs 71:2405–2419. [PubMed][CrossRef]
225. Almyroudis NG, Sutton DA, Fothergill AW, Rinaldi MG, Kusne S. 2007. In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional and new antifungal agents. Antimicrob Agents Chemother 51:2587–2590. [PubMed][CrossRef]
226. Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope W, Howard SJ, EUCAST. A. 2014. EUCAST Method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds version 9.2. European Society of Clinical Microbiology and Infectious Diseases. http://www.eucast.org/ast_of_fungi/methodsinantifungalsusceptibilitytesting/susceptibility_testing_of_moulds/ Accessed February 27, 2015.
227. Simjee S, Silley P, Werling HO, Bywater R. 2008. Potential confusion regarding the term ‘resistance’ in epidemiological surveys. J Antimicrob Chemother 61:228–229. [PubMed][CrossRef]
228. Pfaller MA, Diekema DJ. 2012. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol 50:2846–2856. [PubMed][CrossRef]
229. Arendrup MC, Kahlmeter G, Rodriguez-Tudela JL, Donnelly JP. 2009. Breakpoints for susceptibility testing should not divide wild-type distributions of important target species. Antimicrob Agents Chemother 53:1628–1629. [PubMed][CrossRef]
230. Turnidge J, Kahlmeter G, Kronvall G. 2006. Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values. Clin Microbiol Infect 12:418–425. [PubMed][CrossRef]
231. De Carolis E, Vella A, Florio AR, Posteraro P, Perlin DS, Sanguinetti M, Posteraro B. 2012. Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry for caspofungin susceptibility testing of Candida and Aspergillus species. J Clin Microbiol 50:2479–2483. [PubMed][CrossRef]
232. Bader O, Weig M, Reichard U, Lugert R, Kuhns M, Christner M, Held J, Peter S, Schumacher U, Buchheidt D, Tintelnot K, Groβ U, MykoLabNet-D Partners. 2013. cyp51A-Based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. Antimicrob Agents Chemother 57:3513–3517. [PubMed][CrossRef]
233. Astellas Pharma US Inc. 2014. Mycamine (micafungin), Northbrook, IL.
234. Merck & Co. Inc. 2014. Noxafil (posaconazole). Whitehouse Station, NJ.
235. Hebart H, Klingspor L, Klingebiel T, Loeffler J, Tollemar J, Ljungman P, Wandt H, Schaefer-Eckart K, Dornbusch HJ, Meisner C, Engel C, Stenger N, Mayer T, Ringden O, Einsele H. 2009. A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT. Bone Marrow Transplant 43:553–561. [PubMed][CrossRef]
236. Rogers TR, Morton CO, Springer J, Conneally E, Heinz W, Kenny C, Frost S, Einsele H, Loeffler J. 2013. Combined real-time PCR and galactomannan surveillance improves diagnosis of invasive aspergillosis in high risk patients with haematological malignancies. Br J Haematol 161:517–524. [PubMed][CrossRef]
237. Morrissey CO, Chen SC, Sorrell TC, Milliken S, Bardy PG, Bradstock KF, Szer J, Halliday CL, Gilroy NM, Moore J, Schwarer AP, Guy S, Bajel A, Tramontana AR, Spelman T, Slavin MA; Australasian Leukaemia Lymphoma Group; Australia and New Zealand Mycology Interest Group. 2013. Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: A randomised controlled trial. Lancet Infect Dis 13:519–528. [PubMed][CrossRef]
238. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. 2007. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis 44:531–540. [PubMed][CrossRef]
239. Nivoix Y, Velten M, Letscher-Bru V, Moghaddam A, Natarajan-Amé S, Fohrer C, Lioure B, Bilger K, Lutun P, Marcellin L, Launoy A, Freys G, Bergerat JP, Herbrecht R. 2008. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin Infect Dis 47:1176–1184. [PubMed][CrossRef]
240. Hammond SP, Baden LR, Marty FM. 2011. Mortality in hematologic malignancy and hematopoietic stem cell transplant patients with mucormycosis, 2001 to 2009. Antimicrob Agents Chemother 55:5018–5021. [PubMed][CrossRef]
241. Campo M, Lewis RE, Kontoyiannis DP. 2010. Invasive fusariosis in patients with hematologic malignancies at a cancer center: 1998–2009. J Infect 60:331–337. [PubMed][CrossRef]
242. Nucci M, Anaissie EJ, Queiroz-Telles F, Martins CA, Trabasso P, Solza C, Mangini C, Simões BP, Colombo AL, Vaz J, Levy CE, Costa S, Moreira VA, Oliveira JS, Paraguay N, Duboc G, Voltarelli JC, Maiolino A, Pasquini R, Souza CA. 2003. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer 98:315–319. [PubMed][CrossRef]
