In vitro activity of four triazole antifungal drugs against clinically common and uncommon yeast species

Document Type : Original Articles


1 Infectious and Tropical Diseases Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran

2 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Medical Immunology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran

4 Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Internal Medicine, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran

6 Department of Public Health, School of Health, Fasa University of Medical Sciences, Fasa, Iran

7 Department of Medical Mycology and Parasitology, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran


Background and Purpose: Incidence of fungal infections caused by opportunistic fungal pathogens, such as yeasts and yeast-like species, has undergone an increase in otherwise healthy individuals. These pathogens account for high mortality and show reduced susceptibility to the routine antifungal drugs. Accordingly, antifungal susceptibility testing is an urgent need in the determination of the susceptibility spectrum of antifungals and selection of appropriate antifungal agents for the management of patients with fungal infection.
Materials and Methods: The present study was conducted on 110 yeast strains belonging to 15 species recovered from clinical specimens. Susceptibility of the isolates to four antifungal drugs (i.e., fluconazole, itraconazole, voriconazole, and posaconazole) was tested according to the Clinical and Laboratory Standards Institute guidelines M27-A3 and M27-S4.
Results: Fluconazole exhibited no activity against 4.3% (n=2) of C. albicans isolates, whereas the remaining 44 isolates had a minimum inhibitory concentration (MIC) range of 0.125-4 μg/ml. Voriconazole had the lowest geometric mean MIC (0.03 μg/ml) against all isolated yeast species, followed by posaconazole (0.07 μg/ml), itraconazole (0.10 μg/ml), and fluconazole (0.60 μg/ml). Overall, all of the isolates had reduced voriconazole MICs with a MIC range of 0.016-0.5 μg/ml, except for one isolate of C. albicans that had a MIC of 1 μg/ml. Candida haemulonii as a multidrug-resistant fungus showed a fluconazole MIC of > 64 μg/ml.
Conclusion: The current study provides insight into the antifungal susceptibility profiles of clinically common and uncommon yeast species to four triazole antifungal agents. According to our findings, voriconazole was the most active agent. Awareness about antifungal susceptibility patterns is highly helpful in the selection of appropriate antifungal drugs and identification of the efficiency of the currently used agents.


