, Volume 182, Issue 3–4, pp 297–303 | Cite as

Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria infectoria in a Heart Transplant Recipient

  • Pavlina Lyskova
  • Milos Kubanek
  • Vit Hubka
  • Eva Sticova
  • Ludek Voska
  • Dana Kautznerova
  • Miroslav Kolarik
  • Petr Hamal
  • Martina Vasakova


We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61-year-old heart transplant recipient with multiple skin lesions and pulmonary infiltrates. The infection spread via the haematogenous route from the primary cutaneous lesions into the lungs. The diagnosis was based on the histopathological examination, direct microscopy, skin lesion cultures and detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular methods. The treatment consisted of a combination of surgical excision and systemic antifungal therapy. Voriconazole was the first agent used but had a weak effect. Posaconazole was subsequently used to achieve a successful response. The isolate was identified as A. infectoria by sequencing of the rDNA ITS region and the partial β-tubulin gene.


Heart transplantation Phaeohyphomycosis Pulmonary infection Alternariosis 



This research was supported by the Ministry of Education, Youth and Sports of the Czech Republic (SVV project), and by the project “BIOCEV—Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” (CZ.1.05/1.1.00/02.0109) from the European Regional Development Fund. Additional support was obtained from a research grant from the Ministry of Health, Czech Republic [MZ 15-27682A] and from the project of the Ministry of Health, Czech Republic, for development of research organization 00023001 (IKEM, Prague, Czech Republic). This work was also supported by grant no. IGA_LF_2016_022 and RVO: 61989592 (Palacky University Olomouc, Czech Republic). All rights reserved.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Pagano L, Offidani M, Fianchi L, Nosari A, Candoni M, Piccardi M, Corvatta L, D’antonio D, Girmenia C, Martino P, Del Favero A. Mucormycosis in hematologic patients. Haematologica. 2004;89:207–14.PubMedGoogle Scholar
  2. 2.
    Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestation of mucormycosis. Clin Infect Dis. 2012;54:S23–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Revankar SG. Phaeohyphomycosis in transplant patients. J Fungi. 2015;2:2.CrossRefGoogle Scholar
  4. 4.
    Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Microbiol Rev. 2010;23:884–928.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mirhendi H, Fatemi MJ, Bateni H, Hajabdolbaghi M, Geramishoar M, Ahmadi B, Badali H. First case of disseminated phaeohyphomycosis in an immunocompetent individual due to Alternaria malorum. Med Mycol. 2013;51:196–202.CrossRefPubMedGoogle Scholar
  6. 6.
    Schieffelin JS, Garcia-Diaz JB, Loss GE, Beckman EN, Keller RA, Staffeld-Coit C, Garces JC, Pankey GA. Phaeohyphomycosis fungal infections in solid organ transplant recipients: clinical presentation, pathology, and treatment. Transpl Infect Dis. 2014;16:270–8.CrossRefPubMedGoogle Scholar
  7. 7.
    McCarty TP, Baddley JW, Walsh TJ, Alexander BD, Kontoyiannis DP, Perl TM, Walker R, Patterson TF, Schuster MG, Lyon GM, Wingard JR, Andes DR, Park BJ, Brandt ME, Pappas PG. Phaeohyphomycosis in transplant recipients: results from the Transplant Associated Infection Surveillance Network (TRANSNET). Med Mycol. 2015;53:440–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Pastor FJ, Guarro J. Alternaria infections: laboratory diagnosis and relevant clinical features. Clin Microbiol Infect. 2008;14:734–46.CrossRefPubMedGoogle Scholar
  9. 9.
    Thomma BP. Alternaria spp.: from general saprophyte to specific parasit. Mol Plant Pathol. 2003;4:225–36.CrossRefPubMedGoogle Scholar
  10. 10.
    Revankar SG, Petterson JE, Sutton DA, Pullen R, Rinaldi MG. Disseminated phaeohyphomycosis: rewiew of an emerging mycosis. Clin Infect Dis. 2002;34:467–76.CrossRefPubMedGoogle Scholar
  11. 11.
