Skip to main content

Diagnostic Algorithm for Invasive Fungal Infections

  • Chapter
  • First Online:
Clinical Practice of Medical Mycology in Asia

Abstract

Invasive fungal infections (IFI) pose diagnostic and therapeutic challenges due to nonspecific clinical presentations and imaging, particularly in immunocompromised patients. Rapid and accurate diagnosis is crucial for optimal management. Conventional diagnostic methods are considered as “gold standard”; however, they are based on culture, phenotypic identification, and antifungal susceptibility of the isolates, which lack sensitivity and are time-consuming, resulting in delayed diagnosis and therapy. To allow for fast detection and characterization of fungal pathogens, there are sustained efforts to switch to non-culture-based diagnostic methods to provide early and appropriate antifungal treatment. Although detection of biomarkers, such as 1, 3-β-d-glucan, (BDG), galactomannan (GM), Candida mannan (Mn), and Candida-anti-mannan antibodies (A-Mn) are useful for rapid diagnosis, there are still issues associated with sensitivities, specificities, and standardization in specific cohort of patients. Histopathological examination of tissue biopsy can provide rapid diagnosis; however, invasive specimens are often not readily available due to associated comorbidities. PCR-based assays, DNA sequencing, and other molecular methods have shown great promise to be used as primary diagnostic tools alone or to complement culture-based methods; however, these tests require standardization and are yet to be incorporated as a diagnostic criterion in routine clinical laboratory. In the absence of detection of BDG and GM biomarkers, DNA-based detection methods are essential for the diagnosis of mucormycosis. T2 magnetic resonance (T2MR), a nano-platform, approved by the US FDA is a timely and important advancement in the early diagnosis of candidemia. The test has a sensitivity of 89% in patients at the time of blood culture positivity. Likewise, proteomic approaches such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has also been applied directly to blood specimens to identify Candida species with reduced turnaround time. Two lateral flow assays for point-of-care diagnosis of cryptococcosis and aspergillosis have also been developed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Slavin MA, Chakrabarti A. Opportunistic fungal infections in the Asia-Pacific region. Med Mycol. 2012;50:18–25.

    Article  PubMed  Google Scholar 

  2. Khan ZU, Ahmad S. Non-culture-based diagnostic methods for the diagnosis of invasive candidiasis: are they helpful to clinicians? J Kuwait Med Assoc. 2013;45:4–14.

    Google Scholar 

  3. Ramanan P, Wengenack NL, Theel ES. Laboratory diagnostics for fungal infections: a review of current and future diagnostic assays. Clin Chest Med. 2017;38:535–54.

    Article  PubMed  Google Scholar 

  4. Halliday CL, Kidd SE, Sorrell TC, Chen SC. Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer? Pathology. 2015;47:257–69.

    Article  CAS  PubMed  Google Scholar 

  5. Batzlaff CM, Limper AH. When to consider the possibility of a fungal infection: an overview of clinical diagnosis and laboratory approaches. Clin Chest Med. 2017;38:385–91.

    Article  PubMed  Google Scholar 

  6. Ostrosky-Zeichner L, Sable C, Sobel J, Alexander BD, Donowitz G, Kan V, Kauffman CA, Kett D, Larsen RA, Morrison V, Nucci M, Pappas PG, Bradley ME, Major S, Zimmer L, Wallace D, Dismukes WE, Rex JH. Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting. Eur J Clin Microbiol Infect Dis. 2007;26:271–6.

    Article  CAS  PubMed  Google Scholar 

  7. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, Meersseman W, Akova M, Arendrup MC, Arikan-Akdagli S, Bille J, Castagnola E, Cuenca-Estrella M, Donnelly JP, Groll AH, Herbrecht R, Hope WW, Jensen HE, Lass-Flörl C, Petrikkos G, Richardson MD, Roilides E, Verweij PE, Viscoli C, Ullmann AJ, ESCMID Fungal Infection Study Group. ESCMID∗ guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012;18(Suppl 7):19–37.