243. Husain S, Muñoz P, Forrest G, Alexander BD, Somani J, Brennan K, Wagener MM, Singh N. 2005. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis 40:89–99. [PubMed][CrossRef]
244. Heng SC, Slavin MA, Chen SC, Heath CH, Nguyen Q, Billah B, Nation RL, Kong DC. 2012. Hospital costs, length of stay and mortality attributable to invasive scedosporiosis in haematology patients. J Antimicrob Chemother 67:2274–2282. [PubMed][CrossRef]
245. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. 2011. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:427–431. [PubMed][CrossRef]
246. Morrissey CO, Gilroy NM, Macesic N, Walker P, Ananda-Rajah M, May M, Heath CH, Grigg A, Bardy PG, Kwan J, Kirsa SW, Slavin M, Gottlieb T, Chen S. 2014. Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014. Intern Med J 44:1298–1314. [PubMed][CrossRef]
247. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF;Infectious Diseases Society of America. 2008. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46:327–360. [PubMed][CrossRef]
248. Perfect JR, Marr KA, Walsh TJ, Greenberg RN, DuPont B, de la Torre-Cisneros J, Just-Nübling G, Schlamm HT, Lutsar I, Espinel-Ingroff A, Johnson E. 2003. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 36:1122–1131. [PubMed][CrossRef]
249. Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, Buchanan W, Milanovich J, Sutton DA, Fothergill A, Rinaldi MG, Shea YR, Zaoutis T, Kottilil S, Walsh TJ. 2008. Infections caused by Scedosporium spp. Clin Microbiol Rev 21:157–197. [PubMed][CrossRef]
250. Spellberg B, Walsh TJ, Kontoyiannis DP, Edwards J Jr, Ibrahim AS. 2009. Recent advances in the management of mucormycosis: from bench to bedside. Clin Infect Dis 48:1743–1751. [PubMed][CrossRef]
251. Greenberg RN, Mullane K, van Burik JA, Raad I, Abzug MJ, Anstead G, Herbrecht R, Langston A, Marr KA, Schiller G, Schuster M, Wingard JR, Gonzalez CE, Revankar SG, Corcoran G, Kryscio RJ, Hare R. 2006. Posaconazole as salvage therapy for zygomycosis. Antimicrob Agents Chemother 50:126–133. [PubMed][CrossRef]
252. Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, Greene RE, Hachem R, Hadley S, Herbrecht R, Langston A, Louie A, Ribaud P, Segal BH, Stevens DA, van Burik JA, White CS, Corcoran G, Gogate J, Krishna G, Pedicone L, Hardalo C, Perfect JR. 2007. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An externally controlled trial. Clin Infect Dis 44:2–12. [PubMed][CrossRef]
253. van Burik JA, Hare RS, Solomon HF, Corrado ML, Kontoyiannis DP. 2006. Posaconazole is effective as salvage therapy in zygomycosis: A retrospective summary of 91 cases. Clin Infect Dis 42:e61–e65. [PubMed][CrossRef]
254. Galgiani JN, Ampel NM, Blair JE, Catanzaro A, Johnson RH, Stevens DA, Williams PL; Infectious Diseases Society of America. 2005. Coccidioidomycosis. Clin Infect Dis 41:1217–1223. [PubMed][CrossRef]
255. Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, Kauffman CA; Infectious Diseases Society of America. 2007. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis 45:807–825. [PubMed][CrossRef]
256. Weber DJ, Peppercorn A, Miller MB, Sickbert-Benett E, Rutala WA. 2009. Preventing healthcare-associated Aspergillus infections: review of recent CDC/HICPAC recommendations. Med Mycol 47(Suppl 1) :S199–S209. [PubMed][CrossRef]
257. Abdul Salam ZH, Karlin RB, Ling ML, Yang KS. 2010. The impact of portable high-efficiency particulate air filters on the incidence of invasive aspergillosis in a large acute tertiary-care hospital. Am J Infect Control 38:e1–e7. [PubMed][CrossRef]
258. Anaissie EJ, Stratton SL, Dignani MC, Lee CK, Summerbell RC, Rex JH, Monson TP, Walsh TJ. 2003. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: A 3-year prospective study and clinical implications for patients with hematologic malignancies. Blood 101:2542–2546. [PubMed][CrossRef]
259. Lass-Florl C, Rath P, Niederwieser D, Kofler G, Würzner R, Krezy A, Dierich MP. 2000. Aspergillusterreus infections in haematological malignancies: molecular epidemiology suggests association with in-hospital plants. J Hosp Infect 46:31–35. [PubMed][CrossRef]
