Antifungal susceptibility profiles of otomycosis etiological agents in Ahvaz, Iran

Document Type : Original Articles

Authors

1 Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Otorhinolaryngologist, Apadana Hospital, Sorosh Street, Ahvaz, Iran

Abstract

Background and Purpose: Otomycosis is a secondary ear fungal infection among predisposed individuals in humid conditions. Aspergillus species are the most common etiologic agents of this infection. Several ototopical antifungals are currently used for the treatment of this disease; however, recurrence and treatment failure are usually observed in some cases. Regarding this, the present study was conducted to investigate the antifungal activity of caspofungin, azoles, and terbinafine against the isolated agents of otomycosis.
Materials and Methods: This study was conducted on the specimens collected from 90 patients with otomycosis. The samples were cultured on Sabouraud dextrose agar and identified based on morphological characteristics, physiological tests, and microscopic features. Furthermore, the microdilution method was used for antifungal susceptibility testing according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Finally, the minimum inhibitory concentration (MIC) and minimum effective concentration (MEC) ranges, MIC/MEC50, MIC/MEC90, and geometric mean (GM) MIC/MEC were calculated for the isolates.
Results: According to the results, 77 patients with otomycosis were positive for different Aspergillus (88.3%) and Candida (11.7%) species. Aspergillus niger complex (n=36) was found to be the most common agent, followed by A. flavus, A. terreus, and A. nidulans complexes. Furthermore, epidemiological cutoff values (ECVs) were lower than those presented by the CLSI for itraconazole and caspofungin in 98.5% and 42.6% of Aspergillus species, respectively. Terbinafine exhibited a great activity against Aspergillus species, while fluconazole revealed a low activity against both Aspergillus species. Based on the results, 77.8% of Candida species were resistant to caspofungin; however, miconazole and econazole had low MIC ranges.
Conclusion: Aspergillus niger and A. flavus complexes were identified as the most common agents accounting for 85.7% of the isolates. In addition, terbinafine was identified as the best antifungal for both Aspergillus and Candida species. Moreover, tested azoles had relatively low MICs, whereas most of the isolates had the MIC values beyond the caspofungin ECVs.

Keywords


1. Kiakojuri K, Rajabnia R, Jalili B, Khafri S, Omran SM. Otomycosis in adolescent patients referred to the therapeutic centers in Babol city, Iran. Jundishapur J Microbiol. 2015;
8(5):e17138.
2. Zarei Mahmoudabadi A, Abshirini H, Rahimi R. Fungal flora of hearing aid moulds and ear canal in hearing aid wearers in school children in Ahvaz, Iran (2008). Jundishapur J Microbiol. 2009; 2(1):22-4.
3. Gharaghani M, Seifi Z, Zarei Mahmoudabadi A. Otomycosis in Iran: a review. Mycopathologia. 2015; 179(5-6):415-24.
4. Kazemi A, Majidinia M, Jaafari A, Ayatollahi Mousavi SA, Zarei Mahmoudabadi A, Alikhah H. Etiologic agents of otomycosis in the north-western area of Iran. Jundishapur J Microbiol. 2015; 8(9):e21776.
5. Viswanatha B, Naseeruddin K. Fungal infections of the ear in immunocompromised host: a review. Mediterr J Hematol Infect Dis. 2011; 3(1):e2011003.
6. Szigeti G, Sedaghati E, Mahmoudabadi AZ, Naseri A, Kocsube S, Vagvolgyi C, et al. Species assignment and antifungal susceptibilities of black aspergilli recovered from otomycosis cases in Iran. Mycoses. 2012; 55(4):333-8.
7. Abastabar M, Haghani I, Ahangarkani F, Rezai MS, Taghizadeh Armaki M, Roodgari S, et al. Candida auris otomycosis in Iran and review of recent literature. Mycoses. 2019; 62(2):101-5.
8. Barati B, Okhovvat SA, Goljanian A, Omrani MR. Otomycosis in central Iran: a clinical and mycological study. Iran Red Crescent Med J. 2011; 13(12):873-6.
9. Ho T, Vrabec JT, Yoo D, Coker NJ. Otomycosis: clinical features and treatment implications. Otolaryngol head Neck Surg. 2006; 135(5):787-91.
10. Vennewald I, Klemm E. Otomycosis: diagnosis and treatment. Clin Dermatol. 2010; 28(2):202-11.
11. Khan F, Muhammad R, Khan MR, Rehman F, Iqbal J, Khan M, et al. Efficacy of topical clotrimazole in treatment of otomycosis. J Ayub Med College, Abbottabad. 2013; 25(1-2):78-80.
12. Ologe F, Nwabuisi C. Treatment outcome of otomycosis in Ilorin, Nigeria. West Afr J Med. 2001; 21(1):34-6.
13. Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004; 39(11):1563-71.
14. Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, et al. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002; 347(25):2020-9.
15. Badali H, Fakhim H, Zarei F, Nabili M, Vaezi A, Poorzad N, et al. In vitro activities of five antifungal drugs against opportunistic agents of Aspergillus Nigri complex. Mycopathologia. 2016; 181(3-4):235-40.
16. Kahn JN, Hsu MJ, Racine F, Giacobbe R, Motyl M. Caspofungin susceptibility in Aspergillus and non-Aspergillus molds: inhibition of glucan synthase and reduction of β-d-1, 3 glucan levels in culture. Antimicrob Agents Chemother. 2006; 50(6):2214-6.
17. Diekema DJ, Messer SA, Hollis RJ, Jones RN, Pfaller MA. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J Clin Microbiol. 2003; 41(8):3623-6.
18. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi; CLSI document M38-3rd. 3rd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.
19. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; CLSI standard M27. 4th ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.
20. Espinel-Ingroff A, Diekema DJ, Fothergill A, Johnson E, Pelaez T, Pfaller MA, et al. Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). J Clin Microbiol. 2010; 48(9):3251-7.
21. Clinical and Laboratory Standards Institute. Epidemiological cutoff values for antifungal susceptibility testing; CLSI supplement M59. 2nd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
22. Clinical and Laboratory Standards Institute. Reference method for broth dilution antifungal susceptibility testing of yeasts; fourth informational supplement. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
23. Munguia R, Daniel SJ. Ototopical antifungals and otomycosis: a review. Int J Pediatr Otorhinolaryngol. 2008; 72(4):453-9.
24. Chappe M, Vrignaud S, de Gentile L, Legrand G, Lagarce F, Le Govic Y. Successful treatment of a recurrent Aspergillus niger otomycosis with local application of voriconazole. J Mycol Med. 2018; 28(2):396-8.
25. Jia X, Liang Q, Chi F, Cao W. Otomycosis in Shanghai: aetiology, clinical features and therapy. Mycoses. 2012; 55(5):404-9.
26. Nemati S, Hassanzadeh R, Khajeh Jahromi S, Delkhosh Nasrollah Abadi A. Otomycosis in the north of Iran: common pathogens and resistance to antifungal agents. Eur Arch Otorhinolaryngol. 2014; 271(5):953-7.
27. Saunders JE, Raju RP, Boone JL, Hales NW, Berryhill WE. Antibiotic resistance and otomycosis in the draining ear: culture results by diagnosis. Am J Otolaryngol. 2011; 32(6):470-6.
28. Karaarslan A, Arikan S, Ozcan M, Ozcan KM. In vitro activity of terbinafine and itraconazole against Aspergillus species isolated from otomycosis. Mycoses. 2004; 47(7):284-7.
29. Alcazar-Fuoli L, Mellado E, Alastruey-Izquierdo A, Cuenca-Estrella M, Rodriguez-Tudela JL. Species identification and antifungal susceptibility patterns of species belonging to Aspergillus section Nigri. Antimicrob Agents Chemother. 2009; 53(10):4514-7.
30. Zarei Mahmoudabadi A, Seifi Z, Gharaghani M. Lamisil, a potent alternative antifungal drug for otomycosis. Curr Med Mycol. 2015; 1(1):18-21.
31. Pfaller M, Boyken L, Hollis R, Kroeger J, Messer S, Tendolkar S, et al. In vitro susceptibility of clinical isolates of Aspergillus spp. to anidulafungin, caspofungin, and micafungin: a head-to-head comparison using the CLSI M38-A2 broth microdilution method. J Clin Microbiol. 2009; 47(10):3323-5.
32. Arikan S, Lozano-Chiu M, Paetznick V, Rex JH. In vitro susceptibility testing methods for caspofungin against aspergillus and fusarium isolates. Antimicrob Agents Chemother. 2001; 45(1):327-30.
33. Yenisehirli G, Bulut Y, Guven M, Gunday E. In vitro activities of fluconazole, itraconazole and voriconazole against otomycotic fungal pathogens. J Laryngol Otol. 2009; 123(9):978-81.
34. Ahmed MR, Abou-Halawa AS, Hessam WF, Abdelkader DS. A search for new otomycotic species and their sensitivity to different antifungals. Interv Med Appl Sci. 2018; 10(3):145-9.
35. Pfaller M, Boyken L, Hollis R, Messer S, Tendolkar S, Diekema D. In vitro susceptibilities of Candida spp. to caspofungin: four years of global surveillance. J Clin Microbiol. 2006; 44(3):760-3.