In vitro antifungal susceptibilities of six antifungal drugs against clinical Candida glabrata isolates according to EUCAST

Document Type : Original Articles


1 Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Medical Mycology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


Background and Purpose: Candida glabrata is the second cause of candidiasis. The mortality rate of C. glabrata infections is about 40%; accordingly, it may be life threatening, especially in immunocompromised hosts. Regarding this, the current study was conducted to evaluate the regional patterns of the antifungal susceptibility of clinical C. glabrata isolated from the patients referring to the health centers located in Ahvaz, Iran.
Materials and Methods: In this study, a total of 30 clinical strains of C. glabrata isolates were recovered from different body sites (i.e., vagina, mouth, and urine). Phenotypic characteristics and molecular methods were used to identify the isolates. The minimum inhibitory concentration (MIC) was determined according to the European Committee on Antimicrobial Susceptibility Testing.
Results: Our findings demonstrated that 20%, 80%, and 6.7% of the isolates were resistant to amphotericin B, terbinafine, and posaconazole, respectively, while all the isolates were found to be fluconazole susceptible dose dependent and susceptible to voriconazole and caspofungin.
Conclusion: Our study suggested that voriconazole had high potency against C. glabrata isolates. Consequently, this antifungal agent can be an alternative drug in the treatment of resistant patients. These results can be helpful for the successful treatment of patients in different regions.


1. Shigemura K, Osawa K, Jikimoto T, Yoshida H, Hayama B, Ohji G, et al. Comparison of the clinical risk factors between Candida albicans and Candida non-albicans species for bloodstream infection. J Antibiot. 2014; 67(4):311-4.
2. Szweda P, Gucwa K, Romanowska E, Dzierz Anowska-Fangrat K, Naumiuk Ł, Brillowska-Da Browska A, et al. Mechanisms of azole resistance among clinical isolates of Candida glabrata in Poland. J Med Microbiol. 2015; 64(6):610-9.
3. Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010; 23(2):253-73.
4. Bialkova A, Šubík J. Biology of the pathogenic yeast Candida glabrata. Folia Microbiol. 2006; 51(1):3-20.
5. Leite Júnior DP, Yamamoto AC, Martins ER, Teixeira AF, Hahn RC. Species of Candida isolated from anatomically distinct sites in military personnel in Cuiabá, Mato Grosso, Brazil. An Bras Dermatol. 2011; 86(4):675-80.
6. Deorukhkar SC, Saini S, Mathew S. Non-albicans Candida infection: an emerging threat. Interdiscip Perspect Infect Dis. 2014; 2014:615958.
7. Lamoth F, Lockhart SR, Berkow EL, Calandra T. Changes in the epidemiological landscape of invasive candidiasis. J Antimicrob Chemother. 2018; 73(Suppl 1):i4-13.
8. Biswas C, Marcelino VR, Van Hal S, Halliday C, Martinez E, Wang Q, et al. Whole genome sequencing of Australian Candida glabrata isolates reveals genetic diversity and novel sequence types. Front Microbiol. 2018; 9:2946.
9. Esfandiary MA, Farasat A, Rostamian M, Fattahy A. Study of morphological characteristics, pathogenicity and drug resistance of Candida glabrata as increasing opportunistic yeast. Eur J Exper Biol. 2012; 2(4):948-52.
10. Nash EE, Peters BM, Lilly EA, Noverr MC, Fidel PL Jr. A murine model of Candida glabrata vaginitis shows no evidence of an inflammatory immunopathogenic response. PLoS One. 2016; 11(1):e0147969.
11. Mota S, Alves R, Carneiro C, Silva S, Brown AJ, Istel F, et al. Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate. Fron Microbiol. 2015; 6:919.
12. Fidel PL, Vazquez JA, Sobel JD. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev. 1999; 12(1):80-96.
13. Kumar K, Askari F, Sahu MS, Kaur R. Candida glabrata: a lot more than meets the eye. Microorganisms. 2019; 7(2):E39.
14. Pais P, Galocha M, Viana R, Cavalheiro M, Pereira D, Teixeira MC. Microevolution of the pathogenic yeasts Candida albicans and Candida glabrata during antifungal therapy and host infection. Microbial Cell. 2019; 6(3):142-59.
