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Antifungal Activity of Antifungal Drugs, as Well as Drug Combinations Against Exophiala dermatitidis

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Abstract

To evaluate the in vitro efficacy of common antifungal drugs, as well as the interactions of caspofungin with voriconazole, amphotericin B, or itraconazole against the pathogenic black yeast Exophiala dermatitidis from China, the minimal inhibitory concentrations (MICs) of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against 16 strains of E. dermatitidis were determined by using CLSI broth microdilution method (M38-A2). The minimal fungicidal concentrations (MFCs) were also determined. Additionally, the interactions of caspofungin with voriconazole, amphotericin B, itraconazole or fluconazole, that of terbinafine with itraconazole, or that of fluconazole with amphotericin B were assessed by using the checkerboard technique. The fractional inhibitory concentration index (FICI) was used to categorize drug interactions as following, synergy, FICI ≤ 0.5; indifference, FICI > 0.5 and ≤4.0; or antagonism, FICI > 4.0. The MIC ranges of terbinafine, voriconazole, itraconazole, amphotericin B, fluconazole, and caspofungin against E. dermatitidis were 0.06–0.125 mg/l, 0.25–1.0 mg/l, 1.0–2.0 mg/l, 1.0–2.0 mg/l, 16–64 mg/l, and 32–64 mg/l, respectively. The in vitro interactions of caspofungin with voriconazole, amphotericin B, and itraconazole showed synergic effect against 10/16(62.5%), 15/16(93.75%), and 16/16(100%) isolates, while that of caspofungin with fluconazole showed indifference. Besides, the interaction of terbinafine with itraconazole as well as that of fluconazole with amphotericin B showed indifference. Terbinafine, voriconazole, itraconazole, and amphotericin B have good activity against E. dermatitidis. The combinations of caspofungin with voriconazole, amphotericin B or itraconazole present synergic activity against E. dermatitidis. These results provide the basis for novel options in treating various E. dermatitidis infections.

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References

  1. McGinnis MR. Chromoblastomycosis and phaeohyphomycosis: new concepts, diagnosis, and mycology. J Am Acad Dermatol. 1983;8:1–16.

    Article  CAS  PubMed  Google Scholar 

  2. Oztas E, Odemis B, Kekilli M, Kurt M, Dinc BM, Parlak E, et al. Systemic phaeohyphomycosis caused by Exophiala Dermatitidis resembling primary sclerosing cholangitis. J Med Microbiol. 2009;58:1243–6.

    Article  PubMed  Google Scholar 

  3. Alabaz D, Kibar F, Arikan S, Sancak B, Celik U, Aksaray N, et al. Systemic phaeohyphomycosis due to Exophiala (Wangiella) in an immunocompetent child. Med Mycol. 2009;31:1–5.

    Google Scholar 

  4. Hiruma M, Kawada A, Ohata H, Ohnishi Y, Takahashi H, Yamazaki M, et al. Systemic phaeohyphomycosis caused by Exophiala dermatitidis. Mycoses. 1993;36:1–7.

    Article  CAS  PubMed  Google Scholar 

  5. Li DM, de Hoog GS. Cerebral phaeohyphomycosis—a cure at what lengths? Lancet Infect Dis. 2009;9:376–83.

    Article  PubMed  Google Scholar 

  6. Chang X, Li R, Yu J, Bao X, Qin J. Phaeohyphomycosis of the central nervous system caused by Exophiala dermatitidis in a 3-year-old immunocompetent host. J Child Neurol. 2009;24:342–5.

    Article  PubMed  Google Scholar 

  7. Espinel-Ingroff A, Chaturvedi V, Fothergill A, Rinaldi MG. Optimal testing conditions for determining MICs and minimum fungicidal concentrations of new and established antifungal agents for uncommon molds: NCCLS collaborative study. J Clin Microbiol. 2002;40:3776–81.

    Article  CAS  PubMed  Google Scholar 

  8. Fothergill AW, Rinaldi MG, Sutton DA. Antifungal susceptibility testing of Exophiala spp.: a head-to-head comparison of amphotericin B, itraconazole, posaconazole and voriconazole. Med Mycol. 2009;47:41–3.

    Article  CAS  PubMed  Google Scholar 

  9. Okeke CN, Gugnani HC. In vitro sensitivity of environmental isolates of pathogenic dematiaceous fungi to azole compounds and a phenylpropyl-morpholine derivative. Mycopathologia. 1987;99:175–81.