    Article  CAS  PubMed  Google Scholar 

  8. Neofytos D, Railkar R, Mullane KM, Fredricks DN, Granwehr B, Marr KA, Almyroudis NG, Kontoyiannis DP, Maertens J, Fox R, Douglas C, Iannone R, Kauh E, Shire N. Correlation between circulating fungal biomarkers and clinical outcome in invasive aspergillosis. PLoS One. 2015;10(6):e0129022.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. 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, for the Australasian Leukaemia Lymphoma Group and the Australia and New Zealand Mycology Interest Group. 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.

    Article  CAS  PubMed  Google Scholar 

  10. Ruhnke M, Behre G, Buchheidt D, Christopeit M, Hamprecht A, Heinz W, et al. Diagnosis of invasive fungal diseases in haematology and oncology. 2018 update of the recommendations of the infectious diseases working party of the German Society for Hematology and Medical Oncology (AGIHO). Mycoses. 2018;61(11):796–813. https://doi.org/10.1111/myc.12838.

    Article  PubMed  Google Scholar 

  11. McCarty TP, Pappas PG. Invasive candidiasis. Infect Dis Clin North Am. 2016;30:103–24.

    Article  PubMed  Google Scholar 

  12. Eggimann P, Bille J, Marchetti O. Diagnosis of invasive candidiasis in the ICU. Ann Intensive Care. 2011;1:1–37.

    Article  Google Scholar 

  13. Ahmed A, Baronia AK, Azim A, Marak RSK, Yadav R, Sharma P, Gurjar M, Poddar B, Singh RK. External validation of risk prediction scores for invasive candidiasis in a medical/surgical intensive care unit: an observational study. Indian J Crit Care Med. 2017;21:514–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. León C, Ruiz-Santana S, Saavedra P, Galván B, Blanco A, Castro C, Balasini C, Utande-Vázquez A, González de Molina FJ, Blasco-Navalproto MA, López MJ, Charles PE, Martín E, Hernández-Viera MA, Cava Study Group. Usefulness of the “Candida score” for discriminating between Candida colonization and invasive candidiasis in non-neutropenic critically ill patients: a prospective multicenter study. Crit Care Med. 2009;37:1624–33.

    Article  PubMed  Google Scholar 

  15. Ostrosky-Zeichner L, Pappas PG, Shoham S, Reboli A, Barron MA, Sims C, Wood C, Sobel JD. Improvement of a clinical prediction rule for clinical trials on prophylaxis for invasive candidiasis in the intensive care unit. Mycoses. 2011;54:46–51.

    Article  PubMed  Google Scholar 

  16. Hermsen ED, Zapapas MK, Maiefski M, Rupp ME, Freifeld AG, Kalil AC. Validation and comparison of clinical prediction rules for invasive candidiasis in intensive care unit patients: a matched case-control study. Crit Care. 2011;15:R198.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chapman RL. Candida infections in the neonate. Curr Opin Pediatr. 2003;15:97–102.

    Article  PubMed  Google Scholar 

  18. Al-Sweih N, Khan Z, Khan S, Devarajan LV. Neonatal candidaemia in Kuwait: a 12-year study of risk factors, species spectrum and antifungal susceptibility. Mycoses. 2009;52:518–23.

    Article  PubMed  Google Scholar 

  19. Hammoud MS, Al-Taiar A, Fouad M, Raina A, Khan Z. Persistent candidemia in neonatal care units: risk factors and clinical significance. Int J Infect Dis. 2013;17:e624–8.

    Article  PubMed  Google Scholar 

  20. Herbrecht R, Bories P, Moulin JC, Ledoux MP, Letscher-Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Ann N Y Acad Sci. 2012;1272:23–30.

    Article  PubMed  Google Scholar 

  21. Pagano L, Akova M, Dimopoulos G, Herbrecht R, Drgona L, Blijlevens N. Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. J Antimicrob Chemother. 2011;66(Suppl 1):i5–14.

