Abstract

  Cases of onychomycosis caused by non-dermatophyte filamentous fungi have increased over the years. It is worth noting that this group of fungi is resistant to fluconazole, thus the importance of determining the in vitro susceptibility patterns to the antifungals available. We determined the minimal inhibitory concentration of amorolfine, ciclopirox, itraconazole and terbinafine using the microdilution method M38-A, as described by the Clinical Laboratory and Standards Institute, of 13 isolates of Aspergillus versicolor obtained from onychomycosis. The final concentrations were: 0.13-64 μg/mL for amorolfine and terbinafine, 0.06 - 32 μg/mL for ciclopirox and 0.03-16 μg/mL for itraconazole. Also, we determined the interaction of these drugs by the checkerboard method. The MIC₅₀ and MIC₉₀ were ≥ 64.00 and ≥ 64.00 µg/mL for amorolfine, 4.00 and 8.00 µg/mL for ciclopirox, 1.00 and 1.80 µg/mL for itraconazole and 0.50 and 1.36 µg/mL for terbinafine, respectively. Regarding the combination of antifungals, 15.38% of the combinations of ciclopirox-itraconazole presented synergism, while the rest of the combinations showed no interaction. Thus, in vitro susceptibility testing indicates that terbinafine exhibited the highest antifungal activity and amorolfine the lowest against A. versicolor. Also, combining treatments enhances the activity of the drugs, proving a possible alternative for successful treatment of onychomycosis caused by this fungus.

Keywords: Aspergillus versicolor Amorolfine; Ciclopirox; Itraconazole; Terbinafine

