, Volume 182, Issue 3–4, pp 305–313 | Cite as

In Vitro Antifungal Susceptibility of Neoscytalidium dimidiatum Clinical Isolates from Malaysia

  • Jasper Elvin James
  • Jacinta Santhanam
  • Mei Chen Lee
  • Choon Xian Wong
  • Parameswari Sabaratnam
  • Hamidah Yusoff
  • Mohd Nizam Tzar
  • Mohd Fuat Abdul Razak


Neoscytalidium dimidiatum is an opportunistic fungus causing cutaneous infections mostly, which are difficult to treat due to antifungal resistance. In Malaysia, N. dimidiatum is associated with skin and nail infections, especially in the elderly. These infections may be mistaken for dermatophyte infections due to similar clinical appearance. In this study, Neoscytalidium isolates from cutaneous specimens, identified using morphological and molecular methods (28 Neoscytalidium dimidiatum and 1 Neoscytalidium sp.), were evaluated for susceptibility towards antifungal agents using the CLSI broth microdilution (M38-A2) and Etest methods. Amphotericin B, voriconazole, miconazole and clotrimazole showed high in vitro activity against all isolates with MIC ranging from 0.0313 to 1 µg/mL. Susceptibility towards fluconazole and itraconazole was noted in up to 10% of isolates, while ketoconazole was inactive against all isolates. Clinical breakpoints for antifungal drugs are not yet available for most filamentous fungi, including Neoscytalidium species. However, the results indicate that clinical isolates of N. dimidiatum in Malaysia were sensitive towards miconazole, clotrimazole, voriconazole and amphotericin B, in vitro.


Neoscytalidium dimidiatum Antifungal susceptibility Malaysia 



We would like to thank Pharmaniaga (Malaysia) for providing antifungal agents for this study. This work was fully funded by a Research University Grant UKM-GUP-2011-118 from Universiti Kebangsaan Malaysia.