    Article  CAS  PubMed  Google Scholar 

  22. Samarakoon P, Soubani A. Invasive pulmonary aspergillosis in patients with COPD: a report of five cases and systematic review of the literature. Chron Respir Dis. 2008;5:19–27.

    Article  CAS  PubMed  Google Scholar 

  23. Stevens DA, Melikian GL. Aspergillosis in the ‘nonimmunocompromised’ host. Immunol Invest. 2011;40:751–66.

    Article  CAS  PubMed  Google Scholar 

  24. Mezger M, Einsele H, Loeffler J. Genetic susceptibility to infections with Aspergillus fumigatus. Crit Rev Microbiol. 2010;36:168–77.

    Article  CAS  PubMed  Google Scholar 

  25. Meis JF, Chakrabarti A. Changing epidemiology of an emerging infection: zygomycosis. Clin Microbiol Infect. 2009;15(Suppl 5):10–4.

    Article  PubMed  Google Scholar 

  26. Millon L, Herbrecht R, Grenouillet F, Morio F, Alanio A, Letscher-Bru V, Cassaing S, Chouaki T, Kauffmann-Lacroix C, Poirier P, Toubas D, Augereau O, Rocchi S, Garcia-Hermoso D, Bretagne S, French Mycosis Study Group. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF). Clin Microbiol Infect. 2016;22:810.e1–8.

    Article  CAS  Google Scholar 

  27. Georgiadou SP, Sipsas NV, Marom EM, Kontoyiannis DP. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis. 2011;52:1144–55.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chamilos G, Marom EM, Lewis RE, Lionakis MS, Kontoyiannis DP. Predictors of pulmonary zygomycosis versus invasive pulmonary aspergillosis in patients with cancer. Clin Infect Dis. 2005;41:60–6.

    Article  PubMed  Google Scholar 

  29. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al.; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. 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;46:1813–1821.

    Google Scholar 

  30. Katragkou A, Fisher BT, Groll AH, Roilides E, Walsh TJ. Diagnostic imaging and invasive fungal diseases in children. J Pediatric Infect Dis Soc. 2017;6(suppl. 1):S22–31.

    Article  PubMed  Google Scholar 

  31. Schelenz S, Barnes RA, Barton RC, Cleverley JR, Lucas SB, Kibbler CC, Denning DW. British Society for Medical Mycology Best Practice recommendations for the diagnosis of serious fungal diseases. Lancet Infect Dis. 2015;15:461–74.

    Article  PubMed  Google Scholar 

  32. Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev 2011;24:247–280.mxf

    Article  PubMed  PubMed Central  Google Scholar 

  33. Beirão F, Araujo R. State of the art diagnostic of mold diseases: a practical guide for clinicians. Eur J Clin Microbiol Infect Dis. 2013;32:3–9.

    Article  PubMed  CAS  Google Scholar 

  34. Clancy CJ, Nguyen MH. Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis. 2013;56:1284–92.

    Article  PubMed  Google Scholar 

  35. Sinha K, Tendolkar U, Mathur M. Comparison of conventional broth blood culture technique and manual lysis centrifugation technique for detection of fungemia. Indian J Med Microbiol. 2009;27:79–80.

    CAS  PubMed  Google Scholar 

  36. Clancy CJ, Pappas PG, Vazquez J, Judson MA, Kontoyiannis DP, Thompson GR 3rd, Garey KW, Reboli A, Greenberg RN, Apewokin S, Lyon GM 3rd, Ostrosky-Zeichner L, Wu AHB, Tobin E, Nguyen MH, Caliendo AM. Detecting infections rapidly and easily for candidemia trial, part 2 (DIRECT2): a prospective, multicenter study of the T2Candida panel. Clin Infect Dis. 2018;66:1678–86.

    Article  CAS  PubMed  Google Scholar 

  37. Clancy CJ, Nguyen MH. T2 magnetic resonance for the diagnosis of bloodstream infections: charting a path forward. J Antimicrob Chemother. 2018;73(suppl_4):iv2–5.

