High prevalence of itraconazole resistance among Candida parapsilosis isolated from Iran

Document Type : Short Communication


1 Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran

2 Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran

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

4 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

5 Faculty of Medicine, Sari Branch, Islamic Azad University, Sari, Iran

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


Background and Purpose: Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical C. parapsilosis against available azole antifungal drugs.
Materials and Methods: This study was conducted on 105 previously-identified isolates of C. parapsilosis sensu stricto. For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents.
Results: According to the results, 89% (n=94) of C. parapsilosis isolates showed a MIC of ≥ 1 μg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC50 values of 0.5 and 1 μg/ml, respectively.
Conclusion: The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.
Background and Purpose: Although Candida parapsilosis isolates have usually low MICs against azoles but recent study confirmed Candida –related invasive infections due to azoles resistance C. parapsilosis isolates. The main aim of this study was to determine the susceptibility pattern of Iranian clinical C. parapsilosis against available azolesantifungal drugs. .
Material and Methods: One hundred and five previously-identified isolates of C. parapsilosis sensu stricto were subjected to antifungal susceptibility testing against fluconazole, itraconazole, voriconazole and two new azole drugs, loliconazole and lanoconazole using the broth microdilution reference method according to CLSI M27-A3 and M27-S4 document.
Results: Eighty nine percent (n=94) of C. parapsilosis isolates showed MIC ≥ 1µg/ml which indicated resistance against itraconazole. Multi-azoles resistances were observed in 3.8% of the isolates. Loliconazole and lanoconazole demonstrated the highest efficacy with MIC50 values of 0.5 and 1µg/ml, respectively.
Conclusion: The majority of the isolates showed high MIC values against Itraconazole. It may associated with the long term Itraconazole prophylaxis/therapy in patients Infected with candidasis. Hence, choosing the appropriate antifungal is the crucial step for starting treatment.


