Species distribution and susceptibility profiles of Candida species isolated from vulvovaginal candidiasis, emergence of C. lusitaniae

Document Type : Original Articles

Authors

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

2 Invasive Fungi Research Centre (IFRC), 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 Gynecology and Obstetrics Department of Hazrat-e- Zainab Hospital, Babolsar, Iran.

Abstract

Background and Purpose: The aim of the current study was to investigate the epidemiology of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC), as well as the antifungal susceptibility patterns of Candida species isolates.
Materials and Methods: A cross-sectional study was carried out on 260 women suspected of VVC from February 2017 to January 2018. In order to identify Candida species isolated from the genital tracts, the isolates were subjected to polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using enzymes Msp I and sequencing. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute guidelines (M27-A3).
Results: Out of 250 subjects, 75 (28.8%) patients were affected by VVC, out of whom 15 (20%) cases had RVVC. Among the Candida species, C. albicans was the most common species (42/95; 44.21%), followed by C. lusitaniae (18/95; 18.95%), C. parapsilosis (13/95; 13.69%),  C. glabrata (8/95; 8.42%), C. kefyr (6/95; 6.31%), C. famata (5/95; 5.26%), C. africana (2/95; 2.11%), and C. orthopsilosis (1/95; 1.05%), respectively. Multiple Candida species were observed in 28% (21/75) of the patients. Nystatin showed the narrowest range of minimum inhibitory concentration (MIC) (0.25-16 μg/ml) against all Candida strains, whereas fluconazole (0.063-64 μg/ml) demonstrated the widest MIC range. In the current study, C. lusitaniae, as the second most common causative agent of VVC, was susceptible to all antifungal agents. Furthermore, 61.1% of C. lusitaniae isolates were inhibited at a concentration of ≤ 2 μg/ml, while38.9% (n=7)of them exhibited fluconazole MICs above the epidemiologic cutoff values (ECV). Candida species showed the highest overall resistance against fluconazole (61.3%), followed by itraconazole (45.2%) and caspofungin (23.7%). All of C. albicans strains were resistant to itraconazole with a MIC value of ≥ 1 μg/ml; in addition, 87.5% of them were resistant to fluconazole. Moreover, 100% and 87.5% of C. glabrata strains were resistant to caspofungin and fluconazole, respectively.
Conclusion: As the findings revealed, the majority of VVC cases were caused by non-albicans Candida species which were often more resistant to antifungal agents. Candida lusitaniae generally had fluconazole MICs above the ECV. Given the propensity of C. lusitaniae to develop resistance under drug pressure, antifungals should be administered with caution. The emergence of these species justify the epidemiological surveillance surveys to watch out the distribution of yeast species.