    Article  CAS  PubMed  Google Scholar 

  38. Randhawa HS, Chowdhary A, Preeti Sinha K, Kowshik T, Vijayan VK. Evaluation of peptone glucose fluconazole agar as a selective medium for rapid and enhanced isolation of Aspergillus fumigatus from the respiratory tract of bronchopulmonary aspergillosis patients colonized by Candida albicans. Med Mycol. 2006;44:343–8.

    Article  CAS  PubMed  Google Scholar 

  39. Chakrabarti A, Das A, Sharma A, Panda N, Das S, Gupta KL, Sakhuja V. Ten years’ experience in zygomycosis at a tertiary care centre in India. J Infect. 2001;42:261–6.

    Article  CAS  PubMed  Google Scholar 

  40. Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin Microbiol Infect. 2009;15(Suppl 5):60–5.

    Article  PubMed  Google Scholar 

  41. Skiada A, Lanternier F, Groll AH, Pagano L, Zimmerli S, Herbrecht R, Lortholary O, Petrikkos GL, European Conference on Infections in Leukemia. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica. 2013;98:492–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Preuner S, Lion T. Species-specific identification of a wide range of clinically relevant fungal pathogens by the Luminex® xMAP technology. Methods Mol Biol. 2013;968:119–39.

    Article  CAS  PubMed  Google Scholar 

  43. Jamal WY, Ahmad S, Khan ZU, Rotimi VO. Comparative evaluation of two matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of clinically significant yeasts. Int J Infect Dis. 2014;26:167–70.

    Article  CAS  PubMed  Google Scholar 

  44. Lee HS, Shin JH, Choi MJ, Won EJ, Kee SJ, Kim SH, Shin MG, Suh SP. Comparison of the Bruker biotyper and VITEK MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry systems using a formic acid extraction method to identify common and uncommon yeast isolates. Ann Lab Med. 2017;37:223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Bao JR, Master RN, Azad KN, Schwab DA, Clark RB, Jones RS, Moore EC, Shier KL. Rapid, accurate identification of Candida auris by using a novel matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) database (library). J Clin Microbiol. 2018;56. pii: e01700-17.

    Google Scholar 

  46. Shao J, Wan Z, Li R, Yu J. Species identification and delineation of pathogenic mucorales by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol. 2018;56. pii: e01886-17.

    Google Scholar 

  47. Stein M, Tran V, Nichol KA, Lagacé-Wiens P, Pieroni P, Adam HJ, Turenne C, Walkty AJ, Normand AC, Hendrickx M, Piarroux R, Karlowsky JA. Evaluation of three MALDI-TOF mass spectrometry libraries for the identification of filamentous fungi in three clinical microbiology laboratories in Manitoba, Canada. Mycoses. 2018;61:743–53.

    Article  CAS  PubMed  Google Scholar 

  48. Vella A, De Carolis E, Mello E, Perlin DS, Sanglard D, Sanguinetti M, Posteraro B. Potential use of MALDI-TOF mass spectrometry for rapid detection of antifungal resistance in the human pathogen Candida glabrata. Sci Rep. 2017;7:9099.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Miceli MH, Maertens J. Role of non-culture-based tests, with an emphasis on galactomannan testing for the diagnosis of invasive aspergillosis. Semin Respir Crit Care Med. 2015;36:650–61.

    Article  PubMed  Google Scholar 

  50. Mokaddas E, Burhamah MH, Khan ZU, Ahmad S. Levels of (1→3)-β-D-glucan, Candida mannan and Candida DNA in serum samples of pediatric cancer patients colonized with Candida species. BMC Infect Dis. 2010;10:292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Lamoth F, Cruciani M, Mengoli C, Castagnola E, Lortholary O, Richardson M, Marchetti O, Third European Conference on Infections in Leukemia (ECIL-3). 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. 2012;54:633–43.

