Epidemiology and antifungal susceptibility of Candida species in a tertiary care hospital, Kolkata, India

Author

NH-Rabindranath Tagore International Institute of Cardiac Sciences 124, E. M. Bypass, Mukundapur, Kolkata–700099, West Bengal, India

Abstract

Background and Purpose: The incidence of fungal infection as well as candidemia has increased significantly, contributing to morbidity and mortality in the developed countries. The alarming increase in infections with multidrug resistant bacteria is due to overuse of a broad spectrum antimicrobials, which leads to over growth of Candida spp.; thus, enhancing its opportunity to cause the disease. A shift has been observed in the relative frequency of each Candida spp. Antifungal agents available for the treatment of systemic and invasive candidiasis are restricted to polyenes, allylamines, azoles, and the recent echinocandin class of molecules. In the past few decades, the incidence of resistance to antifungal treatment of Candida spp. has increased rapidly, which is of serious concern for healthcare professionals. Studies on prevalence of infections and antifungal susceptibility testing can help with deciding on clinical strategies to manage this problem. Herein, we aimed to identify the epidemiology of Candida spp. among blood culture isolates and to investigate the susceptibility pattern of these species to antifungal agents.
Materials and Methods: Candida spp. were isolated from blood cultures from 70 patients in a tertiary care hospital, Kolkata, India. The growth of Candida spp. on sabouraud dextrose agar was confirmed by Gram staining, where grampositive budding fungal cells were observed. The species identification as well as antifungal susceptibility testing were performed with VITEK 2 compact automated system using VITEK-2 cards for identification of yeast and yeast-like organisms (ID-YST card). Antifungal susceptibility testing was carried out with VITEK 2 fungal susceptibility card (AST-YS07) kit.
Results: Out of 70 samples, Candida albicans were isolated from 34 (48.57%) samples. The remaining 36 (51.43%) were non-albicans Candida (NAC). Out of 34 C. albicans, antifungal susceptibility was detected in 28 isolates, all of which were sensitive to fluconazole (FLC). Resistance to amphotericine B (AMP), flucytosine (5FC), voriconazole (VRC), and itraconazole (ITC) was observed in 44.12%, 52.94%, 8.82%, and 17.65% of the cases, respectively. For other Candida spp. (other than C. albicans), antifungal susceptibility was evaluated for 36 isolates, among which resistance to AMP, FLC, 5FC, VRC, and ITC was found in 30.56%, 61.11%, 33.33%, 19.44%, and 38.89% cases, respectively.
Conclusion: Species-level identification of Candida and their antifungal sensitivity testing should to be performed to achieve better clinical result and to select an appropriate and effective antifungal therapy. High resistance to antifungal agents is an alarming sign to the healthcare professionals.

