Evaluation of the antifungal activity of ketoconazole against strains of Microsporum sp. and development of a pharmaceutical cream formulation

Authors

Keywords:

ketoconazole cream, topical antifungal formulation, dermatophyte infections, microbial, Microsporum sp.

Abstract

Introduction: In Ecuador, the prevalence of dermatophytes is influenced by various factors such as environmental conditions, sociocultural practices, occupational exposures, hygiene routines and individual immune status; however, despite the significant burden of fungal diseases, there is a lack of data in Ecuador, which hinders the development of effective control and monitoring strategies.

Objective: To evaluate the antifungal activity of ketoconazole against M. canis strains and develop a pharmaceutical cream formulation to treat infections caused by this dermatophyte.

Results: Both formulations exhibited satisfactory physical stability. However, only formulation A containing EDTA demonstrated effective inhibition of microbial growth, as evidenced by the absence of pink discoloration and bubble formation. In contrast, formulation B showed signs of microbial contamination, probably due to an inadequate preservative content. Additionally, clinical studies demonstrated the effectiveness of ketoconazole 2% cream in the treatment of various dermatophyte infections, comparable to clotrimazole cream.

Conclusions: MIC results varied between studies and even between strains of the same species. Using the MIC breakpoints for Candida albicans, the obtained result of 4 μg/mL indicates that M. canis shows intermediate sensitivity to the drug.

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References

1. de Pauw BE. What are fungal infections?. Mediterr J Hematol Infect Dis [Internet]. 2011 [Citado 02/06/2023];3(1):e2011001. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/21625304

2. Rodrigues ML, Nosanchuk JD. Fungal diseases as neglected pathogens: A wake-up call to public health officials. PLoS Negl Trop Dis [Internet]. 2020 Feb [Citado 02/06/2023];14(2):e0007964. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/32078635

3. Pasquetti M, Min ARM, Scacchetti S, Dogliero A, Peano A. Infection by Microsporum canis in Paediatric Patients: A Veterinary Perspective. Vet Sci [Internet]. 2017 Sep 19 [Citado 02/06/2023];4(3). Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/29056704

4. Cabañes FJ. Ringworm in cats and dogs: New guidelines. Rev Iberoam Micol [Internet]. 2021 Jan [Citado 02/06/2023];38(1):1–2. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1130140620300206

5. A.Makawi Z, Yasin Jassim S. Prevalence and Risk Factors for Giardia Species in Livestock Animals of Iraq. Bionatura [Internet]. 2023 Sep 15 [Citado 02/06/2023];8(3):1–6. Disponible en: https://www.revistabionatura.com/2023.08.03.95.html

6. Segal E, Elad D. Human and Zoonotic Dermatophytoses: Epidemiological Aspects. Front Microbiol [Internet]. 2021 Aug 6 [Citado 02/06/2023];12. Disponible en: https://www.frontiersin.org/articles/10.3389/fmicb.2021.713532/full

7. Martinez-Rossi NM, Peres NTA, Bitencourt TA, Martins MP, Rossi A. State-of-the-Art Dermatophyte Infections: Epidemiology Aspects, Pathophysiology, and Resistance Mechanisms. J fungi (Basel, Switzerland) [Internet]. 2021 Aug 3 [Citado 02/06/2023];7(8). Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/34436168

8. Saied Hamied A. Submission and Phylogenetical of Local Isolated Trichophyton interdigitale of Iraqi Patients in NCBI. Bionatura [Internet]. 2022 Sep 15 [Citado 02/06/2023];7(3):1–5. Disponible en: https://www.revistabionatura.com/2022.07.03.25.html

9. Greywal T, Friedlander SF. Dermatophytes and Other Superficial Fungi. En su: Principles and Practice of Pediatric Infectious Diseases [Internet]. Philadelphia: Elsevier; 2018. pp. 1282-1287.e2 [Citado 02/06/2023]. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/B9780323401814002541