    Article  CAS  PubMed  Google Scholar 

  10. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; Approved standard—M38-A2. CLSI, Wayne, PA, USA, 2008.

  11. Denning DW. Echinocandin antifungal drugs. Lancet. 2003;362:1142–51.

    Article  CAS  PubMed  Google Scholar 

  12. Sudhadham M, de Hoog GS, Menken SB, Gerrits VDEA, Sihanonth P. Rapid screening for genotypes as possible markers of virulence in the neurotropic black yeast Exophiala dermatitidis using PCR-RFLP. J Microbiol Methods. 2010;80:138–42.

    Article  CAS  PubMed  Google Scholar 

  13. Li DM, Li RY, de Hoog GS, Wang DL. Exophiala asiatica, a new species from patient with phaeohyphomycosis. Med Mycol. 2009;47:101–9.

    Article  CAS  PubMed  Google Scholar 

  14. Espinel-Ingroff A. In vitro fungicidal activities of voriconazole, itraconazole, and amphotericin B against opportunistic moniliaceous and dematiaceous fungi. J Clin Microbiol. 2001;39:954–8.

    Article  CAS  PubMed  Google Scholar 

  15. Odds FC. Synergy, antagonism, what the chequerboard puts between them. J Antimicrob Chemother. 2003;52:1.

    Article  CAS  PubMed  Google Scholar 

  16. Meletiadis J, Meis J, de Hoog GS, Verweij PE. In vitro susceptibilities of 11 clinical isolates of Exophiala species to six antifungal drugs. Mycoses. 2000;43:309–12.

    Article  CAS  PubMed  Google Scholar 

  17. Krishnan-Natesan S. Terbinafine: a pharmacological and clinical review. Expert Opin Pharmacother. 2009;10:2723–33.

    Article  CAS  PubMed  Google Scholar 

  18. Neoh CY, Tan SH, Perera P. Cutaneous phaeohyphomycosis due to Cladophialophora bantiana in an immunocompetent patient. Clin Exp Dermatol. 2007;32:539–40.

    Article  CAS  PubMed  Google Scholar 

  19. Revankar SG. Therapy of infections caused by dematiaceous fungi. Expert Rev Anti Infect Ther. 2005;3:601–12.

    Article  CAS  PubMed  Google Scholar 

  20. Meletiadis J, Mouton JW, Rodriguez-Tudela JL, Meis JF, Verweij PE. In vitro interaction of terbinafine with itraconazole against clinical isolates of Scedosporium prolificans. Antimicrob Agents Chemother. 2000;44:470–2.

    Article  CAS  PubMed  Google Scholar 

  21. Laniado-Laborin R, Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Rev Iberoam Micol. 2009;26:223–7.

    Article  PubMed  Google Scholar 

  22. Mukaino T, Koga T, Oshita Y, Narita Y, Obata S, Aizawa H. Exophiala dermatitidis infection in non-cystic fibrosis bronchiectasis. Respir Med. 2006;100:2069–71.

    Article  PubMed  Google Scholar 

  23. Petraitis V, Petraitiene R, Sarafandi AA, Kelaher AM, Lyman CA, Casler HE, et al. Combination therapy in treatment of experimental pulmonary aspergillosis: synergistic interaction between an antifungal triazole and an echinocandin. J Infect Dis. 2003;187:1834–43.

    Article  CAS  PubMed  Google Scholar 

  24. Aliff TB, Maslak PG, Jurcic JG, Heaney ML, Cathcart KN, Sepkowitz KA, et al. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer. 2003;97:1025–32.

    Article  CAS  PubMed  Google Scholar 

  25. Horre R, Schaal KP, Siekmeier R, Sterzik B, de Hoog GS, Schnitzler N. Isolation of fungi, especially Exophiala dermatitidis, in patients suffering from cystic fibrosis. A prospective study. Respiration. 2004;71:360–6.

    Article  CAS  PubMed  Google Scholar 

  26. Kusenbach G, Skopnik H, Haase G, Friedrichs F, Dohmen H. Exophiala dermatitidis pneumonia in cystic fibrosis. Eur J Pediatr. 1992;151:344–6.

    Article  CAS  PubMed  Google Scholar 

  27. Diemert D, Kunimoto D, Sand C, Rennie R. Sputum isolation of Wangiella dermatitidis in patients with cystic fibrosis. Scand J Infect Dis. 2001;33:777–9.