260. Rammaert B, Lanternier F, Zahar JR, Dannaoui E, Bougnoux ME, Lecuit M, Lortholary O. 2012. Healthcare-associated mucormycosis. Clin Infect Dis 54(Suppl 1) :S44–S54. [PubMed][CrossRef]
261. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ; Center fpr International Blood and Marrow Research; National Marrow Donor Program; European Blood and Marrow Transplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention. 2009. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: A global perspective. Biol Blood Marrow Transplant 15:1143–1238. [PubMed][CrossRef]
262. Herbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher-Bru V. 2012. Risk stratification for invasive aspergillosis in immunocompromised patients. Ann N Y Acad Sci 1272:23–30. [PubMed][CrossRef]
263. Espinel-Ingroff A, Chakrabarti A, Chowdhary A, Cordoba S, Dannaoui E, Dufresne P, Fothergill A, Ghannoum M, Gonzalez GM, Guarro J, Kidd S, Lass-Flörl C, Meis JF, Pelaez T, Tortorano AM, Turnidge J. 2015. Multicenter evaluation of MIC distributions for epidemiologic cutoff value definition to detect amphotericin B, posaconazole, and itraconazole resistance among the most clinically relevant species of Mucorales. Antimicrob Agents Chemother 59:1745–1750. [PubMed][CrossRef]
264. Espinel-Ingroff A, Chowdhary A, Gonzalez GM, Lass-Flörl C, Martin-Mazuelos E, Meis J, Peláez T, Pfaller MA, Turnidge J. 2013. Multicenter study of isavuconazole MIC distributions and epidemiological cutoff values for Aspergillus spp. for the CLSI M38-A2 broth microdilution method. Antimicrob Agents Chemother 57:3823–3828. [PubMed][CrossRef]
265. Espinel-Ingroff A, Cuenca-Estrella M, Fothergill A, Fuller J, Ghannoum M, Johnson E, Peláez T, Pfaller MA, Turnidge J. 2011. Wild-type MIC distributions and epidemiological cutoff values for amphotericin B and Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). Antimicrob Agents Chemother 55:5150–5154. [PubMed][CrossRef]
266. Espinel-Ingroff A, Diekema DJ, Fothergill A, Johnson E, Peláez T, Pfaller MA, Rinaldi MG, Canton E, Turnidge J. 2010. Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). J Clin Microbiol 48:3251–3257. [PubMed][CrossRef]
267. Espinel-Ingroff A, Fothergill A, Fuller J, Johnson E, Peláez T, Turnidge J. 2011. Wild-type MIC distributions and epidemiological cutoff values for caspofungin and Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). Antimicrob Agents Chemother 55:2855–2859. [PubMed][CrossRef]

Article metrics loading...



Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in immunocompromised patients. The host immune response plays an essential role in determining the course of exposure to potential fungal pathogens. Depending on the effectiveness of immune response and the burden of organism exposure, fungi can either be cleared or infection can occur and progress to a potentially fatal invasive disease. Nonspecific cellular immunity (i.e., neutrophils, natural killer [NK] cells, and macrophages) combined with T-cell responses are the main immunologic mechanisms of protection. The most common potential mold pathogens include certain hyaline hyphomycetes, endemic fungi, the , and some dematiaceous fungi. Laboratory diagnostics aimed at detecting and differentiating these organisms are crucial to helping clinicians make informed decisions about treatment. The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...



Generic image for table

Click to view


Dual nomenclature of pathogenic pleomorphic fungi

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0002-2015
Generic image for table

Click to view


Common invasive mold infections stratified by risk group and predisposing factors

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0002-2015
Generic image for table

Click to view


Summary of possible antifungal susceptibility profiles for selected opportunistic filamentous fungi

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0002-2015
Generic image for table

Click to view


Epidemiologic cut-off values determined by the CLSI M38-A2 broth microdilution method for and species

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.DMIH2-0002-2015

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error