15. Fernández-Silva F, Lackner M, Capilla J, Mayayo E, Sutton D, Castanheira M, et al. In vitro antifungal susceptibility of Candida glabrata to caspofungin and the presence of FKS mutations correlate with treatment response in an immunocompromised murine model of invasive infection. Antimicrob Agents Chemother. 2014; 58(7):3646-9.
16. Nagayoshi Y, Miyazaki T, Shimamura S, Nakayama H, Minematsu A, Yamauchi S, et al. Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species. PloS One. 2017; 12(7):e0180990.
17. Lindberg E, Hammarström H, Ataollahy N, Kondori N. Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Sci Rep. 2019; 9(1):3838.
18. Fatahinia M, Halvaeezadeh M, Rezaei-Matehkolaei A. Comparison of enzymatic activities in different Candida species isolated from women with vulvovaginitis. J Mycol Med. 2017; 27(2):188-94.
19. Zarei Mahmoudabadi A, Rezaei-Matehkolaei A, Navid M, Torabizadeh M, Mazdarani S. Colonization and antifungals susceptibility patterns of Candida species isolated from hospitalized patients in ICUs and NICUs. J Nephropathol. 2015; 4(3):77-84.
20. Fatahinia M, Poormohamadi F, Zarei Mahmoudabadi A. Comparative study of esterase and hemolytic activities in clinically important Candida species, isolated from oral cavity of diabetic and non-diabetic individuals. Jundishapur J Microbiol. 2015; 8(3):e20893.
21. Workowski KA. Centers for disease control and prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis. 2015; 61(Suppl 8):S759-62.
22. Silva GA, Bernardi TL, Schaker PD, Menegotto M, Valente P. Rapid yeast DNA extraction by boiling and freeze-thawing without using chemical reagents and DNA purification. Braz Arch Biol Technoly. 2012; 55(2):319-27.
23. Merseguel KB, Nishikaku AS, Rodrigues AM, Padovan AC, e Ferreira RC, de Azevedo Melo AS, et al. Genetic diversity of medically important and emerging Candida species causing invasive infection. BMC Infect Dis. 2015; 15:57.
24. Gharaghani M, Rezaei-Matehkolaei A, Zarei Mahmoudabadi A, Keikhaei B. The frequency, antifungal susceptibility and enzymatic profiles of Candida species isolated from neutropenic patients. Jundishapur J Microbiol. 2016; 9(11):e60179.
25. Hoang MTV, Irinyi L, Chen SCA; ISHAM Barcoding of Medical Fungi Working Group, Meyer W. Dual DNA barcoding for the molecular identification of the agents of invasive fungal infections. Front Microbiol. 2019; 10:1647.
26. Meletiadis J, Curfs-Breuker I, Meis JF, Mouton JW. In vitro antifungal susceptibility testing of Candida isolates with the EUCAST methodology, a new method for ECOFF determination. Antimicrob Agents Chemother. 2017; 61(4): e02372-16.
27. Jamil NI, Wahab WN, Ali IA, Yahaya ML. Direct resazurin microplate assay in drug susceptibility testing of smear-positive sputum samples against mycobacterium tuberculosis. Malays J Med Sci. 2018; 25(6):59-66.
28. Kiasat N, Rezaei-Matehkolaei A, Mahmoudabadi AZ. Microsatellite typing and antifungal susceptibility of Candida
glabrata strains isolated from patients with Candida vaginitis. Front Microbiol. 2019; 10:1678.
29. Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med. 2012; 125(1 Suppl):S3-13.
30. Abaci O, Haliki-Uztan A. Investigation of the susceptibility of Candida species isolated from denture wearers to different antifungal antibiotics. Afr J Microbiol Res. 2011; 5(12):1398-403.
