Aspergillus Polymerase Chain Reaction: Systematic Review of Evidence for Clinical Use in Comparison with Antigen Testing

Clinical Infectious Diseases

Volumn 61, Issue 8, 2015, Pages 1293-1303

  White, P Lewis ^a   Wingard, John R ^b   Bretagne, Stéphane ^c   Löffler, Jürgen ^d   Patterson, Thomas F ^e   Slavin, Monica A ^f   Barnes, Rosemary A ^g   Pappas, Peter G ^h   Donnelly, J Peter ⁱ  

^a PUBLIC HEALTH WALES   (United Kingdom)

^b UNIVERSITY OF FLORIDA HEALTH   (United States)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d UNIVERSITY OF WÜRZBURG   (Germany)

^e SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

^f UNIVERSITY OF MELBOURNE   (Australia)

^g CARDIFF UNIVERSITY   (United Kingdom)

^h UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

ⁱ RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Aspergillosis; Aspergillus; Galactomannan; PCR; D glucan

Indexed keywords

GALACTOMANNAN; BETA GLUCAN; FUNGUS ANTIGEN; MANNAN;

1,3 BETA D GLUCAN ASSAY; ANTIGEN DETECTION; ARTICLE; ASPERGILLUS; ASPERGILLUS POLYMERASE CHAIN REACTION; BLOOD ANALYSIS; BLOOD SAMPLING; CLINICAL EFFECTIVENESS; COMPARATIVE STUDY; ENZYME IMMUNOASSAY; GALACTOMANNAN ENZYME IMMUNOASSAY; HUMAN; INVASIVE ASPERGILLOSIS; LUNG LAVAGE; META ANALYSIS (TOPIC); METHODOLOGY; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; QUALITY CONTROL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SENSITIVITY AND SPECIFICITY; STANDARDIZATION; SYSTEMATIC REVIEW; ASPERGILLOSIS; GENETICS; IMMUNOLOGY; ISOLATION AND PURIFICATION; STANDARDS; STATISTICS AND NUMERICAL DATA;

ANTIGENS, FUNGAL; ASPERGILLOSIS; ASPERGILLUS; BETA-GLUCANS; HUMANS; IMMUNOENZYME TECHNIQUES; MANNANS; POLYMERASE CHAIN REACTION; QUALITY CONTROL; SENSITIVITY AND SPECIFICITY;

EID: 84943255627     PISSN: 10584838     EISSN: 15376591     Source Type: Journal    
DOI: 10.1093/cid/civ507     Document Type: Article

References (93)