Keywords

References

1. Richter SS, Galask RP, Messer SA, Hollis RJ, Diekema DJ, Pfaller MA. Antifungal susceptibilities of Candida species causing vulvovaginitis and epidemiology of recurrent cases. J Clin Microbiol. 2005; 43(5):2155-62.
2. Alizadeh M, Kolecka A, Boekhout T, Zarrinfar H, Ghanbari Nahzag MA, Badiee P, et al. Identification of Candida species isolated from vulvovaginitis using matrix assisted laser desorption ionization-time of flight mass spectrometry. Curr Med Mycol. 2017; 3(4):21-5.
3. Vandeven AM, Emans S. Vulvovaginitis in the child and adolescent. Pediatr Rev. 1993; 14(4):141-7.
4. Minooeianhaghighi MH, Sehatpour M, Shokri H. Determination of drug susceptibility of Candida strains isolated from patients with recurrent Candida vulvovaginitis and investigation of predisposing factors of the disease. Avicenna J Clin Med. 2017; 23(4):336-44.
5. Gonçalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol. 2016; 42(6):905-27.
6. Malazy OT, Shariat M, Heshmat R, Majlesi F, Alimohammadian M, Tabari NK, et al. Vulvovaginal candidiasis and its related factors in diabetic women. Taiwan J Obstet Gynecol. 2007; 46(4):399-404.
7. Noori M, Dakhili M, Sepahvand A, Davari N. Evaluation of esterase and hemolysin activities of different Candida species isolated from vulvovaginitis cases in Lorestan Province, Iran. Curr Med Mycol. 2017; 3(4):1-5.
8. Nazeri M, Mesdaghinia E, Moravej SA, Atabakhshiyan R, Soleymani F. Prevalence of vulvovaginal candidiasis and frequency of candida species in women. J Mazandaran Univ Med Sci. 2012; 21(86):254-62.
9. Dovnik A, Golle A, Novak D, Arko D, Takac I. Treatment of vulvovaginal candidiasis: a review of the literature. Acta Dermatovenerol Alp Pannonica Adriat. 2015; 24(1):5-7.
10. Khanmohamadi M, Mehbod AS, Noraeepour M, Didehdar M. Molecular identification of candida species isolated from women with vulvovaginal candidiasis: brief report. Tehran Univ Med J. 2017; 75(7):538-42.
11. Fornari G, Vicente VA, Gomes RR, Muro MD, Pinheiro RL, Ferrari C, et al. Susceptibility and molecular characterization of Candida species from patients with vulvovaginitis. Braz J Microbiol. 2016; 47(2):373-80. 12. Silverman NS, Morgan M, Nichols WS. Candida lusitaniae as an unusual cause of recurrent vaginitis and its successful treatment with intravaginal boric acid. Infect Dis Obstet Gynecol. 2001; 9(4):245-7.
13. Favel A, Michel-Nguyen A, Peyron F, Martin C, Thomachot L, Datry A, et al. Colony morphology switching of Candida lusitaniae and acquisition of multidrug resistance during treatment of a renal infection in a newborn: case report and review of the literature. Diagn Microbiol Infect Dis. 2003; 47(1):331-9.
14. Asner SA, Giulieri S, Diezi M, Marchetti O, Sanglard D. Acquired multidrug antifungal resistance in Candida lusitaniae during therapy. Antimicrob Agents Chemother. 2015; 59(12):7715-22.
15. Khosravi Rad K, Falahati M, Roudbary M, Farahyar S, Nami S. Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis. Curr Med Mycol. 2016; 2(4):24-29.
16. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2015; 62(4):e1-50.
17. Walker PP, Reynolds MT, Ashbee HR, Brown C, Evans EG. Vaginal yeasts in the era of “over the counter” antifungals. Sex Transm Infect. 2000; 76(6):437-8.
18. Rex JH, Rinaldi M, Pfaller M. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995; 39(1):1-8.
19. Sharifynia S, Falahati M, Akhlaghi L, Foroumadi A, Fateh R. Molecular identification and antifungal susceptibility profile of Candida species isolated from patients with vulvovaginitis in Tehran, Iran. J Res Med Sci. 2017; 22:132.
20. Didehdar M, Khansarinejad B, Amirrajab N, Shokohi T. Development of a high‐resolution melting analysis assay for rapid and high‐throughput identification of clinically important dermatophyte species. Mycoses. 2016; 59(7):442-9.
21. Shokohi T, Soteh MH, Pouri ZS, Hedayati M, Mayahi S. Identification of Candida species using PCR-RFLP in cancer patients in Iran. Indian J Med Microbiol. 2010; 28(2):147-51.
22. Romeo O, Criseo G. First molecular method for discriminating between Candida africana, Candida albicans, and Candida dubliniensis by using hwp1 gene. Diagn Microbiol Infect Dis. 2008; 62(2):230-3.
23. Abastabar M, Hosseinpoor S, Hedayati MT, Shokohi T, Valadan R, Mirhendi H, et al. Hyphal wall protein 1 gene: a potential marker for the identification of different Candida species and phylogenetic analysis. Curr Med Mycol. 2016; 2(4):1-8.
24. Rex JH, Alexander BD, Andes D, Arthington-Skaggs B, Brown SD, Chaturveli V, et al. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi: CLSI document M38–A2. Wayne, PA, USA: Clinical and Laboratory Standards Institute; 2008.
25. Santos ER, Dal Forno CF, Hernandez MG, Kubiça TF, Venturini TP, Chassot F, et al. Susceptibility of Candida spp. isolated from blood cultures as evaluated using the M27-A3 and new M27-S4 approved breakpoints. Rev Inst Med Trop Sao Paulo. 2014; 56(6):477-82.
26. Abbasi Nejat Z, Farahyar S, Falahati M, Khozani M, Hosseini A, Faiazy A, et al. Molecular identification and antifungal susceptibility pattern of non-albicans candida species isolated from vulvovaginal candidiasis. Iran Biomed J. 2018; 22(1):33-41.