    Article  PubMed  Google Scholar 

  52. Marchetti O, Lamoth F, Mikulska M, Viscoli C, Verweij P, Bretagne S, European Conference on Infections in Leukemia (ECIL) Laboratory Working Groups. ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant. 2012;47:846–54.

    Article  CAS  PubMed  Google Scholar 

  53. Maartens G, Stewart A, Griesel R, Kengne AP, Dube F, Nicol M, Rangaka MX, Mendelson M. Development of a clinical prediction rule to diagnose Pneumocystis jirovecii pneumonia in the World Health Organization’s algorithm for seriously ill HIV-infected patients. South Afr J HIV Med. 2018;19:851.

    Article  PubMed  PubMed Central  Google Scholar 

  54. White PL, Posso RB, Gorton RL, Price JS, Wey E, Barnes RA. An evaluation of the performance of the Dynamiker® fungus (1-3)-β-D-glucan assay to assist in the diagnosis of pneumocystis pneumonia. Med Mycol. 2018;56:778–81.

    Article  CAS  PubMed  Google Scholar 

  55. Alam FF, Mustafa AS, Khan ZU. Comparative evaluation of (1, 3)-β-D-glucan, mannan and anti-mannan antibodies, and Candida species-specific snPCR in patients with candidemia. BMC Infect Dis. 2007;7:103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Mikulska M, Calandra T, Sanguinetti M, Poulain D, Viscoli C, Third European Conference on Infections in Leukemia Group. The use of mannan antigen and anti-mannan antibodies in the diagnosis of invasive candidiasis: recommendations from the Third European Conference on Infections in Leukemia. Crit Care. 2010;14:R222.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Mokaddas E, Khan ZU, Ahmad S, Nampoory MR, Burhamah M. Value of (1-3)-β-d-glucan, Candida mannan and Candida DNA detection in the diagnosis of candidaemia. Clin Microbiol Infect. 2011;17:1549–53.

    Article  CAS  PubMed  Google Scholar 

  58. Clancy CJ, Nguyen MH. Diagnosing invasive candidiasis. J Clin Microbiol. 2018;56: pii: e01909-17.

    Google Scholar 

  59. Clancy CJ, Nguyen MH. Non-culture diagnostics for invasive candidiasis: promise and unintended consequences. J Fungi (Basel). 2018;4. pii: E27.

    Google Scholar 

  60. Maertens J, Theunissen K, Verbeken E, Lagrou K, Verhaegen J, Boogaerts M, Eldere JV. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Br J Haematol. 2004;126:852–60.

    Article  CAS  PubMed  Google Scholar 

  61. Cuenca-Estrella M, Bassetti M, Lass-Flörl C, Rácil Z, Richardson M, Rogers TR. Detection and investigation of invasive mould disease. J Antimicrob Chemother. 2011;66(Suppl 1):15–24.

    Article  CAS  Google Scholar 

  62. Khan ZU, Ahmad S, Mokaddas E, Said T, Nair MP, Halim MA, Nampoory MR, McGinnis MR. Cerebral aspergillosis diagnosed by detection of Aspergillus flavus-specific DNA, galactomannan and (1-3)-β-D-glucan in clinical specimens. J Med Microbiol. 2007;56:129–32.

    Article  CAS  PubMed  Google Scholar 

  63. Mokaddas E, Burhamah MH, Ahmad S, Khan ZU. Invasive pulmonary aspergillosis due to Aspergillus terreus: value of DNA, galactomannan and (1-3)-β-D-glucan detection in serum samples as an adjunct to diagnosis. J Med Microbiol. 2010;59:1519–23.

    Article  CAS  PubMed  Google Scholar 

  64. Zou M, Tang L, Zhao S, Zhao Z, Chen L, Chen P, Huang Z, Li J, Chen L, Fan X. Systematic review and meta-analysis of detecting galactomannan in bronchoalveolar lavage fluid for diagnosing invasive aspergillosis. PLoS One. 2012;7:e43347.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ahmad S, Khan Z. Invasive candidiasis: a review of non-culture-based laboratory diagnostic methods. Indian J Med Microbiol. 2012;30:264–9.