    Chowdhary A, Meis JF, Guarro J, Hoog GD, Kathuria S, Arendrup MC, Arikan-Akdagli S, Akova M, Boekhout T, Caira M, Guinea J, Chakrabarti A, Dannaoui E, van Diepeningen A, Freiberger T, Groll AH, Hope WW, Johnson E, Lackner M, Lagrou K, Lanternier F, Lass-Flörl C, Lortholary O, Meletiadis J, Muñoz P, Pagano L, Petrikkos G, Richardson MD, Roilides E, Skiada A, Tortorano AM, Ullmann AJ, Verweij PE, Cornely OA, Cuenca-Estrella M. ESCMID and ECMM joint clinical guidelines for the diagnosis and management of systemic phaeohyphomycosis: diseases caused by black fungi. Clin Microbiol Infect. 2014;20:47–75.CrossRefPubMedGoogle Scholar
  12. 12.
    Secnikova Z, Juzlova K, Vojackova N, Kazakov DV, Hoskova L, Fialova J, Dzambova M, Hercogova J. The rare case of Alternaria alternata cutaneous and pulmonary infection in a heart transplant recipient treated by azole antifungals. Dermatol Ther. 2014;27:140–3.CrossRefPubMedGoogle Scholar
  13. 13.
    Espinel-Ingroff A, Canton E. Comparison of Neo-Sensitabs tablet diffusion assay with CLSI broth microdilution M38-A and disk diffusion methods for testing susceptibility of filamentous fungi with Amphotericin B, Caspofungin, Itraconazole, Posaconazole, and Voriconazole. J Clin Microbiol. 2008;46:1793–803.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hubka V, Novakova A, Peterson SW, Frisvad JC, Sklenar F, Matsuzawa T, Kubatova A, Kolarik M. A reappraisal of Aspergillus section Nidulantes with descriptions of two new sterigmatocystin producing species. Plant Syst Evol. 2016;. doi: 10.1007/s00606-016-1331-5.Google Scholar
  15. 15.
    Hubka V, Lyskova P, Frisvad JC, Peterson SW, Skorepova M, Kolarik M. Aspergillus pragensis sp. nov. discovered during molecular re-identification of clinical isolates belonging to Aspergillus section Candidi. Med Mycol. 2014;52:565–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Derber C, Elam K, Bearman G. Invasive sinonasal disease due to dematiaceous fungi in immunocompromised individuals: case report and review of the literature. Int J Infect Dis. 2010;14:e329–32.CrossRefPubMedGoogle Scholar
  17. 17.
    Salido-Vallejo R, Linares-Sicilia MJ, Garnacho-Saucedo G, Sánchez-Frías M, Solís-Cuesta F, Gené J, Moreno-Giménez JC. Subcutaneous phaeohyphomycosis due to Alternaria infectoria in a renal transplant patient: surgical treatment with no long-term relapse. Rev Iberoam Micol. 2014;31:149–51.CrossRefPubMedGoogle Scholar
  18. 18.
    Segner S, Jouret F, Durant JF, Marot L, Kanaan N. Cutaneous infection by Alternaria infectoria in a renal transplant patient. Transpl Infect Dis. 2009;11:330–2.CrossRefPubMedGoogle Scholar
  19. 19.
    Gallelli B, Viviani M, Nebuloni M, Marzano AV, Pozzi C, Messa P, Fogazzi GB. Skin infection due to Alternaria species in kidney allograft recipients: report of a new case and review of the literature. J Nephrol. 2006;19:668–72.PubMedGoogle Scholar
  20. 20.
    Vermeire SE, de Jonge H, Lagrou K, Kuypers DR. Cutaneous phaeohyphomycosis in renal allograft recipients: report of 2 cases and review of the literature. Diagn Microbiol Infect Dis. 2010;68:177–80.CrossRefPubMedGoogle Scholar
  21. 21.
    González-Vela MC, Armesto S, Unda-Villafuerte F, Val-Bernal JF. Cutaneous infection with Alternaria triticina in a bilateral lung transplant recipient. Actas Dermo-Sifiliogr. 2014;105:e51–4.CrossRefGoogle Scholar
  22. 22.
    Boyce RD, Deziel PJ, Otley CC, Wilhelm MP, Eid AJ, Wengenack NL, Razonable RR. Phaeohyphomycosis due to Alternaria species in transplant recipients. Transpl Infect Dis. 2010;12:242–50.CrossRefPubMedGoogle Scholar
  23. 23.
    de Sousa Ferreira I, Teixeira G, Abecasis M. Alternaria alternata invasive fungal infection in a patient with Fanconi’s Anemia after an unrelated bone marrow transplant. Clin Drug Investig. 2013;33:33–6.CrossRefGoogle Scholar
  24. 24.
    Hipolito E, Faria E, Alves AF, De Hoog GS, Anjos J, Gonçalves T, Morais PV, Estevão H. Alternaria infectoria brain abscess in a child with chronic granulomatous disease. Eur J Clin Microbiol Infect Dis. 2009;28:377–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Halaby T, Boots H, Vermeulen A, Ven A, Beguin H, Hooff H, Jacobs J. Phaeomycosis caused by Alternaria infectoria in a renal transplant recipient. J Clin Microbiol. 2001;39:1953–5.CrossRefGoogle Scholar
  26. 26.
