Laboratory diagnosis of mucormycosis: current status and future perspectives

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 Kwon-Chung K. Taxonomy of fungi causing mucormycosis and entomophthoramycosis (zygomycosis) and nomenclature of the disease: molecular mycologic perspectives. Clin. Infect. Dis. 54, S8–S15 (2012).• Reviews the progress and changes in taxonomy and nomenclature of Zygomycota and the disease zygomycosis.
  MedlineGoogle Scholar
• 2 Hibbett DS, Binder M, Bischoff JF et al. A higher-level phylogenetic classification of the fungi. Mycol. Res. 111(Pt 5), 509–547 (2007).
  MedlineGoogle Scholar
• 3 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. 41, 60–66 (2005).
  MedlineGoogle Scholar
• 4 Gil-Lamaignere C, Simitsopoulou M, Roilides E, Maloukou A, Winn RM, Walsh TJ. Interferon-γ and granulocyte-macrophage colony-stimulating factor augment the activity of polymorphonuclear leukocytes against medically important zygomycetes. J. Infect. Dis. 191, 1180–1187 (2005).
  Medline CASGoogle Scholar
• 5 Lanternier F, Sun H-Y, Ribaud P, Singh N, Kontoyiannis DP, Lortholary O. Mucormycosis in organ and stem cell transplant recipients. Clin. Infect. Dis. 54, 1–8 (2012).
  MedlineGoogle Scholar
• 6 Buzina W, Braun H, Freudenschuss K, Lackner A, Habermann W, Stammberger H. Fungal biodiversity – as found in nasal mucus. Med. Mycol. 41, 149–161 (2003).
  Medline CASGoogle Scholar
• 7 Kontoyiannis DP, Lewis RE. How I treat mucormycosis. Blood 118, 1216–1224 (2011).• Comprehensive update on how to best deal with mucormycosis. Critical reflects pro and cons of various treatment strategies.
  Medline CASGoogle Scholar
• 8 Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin. Microbiol. Rev. 13, 236–301 (2000).
  Medline CASGoogle Scholar
• 9 Richardson M. The ecology of the zygomycetes and its impact on environmental exposure. Clin. Microbiol. Infect. 15, 2–9 (2009).
  MedlineGoogle Scholar
• 10 Paltauf A. Mucormycosis mucorina. Virchows Arch. Pathol. Anat. 102, 543–564 (1885).
  Google Scholar
• 11 Skiada A, Pagano L, Groll A et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin. Microbiol. Infect. 17, 1859–1867 (2011).
  Medline CASGoogle Scholar
• 12 Kume H, Yamazaki T, Abe M, Tanuma H, Okudaira M, Okayasu I. Increase in aspergillosis and severe mycotic infection in patients with leukemia and MDS: comparison of the data from the Annual of the Pathological Autopsy Cases in Japan in 1993 and 1997. Pathol. Int. 53, 744–750 (2003) (1989).
  MedlineGoogle Scholar
• 13 Funada H, Matsuda T. Pulmonary mucormycosis in a hematology ward. Intern. Med. 35, 540–544 (1996).
  Medline CASGoogle Scholar
• 14 Chakrabarti A, Das A, Mandal J et al. The rising trend of invasive zygomycosis in patients with uncontrolled diabetes mellitus. Med. Mycol. 44, 335–342 (2006).
  MedlineGoogle Scholar
• 15 Spellberg B, Edwards J, Ibrahim A. Novel perspectives on mucormycosis: pathophysiology, presentation and management. Clin. Microbiol. Rev. 18, 556–569 (2005).
  Medline CASGoogle Scholar
• 16 Chakrabarti A, Shivaprakash MR, Curfs-Breuker I, Baghela A, Klaassen CH, Meis JF. Apophysomyces elegans: epidemiology, amplified fragment length polymorphism typing, and in vitro antifungal susceptibility pattern. J. Clin. Microbiol. 48, 4580–4585 (2010).
  Medline CASGoogle Scholar
• 17 Marak RS, Misra R, Ansari MS et al. Successful medical management of renal zygomycosis: a summary of two cases and a review of the Indian literature. Med. Mycol. 48, 1088–1095 (2010).
  MedlineGoogle Scholar
• 18 Chakrabarti A, Singh R. The emerging epidemiology of mould infections in developing countries. Curr. Opin. Infect. Dis. 24, 521–526 (2011).