References

1. Pérez JE. “La onicomicosis: de sus implicaciones cosméticas a las dificultades en su tratamiento”. Biosalud 10.1 (2011): 5-6.
2. Salas-Campos I., et al. “Agentes etiológicos de onicomicosis diagnosticadas en el laboratorio de micología médica de la Universidad de Costa Rica”. Acta Médica Costarricense 54.2 (2012): 114-118.
3. Asbati M., et al. “Onicomicosis por hongos no dermatofitos: Estudio retrospectivo en 4 años”. Revista de la Sociedad Venezolana de Microbiología 22.2 (2002): 147-152.
4. Mügge C., et al. “Causative agents of onychomycosis – a retrospective study”. Journal der Deutschen Dermatologischen Gesellschaft 4.3 (2006): 218-227.
5. Salas-Campos I., et al. “Onicomicosis por hongos fuliginosos”. Acta Médica Costarricense 51.4 (2009): 241-244.
6. Gross-Martínez NT., et al. “Métodos diagnósticos en micología médica”. 1st ed. San José: Editorial UCR (2012).
7. Llambrich A., et al. “Tratamiento actual de las onicomicosis”. Revista Iberoamericana de Micología 19 (2002): 127-129.
8. Escobar M., et al. “Onicomicosis por hongos ambientales no dermatofitos”. Revista Iberoamericana de Micología 20 (2003): 6-10.
9. Carrillo-Muñoz A., et al. “Antifúngicos para el tratamiento de las micosis ungueales”. Revista Iberoamericana de Micología 27 (2010): 49-56.
10. Torres-Rodríguez JM., et al. “Aspergillus versicolor as cause of onychomycosis: report of 12 cases and susceptibility testing to antifungal drugs”. Journal of the European Academy of Dermatology and Venereology 11.1 (1998): 25-31.
11. Barrantes-Ortiz N., et al. “Susceptibilidad in vitro a antifúngicos de aislamientos de Scopulariopsis sp. provenientes de onicomicosis”. Dermatología Revista México 63.3 (2019): 261-267.
12. Sequeira-Oviedo PM., et al. “Susceptibilidad antimicrobiana de los aislamientos de Fusarium solani provenientes de onicomicosis”. Dermatología Revista México 61.3 (2017): 197-205.
13. Carrillo-Muñoz A., et al. “In vitro activity of voriconazole against dermatophytes, Scopulariopsis brevicaulis and other opportunistic fungi as agents of onychomycosis”. International Journal of Antimicrobial Agents 30.2 (2007): 157-161.
14. Cantón R., et al. “Capítulo 15 Métodos estandarizados por el CLSI para el estudio de la sensibilidad a los antifúngicos (documentos M27-A3, M38-A y M44-A)”. En: Pemán J, Martín-Mazuelos E, Rubio-Calvo MC, editores. Guía Práctica de Identificación y Diagnóstico en Micología Clínica. Bilbao, 2007: ISBN: 978-84-611-8776-8.
15. Dorsthorst D., et al. “Comparison of fractional inhibitory concentration index with response surface modeling for characterization of in vitro interaction of antifungals against itraconazole susceptible and resistant Aspergillus fumigatus”. Antimicrobial Agents and Chemotherapy 46.3 (2002): 702-707.
16. Semis R., et al. “Evaluation of antifungal combinations of nystatin-intralipid against Aspergillus terreus using checkerboard and disk diffusion methods”. Journal de Mycologie Médicale 25.1 (2015): 63-70.
17. Díaz- Jarabrán MC., et al. “Evaluación del perfil de sensibilidad in vitro de aislamientos clínicos de Trichophyton mentagrophytes y Trichophyton rubrum aislados en Chile”. Revista Iberoamericana de Micología 32.2 (2015): 83-87.
18. Chavez J., et al. “Sensibilidad in vitro de hongos miceliales de aislamientos clínicos en pacientes con cáncer en el Instituto Nacional de Cancerología ESE”. Infectio 14.2 (2010): 116-126.
19. García-Martos P., et al. “Actividad in vitro de anfotericina B, itraconazol y voriconazol frente a 20 especies de Aspergillus empleando el método de microdilución Sensititre®”. Enfermedades Infecciosas y Microbiología Clínica 23.1 (2005): 15-26.
20. Snelders E., et al. “Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism”. PloS Medicine 5.11 (2008): e219.
21. Rodríguez-Tudela JL., et al. “Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus”. Antimicrobial Agents and Chemotherapy 52.7 (2008): 2468-2472.
22. Mortensen K., et al. “Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark and Spain”. Antimicrobial Agents and Chemotherapy 54.11 (2010): 4545-4549.
23. Mellado E., et al. “Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species”. Journal of Clinical Microbiology 39.7 (2001): 2431-2438.
24. Neelabh, “ABC and MFS transporters: a reason for antifungal drug resistance”. Archives of Biotechnology and Biomedicine 2 (2018) 001-007.
25. Meneau I., et al. “Identification of Aspergillus fumigatus multigrug transporters genes and their potential involvent in antifungal resistance”. Medical Mycology 54.6 (2016): 616-627.
26. Sonthalia S., et al. “Topical ciclopirox olamine 1 %: Revisiting a unique antifungal”. Indian Dermatology Online Journal 10.4 (2019): 481-485.
27. Liu X., et al. “Primary cutaneous aspergillosis caused by Aspergillus fumigatus in an immunocompetent patient”. Medicine 96.48 (2017): e8916.
28. Li R., et al. “In vitro susceptibility testing of amorolfine in pathogenic fungi isolated from dermatomycosis patients in China”. Mycoses 47 (2004): 402-406.
29. Gupta AK., et al. “In vitro susceptibility testing of ciclopirox, terbinafine, ketoconazole and itraconazole against dermatophytes and nondermatophytes, and In vitro evaluation of combination antifungal activity”. British Journal of Dermatology 149.2 (2003): 296-305.
30. Chaturvedi V., et al. “Multilaboratory testing of two-drug combinations of antifungals against Candida albicans, Candida glabrata and Candida parapsilosis”. Antimicrobial Agents and Chemotherapy 55.4 (2011): 1543-1548.

Citation

Citation: Daniela Jaikel-Víquez., et al. In vitro Activity of Amorolfine, Ciclopirox, Itraconazole and Terbinafine Against Aspergillus versicolor as Agent of Onychomycosis Acta Scientific Microbiology 3.3 (2020): 01-06.

Copyright

Copyright: © 2020 SDaniela Jaikel-Víquez., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.