1. Ascioglu S, Rex JH, de Pauw B, et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34:7-14.
2. De Pauw B,Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813-21.
3. Hoenigl M, Prattes J, Spiess B, et al. 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 2014; 52:2039-45.
4. White PL, Parr C, Thornton C, Barnes RA. Evaluation of real-time PCR, galactomannan enzyme-linked immunosorbent assay (ELISA), and a novel lateral-flow device for diagnosis of invasive aspergillosis. J Clin Microbiol 2013; 51:1510-6.
5. Zou M, Tang L, Zhao S, et al. Systematic review and meta-analysis of detecting galactomannan in bronchoalveolar lavage fluid for diagnosing invasive aspergillosis. PLoS One 2012; 7:e43347.
6. Guo Y-L, Chen Y-Q,Wang K, et al. Accuracy of BAL galactomannan in diagnosing invasive aspergillosis. Chest 2010; 138:817-24.
7. Leeflang MM, Debets-Ossenkopp YJ, Visser CE, et al. Galactomannan detection for invasive aspergillosis in immunocompromized patients. Cochrane Database Syst Rev 2009; 8:CD007394.
8. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006; 42:1417-27.
9. Lamoth F, Cruciani M, Mengoli C, et al. B-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with haematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukaemia (ECIL-3). Clin Infect Dis 2012; 54:633-43.
10. Karageorgopoulos DE, Vouloumanou EK, Ntziora F, Michalopoulos A, Rafailidis PI, Falagas ME. D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis 2011; 52:750-70.
11. He S, Hang J-P, Zhang L, et al. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-B-D-glucan for invasive fungal infection: focus on cutoff levels. J Microbiol Immun Infect 2014; 48:351-61.
12. Onishi A, Sugiyama D, Kogata Y, et al. Diagnostic accuracy of serum 1,3-?-D-glucan for Pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis. J Clin Microbiol 2012; 50:7-15.
13. Tang CM, Holden DW, Aufauvre-Brown A, Cohen J. The detection of Aspergillus spp. by the polymerase chain reaction and its evaluation in bronchoalveolar lavage fluid. Am Rev Respir Dis 1993; 148:1313-7.
14. White PL, Barnes RA. Aspergillus PCR. In: Latge J-P, Steinbach WJ, eds. Aspergillus fumigatus and aspergillosis. 1st ed. Washington, DC: ASM Press, 2009:373-88.
15. Tuon FF. A systematic literature review on the diagnosis of invasive aspergillosis using the polymerase chain reaction (PCR) from bronchoalveolar lavage clinical samples. Rev Iberoam Micol 2007; 24:89-94.
16. Mengoli C, Cruciani M, Barnes RA, Loeffler J, Donnelly JP. Use of PCR for diagnosis of invasive aspergillosis: systematic review of and metaanalysis. Lancet Infect Dis 2009; 9:89-96.
17. Sun W, Wang K, Gao W, et al. Evaluation of PCR on bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis: a bivariate meta-analysis and systematic review. PLoS One 2011; 6:e28467.
18. Avni T, Levy I, Sprecher H, Yahav D, Leibovici L, Paul M. Diagnostic accuracy of PCR alone compared to galactomannan in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis: a systematic review. J Clin Microbiol 2012; 50:3652-8.
19. Arvanitis M, Ziakas PD, Zacharioudakis IM, Zervou FN, Caliendo AM, Mylonakis E. PCR in diagnosis of invasive aspergillosis: a meta-analysis of diagnostic performance. J Clin Microbiol 2014; 52:3731-42.
20. Swannink CMA, Meis JFGM, Rijs AJMM, Donnelly JP, Verweij PE. Specificity of a sandwich enzyme-linked immunosorbent assay for detecting Aspergillus galactomannan. J Clin Microbiol 1997; 35:257-60.
21. Verweij PE, Erjavec Z, Sluiters W, et al. Detection of antigen in sera of patients with invasive aspergillosis: intra and interlaboratory reproducibility. J Clin Microbiol 1998; 36:1612-6.
22. Bretagne S, Marmorat-Khuoung A, Kuentz M, Latge J-P, Bart-Delabesse E, Cordonnier C. Serum Aspergillus galactomannan antigen testing by sandwich ELISA: practical use in neutropenic patients. J Infect 1997; 35:7-15.
23. Maertens J, Vernhaegen J, Lagrou K, Van Eldere J, Boogaerts M. Screening for circulating galactomannan as non-invasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients a prospective validation. Blood 2001; 97: 1604-10.
24. Maertens J, Verhaegen J, Demuynck H, et al. Autopsy controlled prospective evaluation of serial screening for circulatory galactomannan by a sandwich enzyme linked immunosorbent assay for haematological patients at risk of invasive aspergillosis. J Clin Microbiol 1999; 37:3223-8.