1. Messer SA, Jones RN, Fritsche TR. International surveillance of Candida spp. and Aspergillus spp.: report from the SENTRY Antimicrobial Surveillance Program (2003). J Clin Microbiol. 2006; 44(5):1782-7.
2. Oberoi JK. Invasive candidasis. JIMSA. 2010; 23(1):25-8.
3. Pfaller M, Neofytos D, Diekema D, Azie N, Meier-Kriesche H-U, Quan SP, et al. Epidemiology and outcomes of candidemia in 3648 patients: data from the Prospective Antifungal Therapy (PATH Alliance®) registry, 2004–2008. Diagn Microbiol Infect Dis. 2012; 74(4):323-31.
4. Lotfi N, Shokohi T, Nouranibaladezaei SZ, Omran AN, Kondori N. High recovery rate of non-albicans Candida species isolated from burn patients with candidemia in Iran. Jundishapur J Microbiol. 2015; 8(10):e22929.
5. Kołaczkowska A, Kołaczkowski M. Drug resistance mechanisms and their regulation in non-albicans Candida species. J Antimicrob Chemother. 2016; 71(6):1438-50.
6. Garzillo C, Bagattini M, Bogdanović L, Di Popolo A, Iula VD, Catania MR, et al. Risk factors for Candida parapsilosis bloodstream infection in a neonatal intensive care unit: a case-control study. Ital J Pediatr. 2017; 43(1):10.
7. Lan YB, Huang YZ, Qu F, Li JQ, Ma LJ, Yan J, Zhou JH. Time course of global gene expression alterations in Candida albicans during infection of HeLa cells. Bosnian J Basic Med Sci. 2017;17(2):120-31.
8. 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.
9. Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by the infectious diseases society of America. Clin Infect Dis. 2009; 48(5):503-35.
10. Souza ACR, Fuchs BB, Pinhati HM, Siqueira RA, Hagen F, Meis JF, et al. Candida parapsilosis resistance to fluconazole: molecular mechanisms and in vivo impact in infected Galleria mellonella larvae. Antimicrob Agents Chemother. 2015; 59(10):6581-7.
11. Moudgal V, Little T, Boikov D, Vazquez JA. Multiechinocandin-and multiazole-resistant Candida parapsilosis isolates serially obtained during therapy for prosthetic valve endocarditis. Antimicrob Agents Chemother. 2005; 49(2):767-9.
12. Grant SM, Clissold SP. Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs. 1989; 37(3):310-44.
13. Hedayati MT, Tavakoli M, Zakavi F, Shokohi T, Mofarrah R, Ansari S, et al. In vitro antifungal susceptibility of Candida speciesisolated from diabetic patients. Rev Soc Bras Med Trop. 2018; 51(4):542-5.
14. Abastabar M, Al-Hatmi AM, Moghaddam MV, de Hoog GS, Haghani I, Aghili SR, et al. Potent activity of luliconazole, lanoconazole and eight comparators against molecularly
characterized fusarium species. Antimicrob Agents Chemother. 2018; 62(5):e00009-18.
15. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. using clinical and laboratory standards institute broth microdilution methods, 2010-2012. J Clin Microbiol. 2012; 50(9):2846-56.
16. Hiranandani M, Singhi S, Kaur I, Chakrabarti A. Disseminated nosocomial candidiasis in a pediatric intensive care unit. Indian Pediatr. 1995; 32(11):1160-6.
17. Tosti A, Piraccini BM, Lorenzi S, Iorizzo M. Treatment of nondermatophyte mold and Candida onychomycosis. Dermatol Clin. 2003; 21(3):491-7.
18. Gupta AK, Shear NH. A risk-benefit assessment of the newer oral antifungal agents used to treat onychomycosis. Drug Saf. 2000; 22(1):33-52.
19. Clark TA, Slavinski SA, Morgan J, Lott T, Arthington-Skaggs BA, Brandt ME, et al. Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital. J Clin Microbiol. 2004; 42(10):4468-72.
20. Ruiz L, Khouri S, Hahn RC, da Silva EG, de Oliveira VKP, Gandra RF, et al. Candidemia by species of the Candida parapsilosis complex in children’s hospital: prevalence, biofilm production and antifungal susceptibility. Mycopathologia. 2013; 175(3-4):231-9.
21. Sojakova M, Liptajova D, Borovsky M, Subik J. Fluconazole and itraconazole susceptibility of vaginal yeast isolates from Slovakia. Mycopathologia. 2004; 157(2):163-9.
22. Mondal RK, Singhi SC, Chakrabarti A, Jayashree M. Randomized comparison between fluconazole and itraconazole for the treatment of candidemia in a pediatric intensive care unit: a preliminary study. Pediatr Crit Care Med. 2004; 5(6):561-5.
23. Cantón E, Pemán J, Quindós G, Eraso E, Miranda-Zapico I, Álvarez M, et al. Epidemiology, molecular identification and antifungal susceptibility of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis isolated from patients with candidemia: prospective multicenter study. Antimicrob Agents Chemother. 2011; 55(12):5590-6.
24. Pfaller MA, Messer SA, Woosley LN, Jones RN, Castanheira M. Echinocandin and triazole antifungal susceptibility profiles of opportunistic yeast and mould clinical isolates (2010-2011): application of new CLSI clinical breakpoints and epidemiological cutoff values to characterize geographic and temporal trends of antifungal resistance. J Clin Microbiol. 2013; 51(8):2571-81.
25. Lotfali E, Kordbacheh P, Mirhendi H, Zaini F, Ghajari A, Mohammadi R, et al. Antifungal susceptibility analysis of clinical isolates of Candida parapsilosis in Iran. Iran J Public Health. 2016; 45(3):322-8.
26. Castanheira M, Deshpande LM, Davis AP, Rhomberg PR, Pfaller MA. Monitoring antifungal resistance in a global collection of invasive yeasts and moulds: application of CLSI epidemiological cutoff values and whole genome sequencing analysis for detection of azole resistance in Candida albicans. Antimicrob Agents Chemother. 2017; 61(10):e00906-17.
27. Mohamadi J, Havasian MR, Panahi J, Pakzad I. Antifungal drug resistance pattern of Candida. spp isolated from vaginitis in Ilam-Iran during 2013-2014. Bioinformation. 2015; 11(4):203-6.
28. Goldman M, Cloud GA, Smedema M, LeMonte A, Connolly P, McKinsey DS, et al. Does long-term itraconazole prophylaxis result in in vitro azole resistance in mucosal Candida albicans isolates from persons with advanced human immunodeficiency virus infection? Antimicrob Agents Chemother. 2000; 44(6): 1585-7.
Volume 5, Issue 3
September 2019
Pages 43-46
  • Receive Date: 08 July 2019
  • Revise Date: 20 September 2019
  • Accept Date: 06 October 2019
  • First Publish Date: 06 October 2019