  MedlineGoogle Scholar
• 19 Ingram CW, Sennesh J, Cooper JN, Perfect JR. Disseminated zygomycosis – report of 4 cases and review. Rev. Infect. Dis. 11, 741–754 (1989).
  Medline CASGoogle Scholar
• 20 Johnson CB, Ahmeti M, Tyroch AH, Zuckerman MJ, Hakim MN. Gastric mucormycosis as a cause of life-threatening upper gastrointestinal bleeding in a trauma patient. Am. Surg. 76(7), E76–77 (2010).
  MedlineGoogle Scholar
• 21 Weng DE, Wilson WH, Little R, Walsh TJ. Successful medical management of isolated renal zygomycosis: case report and review. Clin. Infect. Dis. 26, 601–605 (1998).
  Medline CASGoogle Scholar
• 22 Walsh TJ, Hiemenz JW, Seibel NL et al. Amphotericin B lipid complex for invasive fungal infections: analysis of safety and efficacy in 556 cases. Clin. Infect. Dis. 26, 1383–1396 (1998).
  Medline CASGoogle Scholar
• 23 Spellberg B, Ibrahim A, Roilides E et al. Combination Therapy for mucormycosis: why, what and how? Clin. Infect. Dis. 54, S73–S78 (2012).
  Medline CASGoogle Scholar
• 24 Ibrahim AS, Gebremariam T, Fu Y, Edwards JE, Spellberg B. Combination echinocandin-polyene treatment of murine mucormycosis. Antimicrob. Agents Chemother. 52, 1556–1558 (2008).
  Medline CASGoogle Scholar
• 25 Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary and disseminated mucormycosis (zygomycosis). Clin. Infect. Dis. 54, S55–S60 (2012).
  MedlineGoogle Scholar
• 26 Lionakis MS, Kontoyiannis DP. The significance of isolation of saprophytic molds from the lower respiratory tract in patients with cancer. Cancer 100, 165–172 (2004).
  MedlineGoogle Scholar
• 27 Monheit JE, Cowan DF, Moore DG. Rapid detection of fungi in tissues using calcofluor white and fluorescence microscopy. Arch. Pathol. Lab. Med. 108, 616–618 (1984).
  Medline CASGoogle Scholar
• 28 Lass-Flörl C. Zygomycosis: conventional laboratory diagnosis. Clin. Microbiol. Infect. 5, 60–65 (2009).
  Google Scholar
• 29 Lass-Flörl C, Resch G, Nachbaur D et al. The value of computed tomography-guided percutaneous lung biopsy for diagnosis of invasive fungal infection in immunocompromised patients. Clin. Infect. Dis. 45, e101–104 (2007).
  MedlineGoogle Scholar
• 30 Frater JL, Hall GS, Procop GW. Histologic features of zygomycosis: emphasis on perineural invasion and fungal morphology. Arch. Pathol. Lab. Med. 125, 375–378 (2001).
  Medline CASGoogle Scholar
• 31 Kontoyiannis DP, Chamilos G, Hassan SA, Lewis RE, Albert ND, Tarrand JJ. Increased culture recovery of Zygomycetes under physiologic temperature conditions. Am. J. Clin. Pathol. 127, 208–212 (2007).
  MedlineGoogle Scholar
• 32 Padhye AA, Ajello L. Simple method of inducing sporulation by Apophysomyces elegans and Saksenaea vasiformis. J. Clin. Microbiol. 26, 1861–1863 (1988).
  Medline CASGoogle Scholar
• 33 Lass-Flörl C. Diagnosing invasive fungal diseases – limitations of microbiological diagnostic methods. Expert. Opin. Med. Diagn. 3, 461–470 (2009).
  MedlineGoogle Scholar
• 34 Vitale RG, de Hoog GS, Schwarz P et al. Antifungal susceptibility and phylogeny of opportunistic members of the order mucorales. J. Clin. Microbiol. 50, 66–75 (2012).• Highlights the importance of accurate fungal species identification for antifungal treatment choices and give a comprehensive overview of medically important Mucorales.
  Medline CASGoogle Scholar
• 35 Dako. www.dako.com
  Google Scholar
• 36 Neblett Fanfair R, Benedict K, Bos J et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N. Engl. J. Med. 367, 2214–2225 (2012).
