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In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis

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Abstract

Otomycosis is a common mycotic infection of the external auditory canal, and Aspergillus species are one of the most frequent causative agents worldwide. The limited antifungal arsenal, the high toxicity and side effects of antifungal agents, and the growing resistance to the currently available antifungals underscore the need for new therapeutic strategies. The present study aimed to evaluate the combined in vitro efficacy of terbinafine and ketoconazole against Aspergillus species with terbinafine high MIC values isolated from patients with otomycosis.

84 Aspergillus species with high MIC values to terbinafine (≥ 4 µg/ml), consisting of A. flavus, A. tubingensis, A. niger, and A. terreus, were included in this study. The checkerboard microdilution method evaluated the in vitro interactions using the CLSI reference technique. Synergistic effects were observed for 66.67% (56/84) of all isolates (FICI ranging from 0.19 to 0.5). However, the interactions of terbinafine and ketoconazole exhibited indifference in 33.33% (28/84) of the isolates, and no antagonism was observed for any combination. The interaction of terbinafine and ketoconazole showed synergistic activity against Aspergillus species with high MIC values, suggesting that this is an alternative and promising approach for treating otomycosis.

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Data Availability

All data generated or analyzed during this study are included in this published article. The data used or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This dissertation has been done with the financial support of Mazandaran University of Medical Sciences (grant no: 8937), which we gratefully acknowledge.

Funding

This work was supported by Invasive Fungi Research Center, Mazandaran University of Medical Sciences Deputy of Research 8937, Sari, Iran

Author information

Authors and Affiliations

  1. Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran Province, Iran

    Mohsen Nosratabadi, Mohammad Taghi Hedayati, Tahereh Shokohi, Hamid Badali, Maryam Moazeni, Seyed Reza Aghili, Javad Javidnia, Leila Faeli, Shaghayegh Khojasteh, Behrad Roohi, Mahdi Abastabar & Iman Haghani

  2. Student Research Committee, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Amirreza Espahbodi & Javad Javidnia

  3. Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

    Mohammad Taghi Hedayati, Tahereh Shokohi, Hamid Badali, Maryam Moazeni, Seyed Reza Aghili, Mahdi Abastabar & Iman Haghani

  4. Department of Molecular Microbiology & Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, TX, USA

    Hamid Badali

  5. Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

    Majid Saeedi

  6. Department of Microbiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran

    Kiana Abbasi

Authors
  1. Mohsen Nosratabadi
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Contributions

MN, AE, LF, BR, KA, and ShKh Collected the data, IH and MA interpreted data and drafted and revised the manuscript for important intellectual content. MH, TSh, HB, MS, MM, and SRA reviewed the analyses and the final version of the manuscript. JJ performed the statistical analysis IH, and MA interpreted the data and approved the final version. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Mahdi Abastabar or Iman Haghani.

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All authors declare that there is no conflict of interest.

Ethical Approval

The Ethics Committee approved this research of the Mazandaran University of Medical Sciences (IR.MAZUMS.REC.1400.284).

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Handling Editor: Abdullah Mohammed Said Al-Hatmi.

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Nosratabadi, M., Espahbodi, A., Hedayati, M.T. et al. In Vitro Combination of Terbinafine with Ketoconazole Against Aspergillus Species with Terbinafine High MIC Values Isolated From Otomycosis. Mycopathologia 188, 119–127 (2023). https://doi.org/10.1007/s11046-022-00698-7

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