Keywords


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. Richardson M, Lass-Flörl C. Changing epidemiology of systemic fungal infections. Clin Microbial Infect. 2008; 14(Suppl 4):5–24.
3. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004; 39(3):309-17.
4. Marchetti O, Bille J, Fluckiger U, Eggimann P, Ruef C, Garbino J, et al. Epidemiology of candidaemia in Swiss tertiary care hospitals: secular trends, 1991- 2000. Clin Infect Dis. 2004; 38(3):311-20.
5. Yapar N. Epidemiology and risk factors for invasive candidiasis. Ther Clin Risk Manag. 2014; 10:95-105.
6. Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national healthcare safety network at the centers for disease control and prevention, 2009–2010. Infect Control Hosp Epidemiol. 2013; 34(1):1-14.
7. Magill SS, Shields C, Sears CL, Choti M, Merz WG. Triazole cross-resistance among Candida spp.: case report, occurrence among bloodstream isolates, and implications for antifungal therapy. J Clin Microbiol. 2006; 44(2):529-35.
8. Xess I, Jain N, Hasan F, Mandal P, Banerjee U. Epidemiology of candidemia in a tertiary care centre of north India: 5-year study. Infection. 2007; 35(4):256-9.
9. Kothari A, Sagar V. Epidemiology of Candida bloodstream infections in a tertiary care institute in India. Indian J Med Microbiol. 2009; 27(2):171-2.
10. Shivaprakasha S, Radhakrishnan K, Karim PM. Candida spp. other than Candida albicans: a major cause of fungaemia in a tertiary care centre. Indian J Med Microbiol. 2007; 25(4):405-7.
11. Chakrabarti A, Chatterjee SS, Rao KL, Zameer MM, Shivaprakash MR, Singhi S, et al. Recent experience with fungaemia: change in species distribution and azole resistance. Scand J Infect Dis. 2009; 41(4):275-84.
12. Kett DH, Azoulay E, Echeverria PM, Vincent JL; Extended Prevalence of Infection in ICU Study (EPIC II) Group of Investigators. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011; 39(4):665-70.
13. Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl JP, Francais A, et al. Systemic antifungal therapy in critically ill patients without invasive fungal infection. Crit Care Med. 2012; 40(3):813-22.
14. Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, et al. Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis. 2003; 37(9):1172-7.
15. Arendrup MC, Sulim S, Holm A, Nielsen L, Nielsen SD, Knudsen JD, et al. Diagnostic issues, clinical characteristics, and outcomes for patients with fungemia. J Clin Microbiol. 2011; 49(9):3300-8.
16. Lark RL, Chenoweth C, Saint S, Zemencuk JK, Lipsky BA, Plorde JJ. Four year prospective evaluation of nosocomial bacteremia: epidemiology, microbiology, and patient outcome. Diagn Microbiol Infect Dis. 2000; 38(3):131-40.
17. Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer S, et al. Attributable mortality of nosocomial candidaemia, revisited. Clin Infect Dis. 2003; 37(9):1172-7.
18. Pfaller MA, Diekema DJ, Procop GW, Rinaldi MG. Multicenter comparison of the VITEK 2 antifungal susceptibility test with the CLSI broth microdilution reference method for testing amphotericin B, flucytosine, and voriconazole against Candida spp. J Clin Microbiol. 2007; 45(11):3522-8.
19. Falagas ME, Apostolou KE, Pappas VD. Attributable mortality of candidemia: a systematic review of matched cohort and case-control studies. Eur J Clin Microbiol Infect Dis. 2006; 25(7):419-25.
20. Fidel PL Jr, Vazquez JA, Sobel JD. Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Re. 1999; 12(1):80-96.
21. Pappas PG, Rex JH, Sobel JD, Filler SG, Dismukes WE, Walsh TJ, et al. Guidelines for treatment of candidiasis. Clin Infect Dis. 2004; 38(2):161–89.
22. Fadda ME, Podda GS, Pisano MB, Deplano M, Cosentino S. Prevalence of Candida species in different hospital wards and their susceptibility to antifungal agents: results of a three year survey. J Prev Med Hyg. 2008, 49(2):69-74.
23. Cannon RD, Lamping E, Holmes AR, Niimi K, Baret PV, Keniya MV, et al. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev. 2009; 22(2):291-321.
24. White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev. 1998; 11(2):382-402.
25. Davis SL, Vazquez JA, McKinnon PS. Epidemiology, risk factors, and outcomes of Candida albicans versus non-albicans candidemia in nonneutropenic patients. Ann Pharmacother. 2007; 41(4):568-73.
26. Skrodeniene E, Dambrauskiene A, Vitkauskiene A. Susceptibility of yeast to antifungal agents in Kaunas University of Medicina Hospital. Medicina. 2006; 42(4):294-9.
27. Kothavade RJ, Kura MM, Yaland AG, Panthaki MH. Candida tropicalis: its prevalence, pathogenicity and increasing to fluconazole. J Med Microbiol. 2010; 59(Pt 8):873-80.
28. Rex JH, Pfaller MA, Walsh TJ, Chaturvedi V, Espinel-Ingroff A, Ghannoum M, et al. Antifungal susceptibility testing: practical aspects and current challenges. Clin Microbiol Rev. 2001; 14(4):643-58.
29. Murray MP, Zinchuk R, Larone DH. CHROMagar Candida as the sole primary medium for isolation of yeasts and as a source medium for the rapidassimilation- of-trehalose test. J Clin Microbiol. 2005; 43(3):1210-2.