1. Afsarian MH, Badali H, Boekhout T, Shokohi T, Katiraee F. Multilocus sequence typing of Candida albicans isolates from a burn intensive care unit in Iran. J Med Microbiol. 2015; 64(Pt 3):248-53.
2. Rezazadeh E, Sabokbar A, Moazeni M, Rezai MS, Badali H. Microdilution in vitro antifungal susceptibility patterns of Candida species, from mild cutaneous to bloodstream infections. Jundishapur J Microbiol. 2016; 9(7):e34151.
3. Afsarian SM, Badali H, Shokohi T, Najafipour S. Molecular diversity of Candida albicans isolated from immunocompromised patients, based on MLST method. Iran J Public Health. 2015; 44(9):1262-9.
4. Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, et al. Multidrug-resistant candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization-time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by vitek 2, CLSI broth microdilution, and etest method. J Clin Microbiol. 2015; 53(6):1823-30.
5. Tekarslan-Sahin SH, Alkim C, Sezgin T. Physiological and transcriptomic analysis of a salt-resistant Saccharomyces cerevisiae mutant obtained by evolutionary engineering. Bosnian J Basic Med Sci. 2018; 18(1):55.
6. Aslani N, Janbabaei G, Abastabar M, Meis JF, Babaeian M, Khodavaisy S, et al. Identification of uncommon oral yeasts from cancer patients by MALDI-TOF mass spectrometry. BMC Infect Dis. 2018; 18(1):24.
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. Chandrasekar P. Management of invasive fungal infections: a role for polyenes. J Antimicrob Chemother. 2011; 66(3):457-65.
9. Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ, Lortholary O, et al. ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect. 2012; 18(Suppl 7):19-37.
10. Rogers TR. Antifungal drug resistance: limited data, dramatic impact? Int J Antimicrob Agents. 2006; 27(Suppl 1):7-11.
11. Capoor MR, Nair D, Deb M, Verma PK, Srivastava L, Aggarwal P. Emergence of non-albicans Candida species and antifungal resistance in a tertiary care hospital. Jpn J Infect Dis. 2005; 58(6):344-8.
12. Shokohi T, Moradi N, Badram L, Badali H, Ataollahi MR, Afsarian MH. Molecular identification of clinically common and uncommon yeast species. Jundishapur J Microbiol. 2018; 11(10):e66240.
13. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard-third edition, M27–A3. Wayne: CLSI; 2008.
14. Clinical and Laboratory Standards Institute (CLSI). Reference method for broth dilution antifungal susceptibility testing of yeasts: fourth informational supplement M27-S4. Wayne: CLSI; 2012.
15. Guo F, Yang Y, Kang Y, Zang B, Cui W, Qin B, et al. Invasive candidiasis in intensive care units in China: a multicentre prospective observational study. J Antimicrob Chemother. 2013; 68(7):1660-8.
16. Hu L, Du X, Li T, Song Y, Zai S, Hu X, et al. Genetic and phenotypic characterization of Candida albicans strains isolated from infectious disease patients in Shanghai. J Med Microbiol. 2015; 64(Pt 1):74-83.
17. Falagas ME, Roussos N, Vardakas KZ. Relative frequency of albicans and the various non-albicans Candida spp among candidemia isolates from inpatients in various parts of the world: a systematic review. Int J Infect Dis. 2010; 14(11):e954-66.
18. Vazquez JA. Invasive fungal infections in the intensive care unit. Semin Respir Crit Care Med. 2010; 31(1):79-86.
19. Shi C, Liu C, Liu J, Wang Y, Li J, Xiang M. Anti-Candida activity of new azole derivatives alone and in combination with fluconazole. Mycopathologia. 2015; 180(3-4):203-7.
20. Almeida AA, Mesquita CS, Svidzinski TI, Oliveira KM. Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil. Rev Soc Bras Med Trop. 2013; 46(3):335-9.
21. Eksi F, Gayyurhan ED, Balci I. In vitro susceptibility of Candida species to four antifungal agents assessed by the reference broth microdilution method. Sci World J. 2013; 2013:236903.
22. Bhattacharjee P. Epidemiology and antifungal susceptibility of Candida species in a tertiary care hospital, Kolkata, India. Curr Med Mycol. 2016; 2(2):20-7.
23. Badiee P, Alborzi A, Shakiba E, Farshad S, Japoni A. Susceptibility of Candida species isolated from immunocompromised patients to antifungal agents. East Mediterr Health J. 2011; 17(5):425-30.
24. Wisplinghoff H, Ebbers J, Geurtz L, Stefanik D, Major Y, Edmond MB, et al. Nosocomial bloodstream infections due to Candida spp. in the USA: species distribution, clinical features and antifungal susceptibilities. Int J Antimicrob Agents. 2014; 43(1):78-81.
25. Castanheira M, Messer SA, Rhomberg PR, Pfaller MA. Antifungal susceptibility patterns of a global collection of fungal isolates: results of the SENTRY Antifungal Surveillance Program (2013). Diagn Microbiol Infect Dis. 2016; 85(2):200-4.
26. Whaley SG, Berkow EL, Rybak JM, Nishimoto AT, Barker KS, Rogers PD. Azole antifungal resistance in Candida albicans and emerging non-albicans Candida Species. Front Microbiol. 2016;
27. Kanafani ZA, Perfect JR. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin Infect Dis. 2008; 46(1):120-8.
28. Haddadi P, Zareifar S, Badiee P, Alborzi A, Mokhtari M, Zomorodian K, et al. Yeast colonization and drug susceptibility pattern in the pediatric patients with neutropenia. Jundishapur J Microbiol. 2014; 7(9):e11858.
29. Badiee P, Badali H, Boekhout T, Diba K, Moghadam AG, Hossaini Nasab A, et al. Antifungal susceptibility testing of Candida species isolated from the immunocompromised patients admitted to ten university hospitals in Iran: comparison of colonizing and infecting isolates. BMC Infect Dis. 2017; 17(1):727.
30. Bassetti M, Taramasso L, Nicco E, Molinari MP, Mussap M, Viscoli C. Epidemiology, species distribution, antifungal susceptibility and outcome of nosocomial candidemia in a tertiary care hospital in Italy. PLoS One. 2011; 6(9):e24198.
31. Shokohi T, Bandalizadeh Z, Hedayati MT, Mayahi S. In vitro antifungal susceptibility of Candida species isolated from oropharyngeal lesions of patients with cancer to some antifungal agents. Jundishapur J Microbiol. 2011; 4(2):S19-26.
32. Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009. Antimicrob Agents Chemother. 2011; 55(2):561-6.
33. Yenisehirli G, Ozveren G, Yenisehirli A, Bulut Y. In Vitro susceptibilities of non-albicans Candida species to echinocandins, Azoles, and Amphotericin B in Tokat, Turkey. Jundishapur J Microbiol. 2018; 11(6):e59404.
34. Seifert H, Aurbach U, Stefanik D, Cornely O. In vitro activities of isavuconazole and other antifungal agents against Candida bloodstream isolates. Antimicrob Agents Chemother. 2007; 51(5):1818-21.
35. Shokohi T, Badali H, Amirrajab N, Ataollahi MR, Kouhpayeh SA, Afsarian MH. In vitro activity of five antifungal agents against Candida albicans isolates, Sari, Iran. Curr Med Mycol. 2016; 2(2):34-9.
36. Amirrajab N, Badali H, Didehdar M, Afsarian MH, Mohammadi R, Lotfi N, et al. In Vitro activities of six antifungal drugs against Candida glabrata isolates: an emerging pathogen. Jundishapur J Microbiol. 2016; 9(5):e36638.
37. Pfaller MA, Rhomberg PR, Messer SA, Jones RN, Castanheira M. Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cutoff values. Diagn Microbiol Infect Dis. 2015; 82(4):303-13.
38. Badiee P, Badali H, Diba K, Jafarian H, Mohammadi R, Mirhendi H, et al. Multicenter identification and antifungal susceptibility patterns of candida species isolated from clinical samples. Jundishapur J Microbiol. 2017; 10(12):e56117.
39. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007; 20(1):133-63.
Volume 5, Issue 4
December 2019
Pages 14-19
  • Receive Date: 31 May 2019
  • Revise Date: 27 August 2019
  • Accept Date: 04 September 2019
  • First Publish Date: 01 December 2019