27. Diba K, Namaki A, Ayatolahi H, Hanifian H. Comparison of biochemical and molecular methods for the identification of candida species causing vulvovaginal candidiasis and recurring vulvovaginal candidiasis. Iran J Med Microbiol.
2014; 8(3):45-50.
28. Hedayati MT, Taheri Z, Galinimoghadam T, Aghili SR, Yazdani Cherati J, Mosayebi E. Isolation of different species of Candida in patients with vulvovaginal candidiasis from Sari, Iran. Jundishapur J Microbiol. 2015; 8(4):e15992.
29. Mukasa KJ, Herbert I, Daniel A, Sserunkuma KL, Joel B, Frederick B. Antifungal susceptibility patterns of vulvovaginal Candida species among women attending antenatal clinic at Mbarara Regional Referral Hospital, South Western Uganda. Br Microbiol Res J. 2015; 5(4):322-31.
30. Bitew A, Abebaw Y. Vulvovaginal candidiasis: species distribution of Candida and their antifungal susceptibility pattern. BMC Womens Health. 2018; 18(1):94.
31. Meyer SA, Payne RW, Yarrow D. Candida berkhout. The yeasts. Amsterdam: North-Holland Publishing Co; 1998. P. 893-1084.
32. Atkinson BJ, Lewis RE, Kontoyiannis DP. Candida lusitaniae fungemia in cancer patients: risk factors for amphotericin B failure and outcome. Med Mycol. 2008; 46(6):541-6.
33. Blinkhorn RJ, Adelstein D, Spagnuolo PJ. Emergence of a newopportunistic pathogen, Candida lusitaniae. J Clin Microbiol. 1989; 27(2):236-40.
34. Hawkins JL, Baddour LM. Candida lusitaniae infections in the era of fluconazole availability. Clin Infect Dis. 2003; 36(2):e14-8.
35. Minari A, Hachem R, Raad I. Candida lusitaniae: a cause of breakthrough fungemia in cancer patients. Clin Infect Dis. 2001; 32(2):186-90.
36. Reedy JL, Floyd AM, Heitman J. Mechanistic plasticity of sexual reproduction and meiosis in the Candida pathogenic species complex. Curr Biol. 2009; 19(11):891-9.
37. Pappagianis D, Collins MS, Hector R, Remington J. Development of resistance to amphotericin B in Candida lusitaniae infecting a human. Antimicrob Agents Chemother. 1979; 16(2):123-6.
38. Zhang J, Silao FG, Bigol UG, Bungay AA, Nicolas MG, Heitman J, et al. Calcineurin is required for pseudohyphal growth, virulence, and drug resistance in Candida lusitaniae. PLoS One. 2012; 7(8):e44192.
39. Baker JG, Nadler HL, Forgacs P, Kurtz SR. Candida lusitaniae: a new opportunistic pathogen of the urinary tract. Diagn Microbiol Infect Dis. 1984; 2(2):145-9.
40. Desnos-Ollivier M, Moquet O, Chouaki T, Guerin AM, Dromer F. Development of echinocandin resistance in Clavispora lusitaniae during caspofungin treatment. J Clin Microbiol. 2011; 49(6):2304-6.
41. Merz WG. Candida lusitaniae: frequency of recovery, colonization, infection, and amphotericin B resistance. J Clin Microbiol. 1984; 20(6):1194-5.
42. Diba K, Makhdoomi K, Nasri E, Vaezi A, Javidnia J, Gharabagh DJ, et al. Emerging Candida species isolated from renal transplant recipients: Species distribution and susceptibility profiles. Microb Pathog. 2018; 125:240-5.
43. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007; 20(1):133-63.
44. Khan Z, Ahmad S, Al-Sweih N, Khan S, Joseph L. Candida lusitaniae in Kuwait: prevalence, antifungal susceptibility and role in neonatal fungemia. PLoS One. 2019; 14(3):e0213532.
45. Florent M, Noël T, Ruprich-Robert G, Da Silva B, Fitton-Ouhabi V, Chastin C, et al. Nonsense and missense mutations in FCY2 and FCY1 genes are responsible for flucytosine resistance and flucytosine-fluconazole cross-resistance in clinical isolates of Candida lusitaniae. Antimicrob Agents Chemother. 2009; 53(7):2982-90.
46. Shen XX, Zhou X, Kominek J, Kurtzman CP, Hittinger CT, Rokas A. Reconstructing the backbone of the Saccharomycotina yeast phylogeny using genome-scale data. G3 (Bethesda). 2016; 6(12):3927-39.
47. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of clinical and laboratory standards institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012; 50(9):2846-56.
48. Lockhart SR, Pham CD, Kuykendall RJ, Bolden CB, Cleveland AA. Candida lusitaniae MICs to the echinocandins are elevated but FKS-mediated resistance is rare. Diagn Microbiol Infect Dis. 2016; 84(1):52-4.
49. Arendrup MC, Perlin DS. Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis. 2014; 27(6):484-92.
50. Espinel-Ingroff A, Pfaller MA, Bustamante B, Canton E, Fothergill A, Fuller J, et al. Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole. Antimicrob Agents Chemother. 2014; 58(4):2006-12.
51. Espinel-Ingroff A, Turnidge J. The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and moulds. Rev Iberoam Micol. 2016; 33(2):63-75.
52. Haleim M, El-Feky E, Sayed A, Kadry D, Mahmoud A, Rana A. Prevalence of Candida non albicans species associated with
vulvovaginal candidiasis in Egyptian women. Int J Adv Health Sci. 2015; 2(3):304-13.
53. Fattahi BA, Hoseinzadeh A, Jafari AA, Naghshi JM. Frequency distribution of candidal vaginitis in women referred to health centers in Yazd. J Community Health Res. 2014; 3(3):163-7.
54. Safdar A, Chaturvedi V, Cross EW, Park S, Bernard EM, Armstrong D, et al. Prospective study of Candida species in patients at a comprehensive cancer center. Antimicrob Agents Chemother. 2001; 45(7):2129-33.
55. 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.
 
Current Medical Mycology
Volume 5, Issue 4
December 2019
Pages 26-34

Files

History

  • Receive Date: 14 June 2019
  • Accept Date: 26 November 2019
  • First Publish Date: 01 December 2019

Share

How to cite

Statistics