10. Khoza S, Moyo I, Ncube D. Comparative Hepatotoxicity of Fluconazole, Ketoconazole, Itraconazole, Terbinafine, and Griseofulvin in Rats. J Toxicol [Internet]. 2017 [Citado 02/06/2023];2017:1–9. Disponible en: https://www.hindawi.com/journals/jt/2017/6746989/

11. Sinawe H, Casadesus D. Ketoconazole [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [Citado 02/06/2023]. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/31643176

12. Ghannoum MA, Rice LB. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev [Internet]. 1999 Oct [Citado 02/06/2023];12(4):501–17. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/10515900

13. Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res [Internet]. 2010 Dec 20 [Citado 02/06/2023];4:11–24. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/21386951

14. Rahman MT, Sobur MA, Islam MS, Ievy S, Hossain MJ, El Zowalaty ME, et al. Zoonotic Diseases: Etiology, Impact, and Control. Microorganisms [Internet]. 2020 Sep 12 [Citado 02/06/2023];8(9):1405. Disponible en: https://www.mdpi.com/2076-2607/8/9/1405

15. Albán Jácome GE, Fernández Andreu CM, Illnait Zaragozí MT. Dermatofitosis en Ecuador. INSPILIP [Internet]. 2021 May 26 [Citado 02/06/2023];5(1). Disponible en: https://www.inspilip.gob.ec/index.php/inspi/article/view/9

16. Kruithoff C, Gamal A, McCormick TS, Ghannoum MA. Dermatophyte Infections Worldwide: Increase in Incidence and Associated Antifungal Resistance. Life [Internet]. 2023 Dec 19 [Citado 02/06/2023];14(1):1. Disponible en: https://www.mdpi.com/2075-1729/14/1/1

17. Keshwania P, Kaur N, Chauhan J, Sharma G, Afzal O, Alfawaz Altamimi AS, et al. Superficial Dermatophytosis across the World’s Populations: Potential Benefits from Nanocarrier-Based Therapies and Rising Challenges. ACS Omega [Internet]. 2023 Sep 5 [Citado 02/06/2023];8(35):31575–99. Disponible en: https://pubs.acs.org/doi/10.1021/acsomega.3c01988

18. Al Aboud DM, Gossman W. Wood’s Light [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [Citado 02/06/2023]. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/30014596

19. Sanmiguel D. Dermatofitosis: claves diagnosticas en la consulta dermatológica. Dermatología [Internet]. Wallingford: CABI Digital library; 2020 [Citado 02/06/2023]. Disponible en: https://www.cabidigitallibrary.org/doi/pdf/10.5555/20203417496

20. CLSI. M38: Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. 3 ed [Internet]. Pennsylvania: Clin Lab Stand Inst; 2017 [Citado 02/06/2023]. Disponible en: https://clsi.org/media/1894/m38ed3_sample.pdf

21. Patel A. Dermatología de pequeños animales. Soluciones Saunders en la práctica Vet [Internet]. España: Elsevier España; 2010 [Citado 02/06/2023] Disponible en: https://books.google.de/books?id=mGVVzHRQexAC

22. Paulussen C, Hallsworth JE, Álvarez-Pérez S, Nierman WC, Hamill PG, Blain D, et al. Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. Microb Biotechnol [Internet]. 2017 Mar [Citado 02/06/2023];10(2):296–322. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/27273822

23. Simões D, de Andrade E, Sabino R. Fungi in a One Health Perspective. Encyclopedia [Internet]. 2023 Jul 23 [Citado 02/06/2023];3(3):900–18. Disponible en: https://www.mdpi.com/2673-8392/3/3/64

24. Xing H, Wang J, Sun Y, Wang H. Recent Advances in the Allergic Cross-Reactivity between Fungi and Foods. J Immunol Res [Internet]. 2022 [Citado 02/06/2023];2022:7583400. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/36249419

25. Kidd S. Descriptions of medical fungi. En su: Fungus [Internet]. Australia: Adelaide; 2016 [Citado 02/06/2023]. Disponible en: https://www.adelaide.edu.au/mycology/ua/media/1596/fungus3-book.pdf

26. Ramos‐García B, Abreu Hernández S, Fraga Ruíz S, Meléndez Ferrer O, Castañeda Ruíz RF. Diversity of keratinophilic fungi present in nine areas of horticultural production of the Habana County, Cuba. Rev Cubana Ciencias Biológicas. 2023;9(2).