Compliance with ethical standards

This study is in compliance with institutional ethical requirements of Universiti Kebangsaan Malaysia.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Havlickova B, Czaika VA, Friedrich M. Epidemiological trends in skin mycoses worldwide. Mycoses. 2008;51(Suppl 4):2–15. doi: 10.1111/j.1439-0507.2008.01606.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Crous PW, Slippers B, Wingfield MJ, Rheeder J, Marasas WF, Philips AJ, et al. Phylogenetic lineages in the Botryosphaeriaceae. Stud Mycol. 2006;55:235–53.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gentles JC, Evans EG. Infection of the feet and nails with Hendersonula toruloidea. Sabouraudia. 1970;8(1):72–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Bunyaratavej S, Prasertworonun N, Leeyaphan C, Chaiwanon O, Muanprasat C, Matthapan L. Distinct characteristics of Scytalidium dimidiatum and non-dermatophyte onychomycosis as compared with dermatophyte onychomycosis. J Dermatol. 2015;. doi: 10.1111/1346-8138.12768.PubMedGoogle Scholar
  5. 5.
    Arrese JE, Pierard-Franchimont C, Pierard GE. Scytalidium dimidiatum melanonychia and scaly plantar skin in four patients from the Maghreb: imported disease or outbreak in a Belgian mosque? Dermatology. 2001;202(2):183–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Moore MK. Skin and nail infections by non-dermatophytic filamentous fungi. Mykosen Suppl. 1978;1:128–32.PubMedGoogle Scholar
  7. 7.
    Oyeka CA, Okoli I. Isolation of dermatophytes and non-dermatophytic fungi from soil in Nigeria. Mycoses. 2003;46(8):336–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Menotti J, Machouart M, Benderdouche M, Cetre-Sossah C, Morel P, Dubertret L, et al. Polymerase chain reaction for diagnosis of dermatophyte and Scytalidium spp. onychomycosis. Br J Dermatol. 2004;151(2):518–9. doi: 10.1111/j.1365-2133.2004.06089.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Elinav H, Izhar U, Benenson S, Admon D, Hidalgo-Grass C, Polacheck I, et al. Invasive Scytalidium dimidiatum infection in an immunocompetent adult. J Clin Microbiol. 2009;47(4):1259–63. doi: 10.1128/JCM.01874-08.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hariri A, Choudhury N, Saleh HA. Scytalidium dimidiatum associated invasive fungal sinusitis in an immunocompetent patient. J Laryngol Otol. 2014;128(11):1018–21. doi: 10.1017/S002221511400214X.CrossRefPubMedGoogle Scholar
  11. 11.
    Ng KP, Saw TL, Madasamy M, Soo Hoo T. Onychomycosis in Malaysia. Mycopathologia. 1999;147(1):29–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Ungpakorn R. Mycoses in Thailand: current concerns. Jpn J Med Mycol. 2005;46(2):81–6.CrossRefGoogle Scholar
  13. 13.
    Lacroix C, de Chauvin MF. In vitro activity of amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and terbinafine against Scytalidium dimidiatum and Scytalidium hyalinum clinical isolates. J Antimicrob Chemother. 2008;61(4):835–7. doi: 10.1093/jac/dkn011.CrossRefPubMedGoogle Scholar
  14. 14.
    Madrid H, Ruiz-Cendoya M, Cano J, Stchigel A, Orofino R, Guarro J. Genotyping and in vitro antifungal susceptibility of Neoscytalidium dimidiatum isolates from different origins. Int J Antimicrob Agents. 2009;34(4):351–4. doi: 10.1016/j.ijantimicag.2009.05.006.CrossRefPubMedGoogle Scholar
  15. 15.
    Bueno JG, Martinez C, Zapata B, Sanclemente G, Gallego M, Mesa AC. In vitro activity of fluconazole, itraconazole, voriconazole and terbinafine against fungi causing onychomycosis. Clin Exp Dermatol. 2010;35(6):658–63. doi: 10.1111/j.1365-2230.2009.03698.x.CrossRefPubMedGoogle Scholar
  16. 16.
    Messer SA, Diekema DJ, Hollis RJ, Boyken LB, Tendolkar S, Kroeger J, et al. Evaluation of disk diffusion and Etest compared to broth microdilution for antifungal susceptibility testing of posaconazole against clinical isolates of filamentous fungi. J Clin Microbiol. 2007;45(4):1322–4. doi: 10.1128/JCM.02450-06.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    European Committee on Antimicrobial Susceptibility Testing, Breakpoint tables for interpretation of MICs, Version 7.0. 2014. Accessed 24 January 2015.