  MedlineGoogle Scholar
• 37 Hayden RT, Qian X, Procop GW, Roberts GD, Lloyd RV. In situ hybridization for the identification of filamentous fungi in tissue section. Diagn. Mol. Pathol. 11, 119–126 (2002).
  Medline CASGoogle Scholar
• 38 Bergan T, Hollum AB, Vangdal M. Evaluation of four commercial biochemical test systems for identification of yeasts. Eur. J. Clin. Microbiol. 1, 217–222 (1982).
  Medline CASGoogle Scholar
• 39 Freydiere AM, Guinet R, Boiron P. Yeast identification in the clinical microbiology laboratory: phenotypical methods. Med. Mycol. 39, 9–33 (2001).
  Medline CASGoogle Scholar
• 40 Meletiadis J, Arabatzis M, Bompola M et al. Comparative evaluation of three commercial identification systems using common and rare bloodstream yeast isolates. J. Clin. Microbiol. 49, 2722–2727 (2011).
  MedlineGoogle Scholar
• 41 Ramani R, Gromadzki S, Pincus DH, Salkin IF, Chaturvedi V. Efficacy of API 20C and ID 32C systems for identification of common and rare clinical yeast isolates. J. Clin. Microbiol. 36, 3396–3398 (1998).
  Medline CASGoogle Scholar
• 42 Schwarz P, Lortholary O, Dromer F, Dannaoui E. Carbon assimilation profiles as a tool for identification of zygomycetes. J. Clin. Microbiol. 45, 1433–1439 (2007).
  Medline CASGoogle Scholar
• 43 Garcia-Hermoso D, Hoinard D, Gantier J-C, Grenouillet F, Dromer F, Dannaoui E. Molecular and phenotypic evaluation of Lichtheimia corymbifera (formerly Absidia corymbifera) complex isolates associated with human mucormycosis: rehabilitation of L. ramosa. J. Clin. Microbiol. 47, 3862–3870 (2009).
  Medline CASGoogle Scholar
• 44 Schrödl W, Heydel T, Schwartze VU et al. Direct analysis and identification of pathogenic Lichtheimia species by matrix-assisted laser desorption ionization ‘Time of Flight’ analyzer-mediated mass spectrometry. J. Clin. Microbiol. 50, 419–427(2012).
  MedlineGoogle Scholar
• 45 De Carolis E, Posteraro B, Lass-Flörl C et al. Species identification of Aspergillus, Fusarium and Mucorales with direct surface analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin. Microbiol. Infect. 18, 475–484 (2012).
  Medline CASGoogle Scholar
• 46 Pickering JW, Sant HW, Bowles CAP, Roberts WL, Woods GL. Evaluation of a (1→3)-β-d-glucan assay for diagnosis of invasive fungal infections. J. Clin. Microbiol. 43, 5957–5962 (2005).
  Medline CASGoogle Scholar
• 47 Sandven PER, Eduard W. Detection and quantitation of antibodies against Rhizopus by enzyme-linked immunosorbent assay. APMIS 100, 981–987 (1992).
  Medline CASGoogle Scholar
• 48 Ashikari T, Nakamura N, Tanaka Y et al. Rhizopus raw-starch-degrading glucoamylase: its cloning and expression in yeast. Agric. Biol. Chem. 50, 957–964 (1986).
  CASGoogle Scholar
• 49 Zhang Q, Li M, Ma H, Sun Y, Xing L. Identification and characterization of a novel delta 6-fatty acid desaturase gene from Rhizopus arrhizus. FEBS Lett. 556, 81–85 (2004).
  Medline CASGoogle Scholar
• 50 Wysong DR, Waldorf AR. Electrophoretic and immunoblot analyses of Rhizopus arrhizus antigens. J. Clin. Microbiol. 25, 358–363 (1987).
  Medline CASGoogle Scholar
• 51 Jones KW, Kaufman L. Development and evaluation of an immunodiffusion test for diagnosis of systemic zygomycosis (mucormycosis): preliminary report. Clin. Microbiol. 7, 97–101 (1978).
  CASGoogle Scholar
• 52 Mackenzie DWR, Soothill JF, Millar JHD. Meningitis caused by Absidia corymbifera. J. Infect. 17, 241–248 (1988).
  Medline CASGoogle Scholar
• 53 Kaufman L, Turner LF, McLaughlin DW. Indirect enzyme-linked immunosorbent assay for zygomycosis. J. Clin. Microbiol. 27, 1979–1982 (1989).