31. Orasch C, Marchetti O, Garbino J, Schrenzel J, Zimmerli S, Mühlethaler K, et al. Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland. Clin Microbiol Infect. 2014; 20(7):698-705.
32. Arendrup MC, Patterson TF. Multidrug-resistant Candida: epidemiology, molecular mechanisms, and treatment. J Infect Dis. 2017; 216(Suppl 3):S445-51.
33. Sharifzadeh A, Khosravi AR, Shokri H, Sharafi G. Antifungal effect of Trachyspermum ammi against susceptible and fluconazole-resistant strains of Candida albicans. J Mycol Med. 2015; 25(2):143-50.
34. Ramsay S, Astill N, Shankland G, Winter A. Practical management of recurrent vulvovaginal candidiasis. Trends Urol Gynaecol Sex Health. 2009; 14(6):18-22.
35. 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.
36. Yang YL, Li SY, Cheng HH, Lo HJ. The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan. BMC Infect Dis. 2005; 5(1):99.
37. Badiee P, Badali H, Boekhout T, Diba K, Moghadam AG, Nasab AH, 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.
38. Mahdavi Omran S, Rezaei Dastjerdi M, Zuashkiani M, Moqarabzadeh V, Taghizadeh-Armaki M. In vitro antifungal susceptibility of Candida species isolated from Iranian patients with denture stomatitis. Biomed Res Int. 2018; 2018:3086586.
39. Ryder NS, Wagner S, Leitner I. In vitro activities of terbinafine against cutaneous isolates of Candida albicans and other pathogenic yeasts. Antimicrob Agents Chemother. 1998; 42(5):1057-61.
40. Morales-López SE, Taverna CG, Bosco-Borgeat ME, Maldonado I, Vivot W, Szusz W, et al. Candida glabrata species complex prevalence and antifungal susceptibility testing in a culture collection: first description of Candida nivariensis in Argentina. Mycopathologia. 2016; 181(11-12):871-8.
41. Pfaller M, Diekema D, Jones R, Messer S, Hollis R. Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000. J Clin Microbiol. 2002; 40(3):852-6.
42. Pfaller M, Diekema D, Jones R, Sader HS, Fluit A, Hollis R, et al. International surveillance of bloodstream infections due Tocandida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program. J Clin Microbiol. 2001; 39(9):3254-9.
43. Singh S, Nawange SR, Warthe N. In-vitro antifungal susceptibility reveals occurrence of Azole and Allylamine resistance among clinical isolates of Candida albicans and Candida non albicans from central India. Int J Pharm Sci Res. 2014; 5(12):5267-75.
44. Alborzi A, Davarpanah MA. Distributions and antifungal susceptibility of Candida species from mucosal sites in HIV positive patients. Arch Iran Med. 2010; 13(4):282-7.
45. Labbé AC, Pépin J, Patiño C, Castonguay S, Restieri C, Laverdiere M. A single-centre 10-year experience with Candida bloodstream infections. Can J Infect Dis Med Microbiol. 2009; 20(2):45-50.
46. Arastehfar A, Daneshnia F, Zomorodian K, Najafzadeh MJ, Khodavaisy S, Zarrinfar H, et al. Low level of antifungal resistance in Iranian isolates of Candida glabrata recovered from blood samples in a multicenter study from 2015 to 2018 and potential prognostic values of genotyping and sequencing of PDR1. Antimicrob Agents Chemother. 2019; 63(7):e02503-18.
47. Espinel-Ingroff A, Barchiesi F, Cuenca-Estrella M, Pfaller M, Rinaldi M, Rodriguez-Tudela J, et al. International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole. J Clin Microbiol. 2005; 43(8):3884-9.
48. Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015; 64(RR-03):1-137.
Volume 6, Issue 2
June 2020
Pages 1-6
  • Receive Date: 20 September 2019
  • Revise Date: 30 December 2019
  • Accept Date: 07 March 2020
  • First Publish Date: 01 June 2020
  • Publish Date: 01 June 2020