    Tomasini C. Septic vasculitis and vasculopathy in some infectious emergencies: the perspective of the histopathologist. G ital di dermatol e venereol organo uff Soc ital di dermatol e sifilogr. 2015;150:73–85.Google Scholar
  27. 27.
    Shoham S. Emerging fungal infections in solid organ transplant recipients. Infect Dis Clin North Am. 2013;27:305–16.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    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, Pappasa PG. 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. 2010;50:1091–100.CrossRefPubMedGoogle Scholar
  29. 29.
    Woudenberg JHC, Groenewald JZ, Binder M, Crous PW. Alternaria redefined. Stud Mycol. 2013;175:171–212.CrossRefGoogle Scholar
  30. 30.
    Andersen B, Sørensen JL, Nielsen KF, van den Ende BG, de Hoog S. A polyphasic approach to the taxonomy of the Alternaria infectoria species-group. Fungal Genet Biol. 2009;46:642–56.CrossRefPubMedGoogle Scholar
  31. 31.
    Lawrence DP, Gannibal PB, Peever TL, Pryor BM. The sections of Alternaria: formalizing species-group concepts. Mycologia. 2013;105:530–46.CrossRefPubMedGoogle Scholar
  32. 32.
    Woudenberg JHC, Seidl MF, Groenewald JZ, de Vries M, Stielow JB, Thomma BPHJ, Crous PW. Alternaria section Alternaria: species, formae speciales or pathotypes? Stud Mycol. 2015;82:1–21.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cuétara MS, Alhambra A, Moragues MD, González-Elorza E, Pontón J, del Palacio A. Detection of (1 → 3)-β-D-glucan as an adjunct to diagnosis in a mixed population with uncommon proven invasive fungal diseases or with an unusual clinical presentation. Clin Vaccine Immunol. 2009;16:423–6.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Kpodzo DS, Calderwood MS, Ruchelsman DE, Abramson JS, Piris A, Winograd JM, Kotton CN. Primary subcutaneous Alternaria alternata infection of the hand in an immunocompromised host. Med Mycol. 2011;49:543–7.PubMedGoogle Scholar
  35. 35.
    Miele PS, Levy CS, Smith MA, Dugan EM, Cooke RH, Light JA, Lucey DR. Primary cutaneous fungal infections in solid organ transplantation: a case series. Am J Transplant. 2002;2:678–83.CrossRefPubMedGoogle Scholar
  36. 36.
    Brás S, Sabino R, Laureano A, Simões H, Fernandes C, Marques-Pinto G, Cardoso J, Veríssimo C. Cutaneous infection by different Alternaria species in a liver transplant recipient. Med Mycol Case Rep. 2015;8:1–4.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Badali H, de Hoog GS, Curfs-Breuker I, Meis JF. In vitro activities of eight antifungal drugs against 70 clinical and environmental isolates of Alternaria species. J Antimicrob Chemother. 2009;63:1295–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Alastruey-Izquierdo A, Cuesta I, Ros L, Mellado E, Rodriguez-Tudela JL. Antifungal susceptibility profile of clinical Alternaria spp. identified by molecular methods. J Antimicrob Chemother. 2011;66:2585–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Rammaert B, Aguilar C, Bougnoux ME, Noël N, Charlier C, Denis B, Lecuit M, Lortholary O. Success of posaconazole therapy in a heart transplanted patient with Alternaria infectoria cutaneous infection. Med Mycol. 2012;50:518–21.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Laboratory of Medical Mycology, Department of Parasitology, Mycology and Mycobacteriology PraguePublic Health Institute in Usti nad LabemPrague 8Czech Republic
  2. 2.Department of Microbiology, Faculty of Medicine and DentistryPalacky University, OlomoucOlomoucCzech Republic
  3. 3.Department of CardiologyInstitute for Clinical and Experimental MedicinePrague 4Czech Republic
  4. 4.Department of Botany, Faculty of ScienceCharles University in PraguePrague 2Czech Republic
  5. 5.Laboratory of Fungal MetabolismInstitute of Microbiology of the AS CRPrague 4Czech Republic
  6. 6.Department of PathologyInstitute for Clinical and Experimental MedicinePrague 4Czech Republic
  7. 7.Department of Diagnostic and Interventional RadiologyInstitute for Clinical and Experimental MedicinePrague 4Czech Republic
  8. 8.Department of Respiratory Medicine, Thomayer Hospital1st Medical School and Charles UniversityPrague 4Czech Republic

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