  Medline CASGoogle Scholar
• 54 Jensen HE, Salonen J, Ekfors TO. The use of immunohistochemistry to improve sensitivity and specificity in the diagnosis of systemic mycoses in patients with haematological malignancies. J. Pathol. 181, 100–105 (1997).
  Medline CASGoogle Scholar
• 55 Jensen HE, Schonheyder HC, Hotchi M, Kaufman L. Diagnosis of systemic mycoses by specific immunohistochemical tests. APMIS 104, 241–258 (1996).
  Medline CASGoogle Scholar
• 56 Potenza L, Vallerini D, Barozzi P et al. Mucorales-specific T cells emerge in the course of invasive mucormycosis and may be used as a surrogate diagnostic marker in high-risk patients. Blood 118, 5416–5419 (2011).
  Medline CASGoogle Scholar
• 57 Hsiao CR, Huang L, Bouchara J-P, Barton R, Li HC, Chang TC. Identification of medically important molds by an oligonucleotide array. J. Clin. Microbiol. 43, 3760–3768 (2005).
  Medline CASGoogle Scholar
• 58 Nagao K, Ota T, Tanikawa A et al. Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene. J. Dermatol. Sci. 39, 23–31 (2005).
  Medline CASGoogle Scholar
• 59 Larché J, Machouart M, Burton K et al. Diagnosis of cutaneous mucormycosis due to Rhizopus microsporus by an innovative PCR-restriction fragment-length polymorphism method. Clin. Infect. Dis. 41, 1362–1365 (2005).
  Medline CASGoogle Scholar
• 60 Machouart M, Larché J, Burton K et al. Genetic identification of the main opportunistic mucorales by PCR-restriction fragment length polymorphism. J. Clin. Microbiol. 44, 805–810 (2006).
  Medline CASGoogle Scholar
• 61 Nyilasi I, Papp T, Csernetics Á, Krizsán K, Nagy E, Vágvölgyi C. High-affinity iron permease (FTR1) gene sequence-based molecular identification of clinically important Zygomycetes. Clin. Microbiol. Infect. 14, 393–397 (2008).
  Medline CASGoogle Scholar
• 62 Kasai M, Harrington SM, Francesconi A et al. Detection of a molecular biomarker for zygomycetes by quantitative PCR assays of plasma, bronchoalveolar lavage, and lung tissue in a rabbit model of experimental pulmonary zygomycosis. J. Clin. Microbiol. 46, 3690–3702 (2008).• First description of the systematic application of a quantitative PCR assay for the detection of circulating Zygomycete-specific DNA in plasma/bronchoalveolar lavage. The authors were able to isolate zygomycete-specific DNA in bronchoalveolar lavage and plasma of pulmonary infected rabbits.
  Medline CASGoogle Scholar
• 63 Skiada A, Lanternier F, Groll AH et al. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3). Haematologica 98, 492–504 (2013).•• Comprehensive guideline on diagnosis and treatment of mucormycosis.
  Medline CASGoogle Scholar
• 64 Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin. Microbiol. Rev. 15, 465–484 (2002).
  MedlineGoogle Scholar
• 65 Consortium for the Barcode of Life (CBOL).www.barcoding.si.edu
  Google Scholar
• 66 Rickerts V, McCormick Smith I, Mousset S, Kommedal O, Fredricks DN. Deciphering the aetiology of a mixed fungal infection by broad-range PCR with sequencing and fluorescence in situ hybridisation. Mycoses 56, 681–686 (2013).
  Medline CASGoogle Scholar
• 67 Miller MB, Tang YW. Basic concepts of microarrays and potential applications in clinicalmicrobiology. Clin. Microbiol. Rev. 22, 611–633 (2009).
  Medline CASGoogle Scholar
• 68 Chakrabarti A, Ghosh A, Prasad GS et al. Apophysomyces elegans: an emerging zygomycete in India. J. Clin. Microbiol. 41, 783–788 (2003).
  Medline CASGoogle Scholar
• 69 Schwarz P, Bretagne S, Gantier J-C et al. Molecular identification of zygomycetes from culture and experimentally infected tissues. J. Clin. Microbiol. 44, 340–349 (2006).
  Medline CASGoogle Scholar
• 70 Dannaoui E, Schwarz P, Slany M et al. Molecular detection and identification of zygomycetes species from paraffin-embedded tissues in a murine model of disseminated zygomycosis: a collaborative European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) evaluation. J. Cliln. Microbiol. 48, 2043–2046 (2010).