25. Sulahian A, Boutboul F, Ribaud P, Leblanc T, Lacroix C, Derouin F. Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4 year prospective study. Cancer 2001; 91:311-8.
26. Sulahian A, Tabouret M, Ribaud P, et al. Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis. Eur J Clin Microbiol Infect Dis 1996; 15:139-45.
27. Machetti M, Feasi M, Mordini N, et al. Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients. BMT 1998; 21: 917-21.
28. Ulusakarya A, Chachaty E, Vantelon JM, et al. Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme linked immunosrobent assay in neutropenic patients treated for haematological malignancies. Hematol J 2000; 1:111-6.
29. Patterson JE, Zidouh A, Miniter P, Andriole VT, Patterson TF. Hospital epidemiologic surveillance for invasive aspergillosis: patient demographics and the utility of antigen detection. Infect Cont Hosp Epidemiol 1997; 18: 104-8.
30. Williamson ECM, Oliver DA, Johnson EM, Foot ABM, Marks DI, Warnock DW. Aspergillus antigen testing in bone marrow transplant recipients. J Clin Pathol 2000; 53:362-6.
31. Sieman M, Koch-Dorfler M. The Platelia Aspergillus ELISA in diagnosis of invasive pulmonary aspergillosis (IPA). Mycoses 2001; 44:266-72.
32. Fleck E, Rabaud C, Beot S, et al. Invasive aspergillosis in AIDS patients. Med Maladies Infect 1999; 29:401-6.
33. Herrmann J, Gugel A, Freidank H, Bertz H, Finke J. Aspergillus antigen detection: comparison of a new sandwich ELISA with the latex agglutination test in patients with histologically proven invasive aspergillosis. Mycoses 1998; 41(suppl 1):83-5.
34. Kami M, Fukui T, Ogawa S, et al. Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis. Clin Infect Dis 2001; 33:1504-12.
35. Kami M, Ogawa S, Kanda Y, et al. Early diagnosis of central nervous system aspergillosis using polymerase chain reaction, latex agglutination test, and enzyme linked immunosorbent assay. Brit J Haem 1999; 106: 536-7.
36. Salonen J, Lehtonen OP, Terasarvi MR, Nikoskelainen J. Aspergillus antigen in serum urine and bronchoalveolar lavage specimens of neutropenic patients in relation to clinical outcome. Scand J Infect Dis 2000; 32:485-90.
37. Bretagne S, Costa J-M, Bart-Delanesse E, Dhedin N, Rieux C, Cordonnier C. Comparison of serum galactomannan antigen detection and competitive polymerase chain reaction for diagnosing invasive aspergillosis. Clin Infect Dis 1998; 26:1407-12.
38. Stynen D, Goris A, Sarfati J, Latge J-P. A new sensitive sandwich enzyme linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis. J Clin Microbiol 1995; 33:497-500.
39. Fortun J, Martin-Davila P, Alvarez ME, et al. Aspergillus antigenemia sandwich enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. Transplantation 2001; 71:145-9.
40. Sieman M, Koch-Dorfler M, Gaude M. False positive results in premature infants with the Platelia Aspergillus sandwich enzyme linked immunosorbent assay. Mycoses 1998; 41:373-7.
41. Verweij PE, Stynen D, Rijs AJ, et al. Sandwich enzyme linked immunosorbent assay compared to latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients. J Clin Microbiol 1995; 33:1912-4.
42. Verweij PE, Latge J-P, Rijs AJ, et al. Comparison of antigen detection and PCR assay using bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis in patients receiving treatment for haematological malignancies. J Clin Microbiol 1995; 33:3150-3.
43. Rohrlich P, Sarfati J, Mariani P, et al. Prospective sandwich enzymelinked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis. Pediatr Infect Dis 1996; 15:232-7.
44. Tabone M-D, Vu-Thien H, Latge J-P, et al. Value of galactomannan detection by sandwich enzyme linked immunosorbent assay in the early diagnosis and follow-up of invasive aspergillosis. Opportunistic Pathogens 1997; 9:7-13.
45. Verweij PE, Brinkman K, Kremer HP, Kullberg BJ, Meis JF. Aspergillus meningitis: diagnosis by non-culture based microbiological methods and management. J Clin Microbiol 1999; 37:1186-9.
46. Verweij PE, Dompeling EC, Donnelly JP, Schattenberg AV, Meis JF. Serial monitoring of Aspergillus antigen in the early diagnosis of invasive aspergillosis. Preliminary investigations with two examples. Infection 1997; 25:86-9.
47. Machetti M, Zotti M, Veroni L, et al. Antigen detection in the diagnosis and management of a patient with probable cerebral aspergillosis treated with voriconazole. Transpl Infect Dis 2000; 2:140-4.