    Article  CAS  PubMed  Google Scholar 

  28. Espinel-Ingroff A. Mechanisms of resistance to antifungal agents: yeasts and filamentous fungi. Rev Iberoam Micol. 2008;25:101–6.

    Article  PubMed  Google Scholar 

  29. Hope WW, Billaud EM, Lestner J, Denning DW. Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis. 2008;21:580–6.

    Article  CAS  PubMed  Google Scholar 

  30. St-Germain G, Laverdiere M, Pelletier R, Rene P, Bourgault AM, Lemieux C, et al. Epidemiology and antifungal susceptibility of bloodstream Candida isolates in Quebec: report on 453 cases between 2003 and 2005. Can J Infect Dis Med Microbiol. 2008;19:55–62.

    PubMed  Google Scholar 

  31. Jain LR, Denning DW. The efficacy and tolerability of voriconazole in the treatment of chronic cavitary pulmonary aspergillosis. J Infect. 2006;52:133–7.

    Article  Google Scholar 

  32. Schwartz S, Ruhnke M, Ribaud P, Corey L, Driscoll T, Cornely OA, et al. Improved outcome in central nervous system aspergillosis, using voriconazole treatment. Blood. 2005;106:2641–5.

    Article  CAS  PubMed  Google Scholar 

  33. Cao C, Liu W, Li R, Wan Z, Qiao J. In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei. J Antimicrob Chemother. 2009;63:340–2.

    Article  CAS  PubMed  Google Scholar 

  34. O’Shaughnessy EM, Meletiadis J, Stergiopoulou T, et al. Antifungal interactions within the triple combination of amphotericin B, caspofungin and voriconazole against Aspergillus species. J Antimicrob Chemother. 2006;58:1168–76.

    Article  PubMed  Google Scholar 

  35. Kiraz N, Dag I, Yamac M, Demchok JP, Walsh TJ. Antifungal activity of caspofungin in combination with amphotericin B against Candida glabrata: comparison of disk diffusion, Etest, and time-kill methods. Antimicrob Agents Chemother. 2009;53:788–90.

    Article  CAS  PubMed  Google Scholar 

  36. Colombo AL, Rosas RC. Successful treatment of an Aspergillus brain abscess with caspofungin: case report of a diabetic patient intolerant of amphotericin B. Eur J Clin Microbiol Infect Dis. 2003;22:575–6.

    Article  CAS  PubMed  Google Scholar 

  37. Liu KH, Wu CJ, Chou CH, Lee HC, Lee NY, Hung ST, et al. Refractory candidal meningitis in an immunocompromised patient cured by caspofungin. J Clin Microbiol. 2004;42:5950–3.

    Article  PubMed  Google Scholar 

  38. Gubler C, Wildi SM, Imhof A, Schneemann M, Mullhaupt B. Disseminated invasive aspergillosis with cerebral involvement successfully treated with caspofungin and voriconazole. Infection. 2007;35:364–6.

    Article  CAS  PubMed  Google Scholar 

  39. Damaj G, Ivanov V, Le BB, D’incan E, Doglio MF, Bilger K, et al. Rapid improvement of disseminated aspergillosis with caspofungin/voriconazole combination in an adult leukemic patient. Ann Hematol. 2004;83:390–3.

    Article  CAS  PubMed  Google Scholar 

  40. Gea-Banacloche JC, Peter J, Bishop M, Kasten-Sportes C, Fowler D, et al. Successful treatment of invasive aspergillosis with the combination of voriconazole and caspofungin: correlation with in vitro interactions. Program and abstracts the 43rd Annual ICAAC; September 14–17, 2003; Chicago, IL. Abstract M-1759.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (30970131) and the Key Project of Chinese Ministry of Education (107002) to Wei Liu.

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Authors and Affiliations

  1. Department of Dermatology, Peking University First Hospital, Research Center for Medical Mycology, Peking University, No. 8, Xishiku St., 100034, Beijing, People’s Republic of China

    Yi Sun, Wei Liu, Zhe Wan, Xiaohong Wang & Ruoyu Li

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  1. Yi Sun
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Correspondence to Wei Liu.

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Sun, Y., Liu, W., Wan, Z. et al. Antifungal Activity of Antifungal Drugs, as Well as Drug Combinations Against Exophiala dermatitidis . Mycopathologia 171, 111–117 (2011). https://doi.org/10.1007/s11046-010-9358-6

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  • DOI: https://doi.org/10.1007/s11046-010-9358-6

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