  Medline CASGoogle Scholar
• 71 Bialek R, Konrad F, Kern J et al. PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue. J. Clin. Pathol. 58, 1180–1184 (2005).
  Medline CASGoogle Scholar
• 72 Hata DJ, Buckwalter SP, Pritt BS, Roberts GD, Wengenack NL. Real-time PCR method for detection of zygomycetes. J. Clin. Microbiol. 46(7), 2353–2358 (2008).
  Medline CASGoogle Scholar
• 73 Bernal-Martínez L, Buitrago MJ, Castelli MV, Rodriguez-Tudela JL, Cuenca-Estrella M. Development of a single tube multiplex real-time PCR to detect the most clinically relevant Mucormycetes species. Clin. Microbiol. Infect. 19, E1–E7 (2012).
  MedlineGoogle Scholar
• 74 Millon L, Larosa F, Lepiller Q et al. Quantitative polymerase chain reaction detection of circulating DNA in serum for early diagnosis of mucormycosis in immunocompromised patients. Clin. Infect. Dis. 56, e95–e101 (2013).• This study proved that quantitative PCR can be used as a screening tool in high-risk patients. Nine out of ten patients are found to be positive between 68 and 3 days before mucormycosis was confirmed with histopathological examination.
  Medline CASGoogle Scholar
• 75 Tietz HJ, Brehmer D, Jänisch W, Martin H. [Occurrence of endomycoses in autopsy material of Berlin Charitè.] Mycoses 41, 81–85 (1998).
  MedlineGoogle Scholar
• 76 Hrncirova K, Lengerova M, Kocmanova I et al. Rapid detection and identification of mucormycetes from culture and tissue samples by use of high-resolution melt analysis. J. Clin. Microbiol. 48, 3392–3394 (2010).• A PCR reaction followed by high resolution melt curve analysis is represented that allows the discrimination of six different mucormycetes down to species-level in a single reaction.
  MedlineGoogle Scholar
• 77 El-Bouri K, Johnston S, Rees E et al. Comparison of bacterial identification by MALDI-TOF mass spectrometry and conventional diagnostic microbiology methods: agreement, speed and cost implications. Br. J. Biomed. Sci. 69, 47–55 (2012).
  Medline CASGoogle Scholar
• 78 Sendid B, Ducoroy P, François N et al. Evaluation of MALDI-TOF mass spectrometry for the identification of medically-important yeasts in the clinical laboratories of Dijon and Lille hospitals. Med. Mycol. 51, 25–32 (2012).
  MedlineGoogle Scholar
• 79 van Veen SQ, Claas EC, Kuijper EJ. High-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories. J. Clin. Microbiol. 48, 900–907 (2010).
  Medline CASGoogle Scholar
• 80 Dhiman N, Hall L, Wohlfiel SL, Buckwalter SP, Wengenack NL. Performance and cost analysis of matrix-assisted laser desorption ionization – Time of Flight mass spectrometry for routine identification of yeast. J. Clin. Microbiol. 49, 1614–1616 (2011).
  Medline CASGoogle Scholar
• 81 Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL. GenBank. Nucleic Acids Res. 36(Database issue), D25–D30 (2008).
  Medline CASGoogle Scholar
• 82 O’Donnell K, Cigelnik E. Two divergent intragenomic rDNA ITS2 types within a monophyletic lineage of the fungus Fusarium are nonorthologous. Mol. Phylogenet. Evol. 7, 103–116 (1997).
  MedlineGoogle Scholar
• 83 Okabe I, Arakawa M, Matsumoto N. ITS polymorphism within a single strain of Sclerotium rolfsii. Mycoscience 42, 107–113 (2001).
  CASGoogle Scholar
• 84 Nilsson RH, Ryberg M, Kristiansson E, Abarenkov K, Larsson K-H, Kõljalg U. Taxonomic reliability of DNA sequences in public sequence databases: a fungal perspective. PLoS ONE 1, e59 (2006).
  MedlineGoogle Scholar
• 85 Chakrabarti A, Prasad GS, Surname FN et al. Apophysomyces elegans: an emerging zygomycete in India. J. Clin. Microbiol. 41(2), 783–788 (2003).
  MedlineGoogle Scholar