48. Viscoli C, Machetti M, Gazzola P, et al. Aspergillus galactomannan antigen in the cerebrospinal fluid of bone marrow transplant recipients with probable cerebral aspergillosis. J Clin Microbiol 2002; 40:1496-9.
49. Herbrecht R, Letscher-Bru V, Oprea C, et al. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. J Clin Oncol 2002; 20:1898-906.
50. Marr KA, Balajee SA, McLaughlin L, Tabouret M, Bentsen C,Walsh TJ. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. J Infect Dis 2004; 190:641-9.
51. D'Haese J, Theunissen K, Vermeulen E, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J Clin Microbiol 2012; 50:1258-63.
52. Mennink-Kersten MA, Ruegebrink D, Wasei N, Melchers WJ, Verweij PE. In vitro release by Aspergillus fumigatus of galactofuranose antigens, 1,3-beta-D-glucan, and DNA, surrogate markers used for diagnosis of invasive aspergillosis. J Clin Microbiol 2006; 44:1711-8.
53. Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the 1-3 B-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41:654-9.
54. Pickering JW, Sant HW, Bowles CAP, Roberts WL, Woods GL. Evaluation of 1-3 B-D-glucan assay for the diagnosis of invasive fungal infections. J Clin Microbiol 2005; 43:5957-62.
55. Odabasi Z, Mattiuzzi G, Estey E, et al. B-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cut-off development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 2004; 39:199-205.
56. Tanaka S, Aketagawa J, Takahashi S, et al. Inhibition of high-molecularweight-( 1-3)-beta-D-glucan-dependent activation of a limulus coagulation factor G by laminaran oligosaccharides and curdlan degradation products. Carbohydr Res 1993; 244:115-27.
57. Pazos C, Ponton J, Del Palacio A. Contribution of 1-3 B-D-glucan chromogenic assay to diagnose therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening with circulating galactomannan. J Clin Microbiol 2005; 43: 299-305.
58. Mori T, Ikemoto H, Matsumura M, et al. Evaluation of plasma (1-3)-beta-D-glucan measurement by the kinetic turbidimetric limulus test, for the clinical diagnosis of mycotic infections. Eur J Clin Chem Clin Biochem 1997; 35:553-60.
59. Mitsutake K, Miyazaki T, Tashiro T, et al. Enolase antigen, mannan antigen, Cand-tec antigen, and beta-glucan in patients with candidaemia. J Clin Microbiol 1996; 34:1918-21.
60. Mori T, Matsumura M. Clinical evaluation of diagnostic methods using plasma and/or serum for three mycoses. Jpn J Med Mycol 1999; 40: 223-30.
61. Akamatsu N, Sugawara Y, Kaneko J, Tamura S, Makuuchi M. Preemptive treatment of fungal infection based on the plasma (1-3) B-D-glucan levels after liver transplantation. Infection 2007; 35:346-51.
62. Kami M, Tanaka Y, Kanda Y, et al. Computed tomographic scan of the chest, latex agglutination test and plasma (1-3) B-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients. Haematologica 2000; 85:745-52.
63. Kawazu M, Kanda Y, Nannya Y, et al. Prospective comparison of the diagnostic potential of real-time PCR, double sandwich enzyme linked immunosorbent assay for galactomannan, and a (1-3)-B-D-glucan test in weekly screening for invasive aspergillosis in patients with haematological disorders. J Clin Microbiol 2004; 42:2733-41.
64. Miyazaki T, Kohno S, Mitsuake K, et al. Plasma (1-3) beta-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis and cryptococcosis. J Clin Microbiol 1995; 33:3115-8.
65. Obayashi T, Yoshida M, Mori T, et al. Plasma (1-3) B-D-glucan measurement in diagnosis of invasive deep mycosis and fungal febrile episodes. Lancet 1995; 345:17-20.
66. Metan G, Koc AN, Atalay A, et al. What should be the optimal cut-off of serum B-D-glucan for the detection of invasive pulmonary aspergillosis in patients with haematological malignancies. Scand J Infect Dis 2012; 44:330-6.
67. White PL, Barton R, Guiver M, et al. A consensus on fungal polymerase chain reaction diagnosis? A United Kingdom-Ireland evaluation of polymerase chain reaction methods for detection of systemic fungal infections. J Mol Diagn 2006; 8:376-84.
68. Reichard U, Buchheidt D, Lass-Flörl C, et al. Inter-laboratory comparison of PCR-based identification of Candida and Aspergillus DNA in spiked blood samples. Mycoses 2012; 55:426-34.
69. White PL, Bretagne S, Klingspor L, et al. Aspergillus PCR: one step closer to standardization. J Clin Microbiol 2010; 48:1231-40.