  18. 18.
    de Hoog GS, Guarro J, Gené J, Figueras MJ. Atlas of clinical fungi. Utrecht: Centraalbureau voor Schimmelcultures; 2000.Google Scholar
  19. 19.
    Yazdanparast SA, Barton RC. Arthroconidia production in Trichophyton rubrum and a new ex vivo model of onychomycosis. J Med Microbiol. 2006;55(Pt 11):1577–81. doi: 10.1099/jmm.0.46474-0.CrossRefPubMedGoogle Scholar
  20. 20.
    Oycka CA, Gugnani HC. Keratin degradation by Scytalidium species and Fusarium solani. Mycoses. 1998;41(1–2):73–6.CrossRefPubMedGoogle Scholar
  21. 21.
    Marriott DJ, Wong KH, Aznar E, Harkness JL, Cooper DA, Muir D. Scytalidium dimidiatum and Lecythophora hoffmannii: unusual causes of fungal infections in a patient with AIDS. J Clin Microbiol. 1997;35(11):2949–52.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Sigler L, Summerbell RC, Poole L, Wieden M, Sutton DA, Rinaldi MG, et al. Invasive Nattrassia mangiferae infections: case report, literature review, and therapeutic and taxonomic appraisal. J Clin Microbiol. 1997;35(2):433–40.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Lacaz CS, Pereira AD, Heins-Vaccari EM, Cuce LC, Benatti C, Nunes RS, et al. Onychomycosis caused by Scytalidium dimidiatum. Report of two cases. Review of the taxonomy of the synanamorph and anamorph forms of this coelomycete. Rev Inst Med Trop Sao Paulo. 1999;41(5):319–23.PubMedGoogle Scholar
  24. 24.
    Roeijmans HJ, De Hoog GS, Tan CS, Figge MJ. Molecular taxonomy and GC/MS of metabolites of Scytalidium hyalinum and Nattrassia mangiferae (Hendersonula toruloidea). J Med Vet Mycol. 1997;35(3):181–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Morris-Jones R, Youngchim S, Hextall JM, Gomez BL, Morris-Jones SD, Hay RJ, et al. Scytalidium dimidiatum causing recalcitrant subcutaneous lesions produces melanin. J Clin Microbiol. 2004;42(8):3789–94. doi: 10.1128/JCM.42.8.3789-3794.2004.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Hay RJ. Scytalidium infections. Curr Opin Infect Dis. 2002;15(2):99–100.CrossRefPubMedGoogle Scholar
  27. 27.
    van Duin D, Casadevall A, Nosanchuk JD. Melanization of Cryptococcus neoformans and Histoplasma capsulatum reduces their susceptibilities to amphotericin B and caspofungin. Antimicrob Agents Chemother. 2002;46(11):3394–400.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ikeda R, Sugita T, Jacobson ES, Shinoda T. Effects of melanin upon susceptibility of Cryptococcus to antifungals. Microbiol Immunol. 2003;47(4):271–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Kondori N, Svensson E, Mattsby-Baltzer I. In vitro susceptibility of filamentous fungi to itraconazole, voriconazole and posaconazole by Clinical and Laboratory Standards Institute reference method and E-test. Mycoses. 2011;54(5):e318–22. doi: 10.1111/j.1439-0507.2010.01913.x.CrossRefPubMedGoogle Scholar
  30. 30.
    Espinel-Ingroff A, Rezusta A. E-test method for testing susceptibilities of Aspergillus spp. to the new triazoles voriconazole and posaconazole and to established antifungal agents: comparison with NCCLS broth microdilution method. J Clin Microbiol. 2002;40(6):2101–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tortorano AM, Prigitano A, Esposto MC, Arsic Arsenijevic V, Kolarovic J, Ivanovic D, et al. European Confederation of Medical Mycology (ECMM) epidemiological survey on invasive infections due to Fusarium species in Europe. Eur J Clin Microbiol Infect Dis. 2014;. doi: 10.1007/s10096-014-2111-1.PubMedGoogle Scholar
  32. 32.