    Article  CAS  PubMed  Google Scholar 

  67. Ahmad S, Khan Z, Mustafa AS, Khan ZU. Semi-nested PCR for diagnosis of candidemia: comparison with culture, antigen detection, and biochemical methods for species identification. J Clin Microbiol. 2002;40:2483–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ahmad S, Mustafa AS, Khan Z, Al-Rifaiy AI, Khan ZU. PCR-enzyme immunoassay of rDNA in the diagnosis of candidemia and comparison with amplicon detection by agarose gel electrophoresis. Int J Med Microbiol. 2004;294:45–51.

    Article  CAS  PubMed  Google Scholar 

  69. Asadzadeh M, Ahmad S, Hagen F, Meis JF, Al-Sweih N, Khan Z. Simple, low-cost detection of Candida parapsilosis complex isolates and molecular fingerprinting of Candida orthopsilosis strains in Kuwait by ITS region sequencing and amplified fragment length polymorphism analysis. PLoS One. 2015;10:e0142880.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Al-Obaid K, Asadzadeh M, Ahmad S, Khan Z. Population structure and molecular genetic characterization of clinical Candida tropicalis isolates from a tertiary-care hospital in Kuwait reveal infections with unique strains. PLoS One. 2017;12:e0182292.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Khan Z, Ahmad S, Al-Sweih N, Joseph L, Alfouzan W, Asadzadeh M. Increasing prevalence, molecular characterization and antifungal drug susceptibility of serial Candida auris isolates in Kuwait. PLoS One. 2018;13:e0195743.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Ahmad S, Al-Mahmeed M, Khan ZU. Characterization of Trichosporon species isolated from clinical specimens in Kuwait. J Med Microbiol. 2005;54:639–46.

    Article  CAS  PubMed  Google Scholar 

  73. Khan ZU, Al-Sweih NA, Ahmad S, Al-Kazemi N, Khan S, Joseph L, Chandy R. Outbreak of fungemia among neonates caused by Candida haemulonii resistant to amphotericin B, itraconazole and fluconazole. J Clin Microbiol. 2007;45:2025–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Al-Sweih N, Ahmad S, Khan S, Joseph L, Asadzadeh M, Khan Z. Cyberlindnera fabianii fungemia outbreak in preterm neonates in Kuwait and literature review. Mycoses. 2019;62(1):51–61. https://doi.org/10.1111/myc.12846.

    Article  PubMed  Google Scholar 

  75. Nguyen MH, Wissel MC, Shields RK, Salomoni MA, Hao B, Press EG, Shields RM, Cheng S, Mitsani D, Vadnerkar A, Silveira FP, Kleiboeker SB, Clancy CJ. Performance of Candida real-time polymerase chain reaction, β-D-glucan assay, and blood cultures in the diagnosis of invasive candidiasis. Clin Infect Dis. 2012;54:1240–8.

    Article  CAS  PubMed  Google Scholar 

  76. White PL, Mengoli C, Bretagne S, Cuenca-Estrella M, Finnstrom N, Klingspor L, Melchers WJ, McCulloch E, Barnes RA, Donnelly JP, Loeffler J, European Aspergillus PCR Initiative (EAPCRI). Evaluation of Aspergillus PCR protocols for testing serum specimens. J Clin Microbiol. 2011;49:3842–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Sun W, Wang K, Gao W, Su X, Qian Q, Lu X, Song Y, Guo Y, Shi Y. Evaluation of PCR on bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis: a bivariate meta-analysis and systematic review. PLoS One. 2011;6:e28467.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Lucignano B, Ranno S, Liesenfeld O, Pizzorno B, Putignani L, Bernaschi P. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol. 2011;49:2252–8.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Fernández-Cruz A, Marín M, Kestler M, Alcalá L, Rodriguez-Créixems M, Bouza E. The value of combining blood culture and SeptiFast data for predicting complicated bloodstream infections caused by gram-positive bacteria or Candida species. J Clin Microbiol. 2013;51:1130–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Elges S, Arnold R, Liesenfeld O, Kofla G, Mikolajewska A, Schwartz S. Prospective evaluation of the SeptiFAST multiplex real-time PCR assay for surveillance and diagnosis of infections in haematological patients after allogeneic stem cell transplantation compared to routine microbiological assays and an in-house real-time PCR method. Mycoses. 2017;60:781–8.