27. Sarmiento MM, Mangiaterra M, Bojanich MV, Basualdo JÁ, Giusiano G. Hongos queratinofílicos en suelos de parques de la ciudad de Corrientes, Argentina. Rev Iberoam Micol [Internet]. 2016 Jan [Citado 02/06/2023];33(1):7–12. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1130140615000352

28. Ledezma E, Teresa Maniscalchi M, Lemus Espinoza D. Sinergismo entre ajoeno y ketoconazol en aislamientos de Microsporum canis. Un estudio preliminar mediante la determinación de la concentración inhibitoria fraccional (CIF). Rev Iberoam Micol [Internet]. 2008 Sep [Citado 02/06/2023];25(3):157–62. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S1130140608700378

29. Naeem Jasim NA, Al-humairi RM, Hashim Mohammad TA, Hussein R. Synergistic Treatment of Candida albicans Infected Mice by AgNPs Synthesis Penicillium chrysogenum. Bionatura [Internet]. 2023 Aug 15 [Citado 02/06/2023];8(CSS1):1–10. Disponible en: https://www.revistabionatura.com/files/2023.08.01.67.pdf

30. Fernández-Torres B, Inza I, Guarro J. Comparison of in vitro antifungal susceptibilities of conidia and hyphae of dermatophytes with thick-wall macroconidia. Antimicrob Agents Chemother [Internet]. 2003 Oct [Citado 02/06/2023];47(10):3371–2. Disponible en: http://www.ncbi.nlm.nih.gov/pubmed/14506062

31. Guzmán E, Ortega F, Rubio RG. Pickering Emulsions: A Novel Tool for Cosmetic Formulators. Cosmetics [Internet]. 2022 Jun 27 [Citado 02/06/2023];9(4):68. Disponible en: https://www.mdpi.com/2079-9284/9/4/68

32. Fernández-montes EA. Recursos tecnológicos y procedimientos en formulación magistral dermatológica. Farm Prof. 2012;26(2).

33. de Oliveira Ferreira A. Excipientes y Adyuvantes Farmacotécnicos. Excipientes Farm [Internet]. 2015 [Citado 02/06/2023];2. Disponible en: https://dokumen.tips/documents/excipientes-e-adjuvantes-farmacotecnicos.html

34. Alía E. Estudio de la Eficacia de Sistemas Antioxidantes en una emulsión de hidroquinona al 5%. Formulación Magistral [Internet]. 2012 [Citado 02/06/2023];29. Disponible en: http://www.formulacionmagistral.org/wp-content/uploads/INVESTIGACION-HIDROQUINONA-DR-ALIA.pdf

35. Suschka S, Fladung BF, Merk H. Clinical comparison of the efficacy and tolerability of once daily Canesten ® with twice daily Nizoral ® (clotrimazole 1% cream vs . ketoconazole 2% cream) during a 28‐day topical treatment of interdigital tinea pedis. Mycoses [Internet]. 2002 Apr 16 [Citado 02/06/2023];45(3–4):91–6. Disponible en: https://onlinelibrary.wiley.com/doi/10.1046/j.1439-0507.2002.00724.x

Published

2024-07-31

How to Cite

1.
Basantes Vaca CV, Parra Álvarez PF, Serrano Torres GJ, Torres Rodríguez SH, Navarrete Reino LM. Evaluation of the antifungal activity of ketoconazole against strains of Microsporum sp. and development of a pharmaceutical cream formulation. Rev haban cienc méd [Internet]. 2024 Jul. 31 [cited 2025 Jul. 6];23:e5752. Available from: https://revhabanera.sld.cu/index.php/rhab/article/view/5752

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Section

Biomedical Basic Sciences