    Elinav H, Izhar U, Benenson S, Admon D, Hidalgo-Grass C, Polacheck I, et al. Invasive Scytalidium dimidiatum infection in an immunocompetent adult. J Clin Microbiol. 2009;47(4):1259–63. doi: 10.1128/JCM.01874-08.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Yew SM, Chan CL, Lee KW, Na SL, Tan R, Hoh CC, et al. A five-year survey of dematiaceous fungi in a tropical hospital reveals potential opportunistic species. PLoS ONE. 2014;9(8):e104352. doi: 10.1371/journal.pone.0104352.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Garinet S, Tourret J, Barete S, Arzouk N, Meyer I, Frances C, et al. Invasive cutaneous Neoscytalidium infections in renal transplant recipients: a series of five cases. BMC Infect Dis. 2015;15:535. doi: 10.1186/s12879-015-1241-0.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Spriet I, Lambrecht C, Lagrou K, Verhamme B. Successful eradication of Scytalidium dimidiatum-induced ungual and cutaneous infection with voriconazole. Eur J Dermatol. 2012;22(2):197–9. doi: 10.1684/ejd.2011.1616.PubMedGoogle Scholar
  36. 36.
    Benne CA, Neeleman C, Bruin M, de Hoog GS, Fleer A. Disseminating infection with Scytalidium dimidiatum in a granulocytopenic child. Eur J Clin Microbiol Infect Dis. 1993;12(2):118–21.CrossRefPubMedGoogle Scholar
  37. 37.
    Guarro J, Pujol I, Aguilar C, Ortoneda M. In vitro antifungal susceptibility of nondermatophytic keratinophilic fungi. Revista Iberoamericana de Micologia. 2000:142–147.Google Scholar
  38. 38.
    Khan ZU, Ahmad S, Joseph L, Chandy R. Cutaneous phaeohyphomycosis due to Neoscytalidium dimidiatum: first case report from Kuwait. J Mycol Med. 2009;19(2):138–42. doi: 10.1016/j.mycmed.2009.02.005.CrossRefGoogle Scholar
  39. 39.
    Oyeka CA, Gugnani HC. Isoconazole nitrate versus clotrimazole in foot and nail infections due to Hendersonula toruloidea, Scytalidium hyalinum and dermatophytes. Mycoses. 1992;35(11–12):357–61.PubMedGoogle Scholar
  40. 40.
    Moore MK, del Palacio-Hernanz AD, Lopez-Gomez S. Scytalidium hyalinum infection diagnosed in Spain. Sabouraudia. 1984;22(3):243–5.CrossRefPubMedGoogle Scholar
  41. 41.
    Santhanam J, Nazmiah N, Aziz MN. Species distribution and antifungal susceptibility patterns of Candida species: is low susceptibility to itraconazole a trend in Malaysia? Med J Malays. 2013;68(4):343–7.Google Scholar
  42. 42.
    Levi ME, Smith JW. Posttraumatic infection due to Scytalidium dimidiatum. Clin Infect Dis. 1994;18(1):127–8.CrossRefPubMedGoogle Scholar
  43. 43.
    Hay RJ. Ketoconazole in the treatment of fungal infection. Clinical and laboratory studies. Am J Med. 1983;74(1B):16–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Aamir S, Aman S, Haroon T. Mycetoma caused by Scytalidium dimidiatum. Br J Dermatol. 2003;148(1):174–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Gumbo T, Mkanganwi N, Robertson VJ, Masvaire P. Case report. Nattrassia mangiferae endophthalmitis. Mycoses. 2002;45(3–4):118–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Grau S, Pozo J, Roma E, Salavert M, Barrueta J, Peral C, et al. Pharmacoeconomic analysis of anidulafungin, micafungin, caspofungin and fluconazole in the treatment of candidemia and/or invasive candidiasis in non-neutropenic adult patients In Spain. Value Health. 2015;18(7):A584–5. doi: 10.1016/j.jval.2015.09.1961.CrossRefPubMedGoogle Scholar
  47. 47.
    Branco J, Silva AP, Silva RM, Silva-Dias A, Pina-Vaz C, Butler G, et al. Fluconazole and voriconazole resistance in Candida parapsilosis is conferred by gain-of-function mutations in MRR1 transcription factor gene. Antimicrob Agents Chemother. 2015;59(10):6629–33. doi: 10.1128/AAC.00842-15.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Farjo QA, Farjo RS, Farjo AA. Scytalidium keratitis: case report in a human eye. Cornea. 2006;25(10):1231–3. doi: 10.1097/01.ico.0000230323.28956.b9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Jasper Elvin James
    • 1
  • Jacinta Santhanam
    • 1
  • Mei Chen Lee
    • 1
  • Choon Xian Wong
    • 1
  • Parameswari Sabaratnam
    • 2
  • Hamidah Yusoff
    • 3
  • Mohd Nizam Tzar
    • 3
  • Mohd Fuat Abdul Razak
    • 2
  1. 1.Biomedical Science Programme, Faculty of Health SciencesUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  2. 2.Bacteriology UnitInstitute for Medical ResearchKuala LumpurMalaysia
  3. 3.Department of Medical Microbiology and ImmunologyUniversiti Kebangsaan Malaysia Medical CentreCherasMalaysia

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