    Article  CAS  PubMed  Google Scholar 

  82. Pfaller MA, Wolk DM, Lowery TJ. T2MR and T2Candida: novel technology for the rapid diagnosis of candidemia and invasive candidiasis. Future Microbiol. 2016;11:103–17.

    Article  CAS  PubMed  Google Scholar 

  83. Zervou FN, Zacharioudakis IM, Kurpewski J, Mylonakis E. T2 magnetic resonance for fungal diagnosis. Methods Mol Biol. 2017;1508:305–19.

    Article  CAS  PubMed  Google Scholar 

  84. Muñoz P, Vena A, Machado M, Martínez-Jiménez MC, Gioia F, Gómez E. T2MR contributes to the very early diagnosis of complicated candidaemia. A prospective study. J Antimicrob Chemother. 2018;73(suppl 4):iv13–9.

    Article  PubMed  CAS  Google Scholar 

  85. Muñoz P, Vena A, Machado M, Gioia F, Martínez-Jiménez MC, Gómez E. T2Candida MR as a predictor of outcome in patients with suspected invasive candidiasis starting empirical antifungal treatment: a prospective pilot study. J Antimicrob Chemother. 2018;73(suppl 4):iv6–iv12.

    Article  PubMed  CAS  Google Scholar 

  86. Patch ME, Weisz E, Cubillos A, Estrada SJ, Pfaller MA. Impact of rapid, culture-independent diagnosis of candidaemia and invasive candidiasis in a community health system. J Antimicrob Chemother. 2018;73(suppl 4):iv27–30.

    Article  CAS  PubMed  Google Scholar 

  87. Prattes J, Heldt S, Eigl S, Hoenigl M. Point of care testing for the diagnosis of fungal infections: are we there yet? Curr Fungal Infect Rep. 2016;10:43–50.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Heldt S, Hoenigl M. Lateral flow assays for the diagnosis of invasive Aspergillosis: current status. Curr Fungal Infect Rep. 2017;11:45–51.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Tang MW, Clemons KV, Katzenstein DA, Stevens DA. The cryptococcal antigen lateral flow assay: a point-of-care diagnostic at an opportune time. Crit Rev Microbiol. 2016;42:634–42.

    CAS  PubMed  Google Scholar 

  90. Sims CR, Jaijakul S, Mohr J, Rodriguez J, Finkelman M, Ostrosky-Zeichner L. Correlation of clinical outcomes with β-glucan levels in patients with invasive candidiasis. J Clin Microbiol. 2012;50:2104–6.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, Maertens J, Lortholary O, Donnelly PJ, Schlamm HT, Troke PF, Netea MG, Herbrecht R. Early serum galactomannan trend as a predictor of outcome of invasive aspergillosis. J Clin Microbiol. 2012;50:2330–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Shi LN, Li FQ, Lu JF, Kong XX, Wang SQ, Huang M, Shao HF, Shao SH. Antibody specific to thioredoxin reductase as a new biomarker for serodiagnosis of invasive aspergillosis in non-neutropenic patients. Clin Chim Acta. 2012;413:938–43.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ziauddin Khan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Khan, Z., Ahmad, S. (2020). Diagnostic Algorithm for Invasive Fungal Infections. In: Chakrabarti, A. (eds) Clinical Practice of Medical Mycology in Asia. Springer, Singapore. https://doi.org/10.1007/978-981-13-9459-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-9459-1_12

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-9458-4

  • Online ISBN: 978-981-13-9459-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics