Detection of fungal infections, drug resistance, and the impact of terbinafine hydrochloride cream treatment on fungal clearance rate in patients with fungal otitis externa

doi:10.5246/jcps.2026.04.026

Abstract

Abstract:

This study aimed to evaluate fungal detection, antifungal drug resistance, and the therapeutic efficacy of terbinafine hydrochloride cream (THC) in promoting fungal clearance in patients with fungal otitis externa. A retrospective analysis was conducted on 126 patients treated between January 2020 and October 2023. Patients were assigned to a control group, receiving 3% salicylic acid alcohol solution, or a study group, receiving a combination of the solution and THC. Outcomes assessed included fungal clearance, clinical symptom improvement, drug resistance, adverse reactions, and recurrence rates. The results demonstrated that the study group achieved a significantly higher fungal clearance rate (82.54%) compared to the control group (61.90%). Additionally, patients in the study group showed more rapid symptom resolution and a markedly lower recurrence rate (3.33% vs. 22.95%). These findings indicated that the combination of THC and salicylic acid alcohol solution was an effective and well-tolerated treatment for fungal otitis externa.

Key words: Fungal otitis externa, Drug resistance, Terbinafine hydrochloride cream, Fungal clearance rate, Antifungal drugs, Clinical symptoms, Recurrence

Supporting:

Youwei Wu, Ying Lu, Changming Wu, Feng Zhang. Detection of fungal infections, drug resistance, and the impact of terbinafine hydrochloride cream treatment on fungal clearance rate in patients with fungal otitis externa[J]. Journal of Chinese Pharmaceutical Sciences, 2026, 35(4): 372-380.

Figures/Tables 5

Table 1. Clinical features.

Table 2. Fungal distribution (n (%)).

Table 3. Analysis of drug resistance in fungi (n (%)).

Table 4. Clinical symptoms (n (%)).

Table 5. Adverse reactions during treatment (n (%)).

References 28

[1]	Ito, Y.; Inoue, N.; Kaneko, N.; Otsuka, M.; Yamasaki, S.; Yoshikawa, M. A case of fungal otitis externa caused by coinfection of Candida auris and Aspergillus flavus. J. Infect. Chemother. 2023, 29, 809–811.
[2]	Khribi, M.; El Abed, W.; Gnaba, K. Malignant otitis externa: a persistent challenge. La Tunis. Médicale. 2024, 102, 478–482.
[3]	Mostafa, M.G.; Ahmed, S.; Islam, M.R.; Rahman, M.A.; Khan, L.; Alam, M.M.; Ahmed, M.B. Efficacy of clotrimazole 1% solution compared to econazole nitrate 1% + triamcinolone acetonide 0.1% cream in patients with otomycosis. Mymensingh Med. J. 2021, 30, 638–643.
[4]	Jimenez-Garcia, L.; Celis-Aguilar, E.; Díaz-Pavón, G.; Muñoz Estrada, V.; Castro-Urquizo, Á.; Hernández-Castillo, N.; Amaro-Flores, E. Efficacy of topical clotrimazole vs. topical tolnaftate in the treatment of otomycosis. A randomized controlled clinical trial. Braz. J. Otorhinolaryngol. 2020, 86, 300–307.
[5]	Tang, W.; Wang, C. Bis-boric acid-mediated regioselective reductive aminolysis of 3,4-epoxy alcohols. J. Org. Chem. 2022, 87, 15653–15660.
[6]	Yassin, Z.; Amirzargar, B.; Ghasemi, R.; Valizadeh, F.; Fattahi, M. Comparison of acidifying agents and clotrimazole for treatment of otomycosis: a comprehensive one-way mini-review. Curr. Med. Mycol. 2023, 9, 45–51.
[7]	Nemati, S.; Gerami, H.; Faghih Habibi, A.; Kazemnejad, E.; Shabani, N.; Aghsaghloo, V.; Montazeri, S. Sertaconazole versus clotrimazole and miconazole creams in the treatment of otomycosis: a placebo-controlled clinical trial. Iran J. Otorhinolaryngol. 2022, 34, 27–34.
[8]	Xu, S.; Li, J.F.; Ding, L.; Gao, K.; Xie, F.Y.; Han, J.; Zhou, X.C. Efficacy and safety of terbinafine hydrochloride spray and 3% boric acid alcohol ear drops in otomycosis. Acta Oto Laryngol. 2020, 140, 302–306.
[9]	Peng, Y.X. Diagnosis and treatment of otitis externa mycotica: experiences with 216 cases. Chin. J. Otol. 2019, 17, 522–526.
[10]	Kong, W.X.; Zhou, L. Otorhinolaryngology-Head and Neck Surgery, 3rd ed.; People’s Medical Publishing House: Beijing. 2025, 116–117.
[11]	Medical Administration Department, Ministry of Health, PRC. National Guide to Clinical Laboratory Procedures, 3rd ed.; Southeast University Press: Nanjing. 2006, 126–137.
[12]	CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Clinical and Laboratory Standards Institute: Wayne, PA, 2017.
[13]	Sogebi, O.A.; Oyewole, E.A.; Osinupebi, O.A. Clinicopathological study of otomycosis in a tertiary hospital in South-west Nigeria. Afr Health Sci. 2024, 24, 69–75.
[14]	Hasnaoui, M.; Ben Mabrouk, A.; Chelli, J.; Larbi Ammari, F.; Lahmar, R.; Toumi, A.; Mighri, K. Necrotising otitis externa: a single centre experience. J. Otol. 2021, 16, 22–26.
[15]	Noroy, L.; Pujo, K.; Leghzali-Moise, H.; Saison, J. Aspergillus necrotizing otitis externa with temporomandibulozygomatic involvement. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2020, 137, 127–129.
[16]	Cheema, K.; Awan, N.; Raza, N.; Khan, K.; Qamar, S.; Ashraf, S. Association of Comorbid Conditions with Six-Month Survival and Disease Outcome in Patients of Necroinflammatory Otitis Externa. J. Coll. Physicians Surg. Pak. 2020, 30, 498–502.
[17]	Hao, X.K.; Zhou, J.; Li, N. Distribution and Drug Resistance of Fungal Pathogens in Patients with Otomycosis. Chin. Rem. Clin. 2022, 22, 21–23.
[18]	McCarty Walsh, E.; Hanson, M.B. Fungal infections of the external auditory canal and emerging pathogens. Otolaryngol. Clin. North Am. 2023, 56, 909–918.
[19]	Roohi, B.; Nemati, S.; Alipour, A.; Faeli, L.; Mayahi, S.; Haghani, I.; Shalchizadeh, M.; Darini, A.; Al-Hatmi, A.M.S.; Abastabar, M.; Shokohi, T. Otomycosis: The foremost aetiological agent causing otitis externa and the antifungal susceptibility pattern in North-Western Iran. Mycoses. 2023, 66, 87–97.
[20]	Jing, R.; Yang, W.H.; Xiao, M.; Li, Y.; Zou, G.L.; Wang, C.Y.; Li, X.W.; Xu, Y.C.; Hsueh, P.R. Species identification and antifungal susceptibility testing of Aspergillus strains isolated from patients with otomycosis in northern China. J. Microbiol. Immunol. Infect. 2022, 55, 282–290.
[21]	Gharaghani, M.; Halvaeezadeh, M.; Ali Jalaee, G.; Taghipour, S.; Kiasat, N.; Zarei Mahmoudabadi, A. Antifungal susceptibility profiles of otomycosis etiological agents in Ahvaz, Iran. Curr. Med. Mycol. 2020, 6, 18–22.
[22]	Kaminer, B.M.; El-Saied, S.; Lasry, B.; Kaplan, D.M. Diagnostic accuracy of eosinophil-to-lymphocyte ratio and eosinophil-to-neutrophil ratio as biomarkers for differentiating between fungal and bacterial infection in necrotising otitis externa. Clin. Otolaryngol. 2024, 49, 343–348.
[23]	Lee, J.S.; Lee, S.M.; Son, H.S.; Yoon, Y.N.; Shin, J.E.; Sul, W.J.; Yu, D.A.; Choe, Y.B.; Lee, Y.W. Analysis of the microbiome of the ear canal in normal individuals and patients with chronic otitis externa. Ann. Dermatol. 2022, 34, 461.
[24]	Du, Y.C.; Liu, H.H. Effect of terbinafine hydrochloride cream combined with 3% boric acid alcohol ear drops on fungal otitis externa. Chin. J. Mycol. 2022, 17, 227–230.
[25]	Peled, C.; Novoa, R.; El-Saied, S.; Sadeh, R.; Novack, V.; Kaplan, D.M. Computer tomography findings in necrotizing otitis externa based on the offending pathogens. Eur. Arch. Oto Rhino Laryngol. 2021, 278, 4707–4713.
[26]	Shang, L.M.; Liu, F.X.; Zhong, Y.Y.; Yu, J.F. Clinical curative effect of sodium bicarbonate for ear bath combined with triamcinolone econazole cream on fungal otitis externa and its influences on negative conversion ratio of fungi. Chin. J. Otorhinolaryngol. Integr. Med. 2021, 29, 422–424.
[27]	Kiakojuri, K.; Mahdavi Omran, S.; Roodgari, S.; Taghizadeh Armaki, M.; Hedayati, M.T.; Shokohi, T.; Haghani, I.; Javidnia, J.; Kermani, F.; Badali, H.; Abastabar, M. Molecular identification and antifungal susceptibility of yeasts and molds isolated from patients with otomycosis. Mycopathologia. 2021, 186, 245–257.
[28]	Sun, J.; Dai, W.B.; Liang, Z.; Wang, Z.Y.; Huang, C.S.; He, B.; Zhang, H.; Wang, X.Q.; Zhang, Q. Advances in the formulation and delivery technology of paclitaxel for injection. J. Chin. Pharm. Sci. 2015, 24, 487–500.