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Susceptibility and resistance of Sporothrix brasiliensis to branded and compounded itraconazole formulations

  • Veterinary Microbiology - Short Communication
  • Published:
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Abstract

Itraconazole is the first drug of choice for the treatment of sporotrichosis and it is available at different concentrations for veterinary patients. However, therapeutic failure has been reported, limiting clinical treatment. This study evaluated the in vitro efficacy of brand-name and compounded itraconazole formulations against Sporothrix brasiliensis and estimated the itraconazole content in each tested formulation. Oral capsules were acquired from two brand-name products for human (H-IND) and veterinary (V-IND) uses, and three from compounding pharmacies in Pelotas, RS, for human (H-COMP1/H-COMP2) and veterinary (V-COMP) uses. Capsule purity was analyzed by liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). Antifungal activity was determined against 29 Sporothrix brasiliensis by the M38-A2 guideline of CLSI. H-IND/H-COMP1/H-COMP2 had high efficacy against S. brasiliensis (approximately 70% of total isolated susceptible), V-COMP showed moderate efficacy (51.7%), and V-IND was the least effective formulation (37.9%). Thirty-four percent of the total isolates were resistant to all formulations. Furthermore, itraconazole content did not match the concentration indicated by the manufacturers, ranging from 387.70 to 7.81 μg/mg (H-COMP2 > V-COMP > H-IND > H-COMP1 > V-IND). Therefore, it is possible that the formulations showed different in vitro efficacy due to the difference in their itraconazole contents. Given the emergence of antifungal resistance for all formulations, the choice product to be used must follow susceptibility testing. Stringent quality control measures are recommended for product manufactures to assure drug content uniformity.

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Acknowledgments

We thank Dr. Zoilo Pires de Camargo (Universidade Federal de São Paulo, Brazil) for the biomolecular analysis; and Dr. João Luiz Zani (Universidade Federal de Pelotas, Brazil) for providing one of the itraconazole used in this study. The authors are grateful for the scholarships provided by CAPES, FAPERGS, and CNPq.

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Authors and Affiliations

  1. Departamento de Clínicas Veterinária, Faculdade de Veterinária, Universidade Federal de Pelotas, Campus Universitário Capão do Leão, n° 1, Pelotas, Rio Grande do Sul, Brazil

    Stefanie Bressan Waller & Marlete Brum Cleff

  2. Departamento de Veterinária Preventiva, Faculdade de Veterinária, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, Brazil

    Stefanie Bressan Waller, Márcia Kutscher Ripoll, Renata Osório de Faria & Mário Carlos Araújo Meireles

  3. Centro de Controle de Zoonoses, Pelotas, Rio Grande do Sul, Brazil

    Isabel Martins Madrid

  4. Departamento de Ciência e Tecnologia Agroindustrial, Faculdade de Agronomia, Programa de Pós-Graduação em Ciência e Tecnologia de Alimentos, Pelotas, Rio Grande do Sul, Brazil

    Tanize Acunha & Fábio Clasen Chaves

  5. Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    João Roberto Braga de Mello

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  1. Stefanie Bressan Waller
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Correspondence to Stefanie Bressan Waller.

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Waller, S.B., Ripoll, M.K., Madrid, I.M. et al. Susceptibility and resistance of Sporothrix brasiliensis to branded and compounded itraconazole formulations. Braz J Microbiol 52, 155–162 (2021). https://doi.org/10.1007/s42770-020-00280-7

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