70. White PL, Mengoli C, Bretagne S, et al. Evaluation of Aspergillus PCR protocols for testing serum specimens. J Clin Microbiol 2011; 49: 3842-8.
71. White PL. The European Aspergillus PCR Initiative (EAPCRI)-where do we stand? [abstract W12.2] In: 6th Trends in Medical Mycology conference, Copenhagen, Denmark, 11-14 October 2013.
72. White PL, Perry MD, Moody A, Follett SA, Morgan G, Barnes RA. Evaluation of analytical and preliminary clinical performance of Myconostica MycAssay Aspergillus when testing serum specimens for diagnosis of invasive aspergillosis. J Clin Microbiol 2011; 49:2169-74.
73. White PL, Hibbitts SJ, Perry MD, et al. Evaluation of a commercially developed semi-automated PCR-SERS assay for the diagnosis of invasive fungal disease. J Clin Microbiol 2014; 52:3536-43.
74. Torelli R, Sanguinetti M, Moody A, et al. Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay. J Clin Microbiol 2011; 49: 4273-8.
75. Chong GL, van de SandeWW, Dingemans GJ, et al. Validation of a new Aspergillus real-time PCR assay for direct detection of Aspergillus and azole resistance of Aspergillus fumigatus on bronchoalveolar lavage fluid. J Clin Microbiol 2015; 53:868-74.
76. Lovari R, Metzgar D, Toleno D, et al. Characterisation of a PCR/ESI-MS assay for detection and identification of diverse fungi in bronchoalveolar lavage samples [abstract O219]. In: European Congress of Clinical Microbiology and Infectious Diseases, 2014.
77. Chang SS, Hsieh WH, Liu TS, et al. Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis-a systemic review and meta-analysis. PLoS One 2013; 8:e62323.
78. Lyon GM, Abdul-Ali D, Loeffler J, et al. Development and evaluation of a calibrator material for nucleic acid-based assays for diagnosing aspergillosis. J Clin Microbiol 2013; 51:2403-5.
79. Springer J, Morton CO, Perry M, et al. Multicenter comparison of serum and whole-blood specimens for detection of Aspergillus DNA in high-risk hematological patients. J Clin Microbiol 2013; 51: 1445-50.
80. Rimek D, Garg AP, Haas WH, Kappe R. Identification of contaminating fungal DNA sequences in Zymolyase. J Clin Microbiol 1999; 37:830-1.
81. Loeffler J, Hebart H, Bialek R, et al. Contaminations occurring in fungal PCR assays. J Clin Microbiol 1999; 7:1200-2.
82. White PL, Barnes RA. Aspergillus PCR-platforms, strengths and weaknesses. Med Mycol 2006; 44(suppl):191-8.
83. Jaeger EE, Carroll NM, Choudhury S, et al. Rapid detection and identification of Candida, Aspergillus, and Fusarium species in ocular samples using nested PCR. J Clin Microbiol 2000; 38:2902-8.
84. Perry MD, White PL, Barnes RA. Comparison of four automated nucleic acid extraction platforms for the recovery of DNA from Aspergillus fumigatus. J Med Microbiol 2014; 63:1160-6.
85. Harrison E, Stalhberger T, Whelan R, et al. Aspergillus DNA contamination in blood collection tubes. Diagn Microbiol Infect Dis 2010; 67:392-4.
86. Bretagne S, Costa JM, Marmorat-Khuong A, et al. Detection of Aspergillus species DNA in bronchoalveolar lavage samples by competitive PCR. J Clin Microbiol 1995; 33:1164-8.
87. Millon L, Grenouillet F, Crouzet J, et al. False positive Aspergillus realtime PCR assay due to a nutritional supplement in a bone marrow transplant recipient with GVH disease. Med Mycol 2010; 48:661-4.
88. Lass-Flörl C, Gunsilius E, Gastl G, et al. Diagnosing invasive aspergillosis during antifungal therapy by PCR analysis of blood samples. J Clin Microbiol 2004; 42:4154-7.
89. Morrissey CO, Chen SC, Sorrell TC, et al. 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 2013; 13:519-28.
90. Aguado JM, Vázquez L, Fernández-Ruiz M, Villaescusa T, et al. Serum galactomannan versus a combination of galactomannan and PCR-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial. Clin Infect Dis 2014; 60:405-14.
91. Barnes RA, Stocking K, Bowden S, Poynton MH, White PL. Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway. J Infect 2013; 67:206-14.
92. Cummings JR, Jamison GR, Boudreaux JW, et al. Cross reactivity of non-aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay. Diagn Microbiol Infect Dis 2007; 59:113-5.
93. Van der Linden JW, Snelders E, Arends JP, et al. Rapid diagnosis of azole resistant aspergillosis by direct PCR using tissue specimens. J Clin Microbiol 2010; 48:1478-80.