30. Baillie GS, Douglas LJ. Iron-limited biofilms of Candida albicans and their susceptibility to amphotericin B. Antimicrob Agents Chemother. 1998; 42(8):2146-9.
31. Clinical and Laboratory Standards Institute (CLSI). Method for antifungal disk diffusion susceptibility testing of Yeasts. Approved guideline. 2nd ed, M44-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
32. Colombo AL, Guimarães T. Epidemiologia das infecções hematogênicas por Candida spp. Rev Soc Bras Med Trop. 2003; 36:599-607.
33. Kumar CP, Sundarajan T, Menon T, Venkatadesikalu M. Candidosis in children with onco-hematological studies in Chennai, South India. Jpn J Infect Dis. 2005; 58(4):218-21.
34. Verma AK, Prasad KN, Singh M, Dixit AK, Ayyagari A. Candidaemia in patients of a tertiary health care hospital from north India. Indian J Med Res. 2003; 117:122-8.
35. Sahni V, Agarwal SK, Singh NP, Anuradha S, Sikdar S, Wadhwa A, et al. Candidemia-an underrecognized nosocomial infection in Indian hospitals. J Assoc Physicians India. 2005; 53:607-11.
36. Furnaleto MC, Rota JF, Quesada RM, Furnaleto- Maia L, Rodrigues R, Oda S, et al. Species distribution and in vitro fluconazole susceptibility of clinical Candida isolates in a Brazilian tertiarycare hospital over a 3-year period. Rev Soc Bras Med Trop. 2011; 44(5):595-9.
37. Chang MR, Correia FP, Costa LC, Xavier PC, Palhares DB, Taira DL, et al. Candida bloodstream infection: data from a teaching hospital in Mato Grosso do Sul, Brazil. Rev Inst Med Trop Sao Paulo. 2008; 50(5):265-8.
38. Akeme Yamamoto AC, de Paula CR, Dias LB, Tadano T, Martins ER, Amadio JV, et al. Epidemiological and clinical characteristics of nosocomial candidiasis in university hospitals in Cuiabá--Mato Grosso, Brazil. Rev Iberoam Micol. 2012; 29(3):164-8.
39. Hajjeh RA, Sofair AN, Harrison LH, Lyon GM, Arthington-Skaggs BA, Mirza SA, et al. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol. 2004; 42(4):1519-27.
40. Pfaller MA, Messer SA, Hollis RJ, Jones RN, Doern GV, Brandt ME, et al. Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis. 1999; 33(4):217-22.
41. Trick WE, Fridkin SK, Edwards JR, Hajjeh RA, Gaynes RP. Secular trends of hospital-acquired candidemia among intensive care unit patients in the United States during 1989-1999. Clin Infect Dis. 2002; 35(5):627-30.
42. Pfaller MA, Diekema DJ. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev. 2007; 20(1):133-63.
43. 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.
44. Chakrabarti A, Mohan B, Shrivastava SK, Marak RS, Ghosh A, Ray P. Change in distribution and antifungal susceptibility of Candida species isolated from candidaemia cases in a tertiary care centre during 1996-2000. Indian J Med Res. 2002; 116:5-12.
45. Edmond MB, Wallace SE, McClish DK, Pfaller MA, Jones RN, Wenzel RP. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis. 1999; 29(2):239-44.
46. Tortorano AM, Peman J, Bernhardt H, Klingspor L, Kibbler CC, Faure O, et al. Epidemiology of candidaemia in Europe: results of 28-month European Confederation of Medical Mycology (ECMM) hospital-based surveillance study. Eur J Clin Microbiol Infect Dis. 2004; 23(4):317-22.
47. Colombo AL, Nucci M, Park BJ, Nouér SA, Arthington-Skagg B, da Matta DA, et al. Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers. J Clin Microbiol. 2006; 44(8):2816-23.
48. Singh RI, Xess I, Mathur P, Behera B, Gupta B, Misra MC. Epidemiology of candidemia in critically ill trauma patients: experiences of a level I trauma center in North India. J Med Microbiol. 2011; 60(Pt 3):342–8.
49. Rani R, Mohapatra NP, Mehta G, Randhawa VS. Changing trends of Candida species in neonatal septicemia in a tertiary north Indian hospital. Indian J Med Microbiol. 2002; 20(1):42-4.
50. Levy I, Rubin LG, Vasishtha S, Tucci V, Sood SK. Emergence of Candida parapsilosis as the predominant species causing candidemia in children. Clin Infect Dis. 1998; 26(5):1086-8.
51. Saha R, Das Das S, Kumar A, Kaur IR. Pattern of Candida isolates in hospitalized children. Indian J Pediatr. 2008; 75(8):858-60.
52. 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.
53. Cuenca-Estrella M, Gomez-Lopez A, Alastruey- Izquierdo A, Bernal-Martinez L, Cuesta I, Buitrago MJ, et al. Comparison of the Vitek 2 antifungal susceptibility system with the Clinical and Laboratory Standards Institute (CLSI) and European Committeeon Antimicrobial Susceptibility Testing (EUCAST) broth microdilution reference methods and with the Sensititre Yeast One and Etest techniques for in vitro detection of antifungal resistance in yeast isolates. J Clin Microbiol. 2010; 48(5):1782-6.
54. Rajkumari N, Mathur P, Xess I, Misra MC. Distribution of different yeasts isolates among trauma patients and comparison of accuracy in identification of yeasts by automated method versus conventional methods for better use in low resource countries. Indian J Med Microbiol. 2014; 32(4):391-7.
55. Pappas PG, Kauffman CA, Andens D, Benjamin DK Jr, Calandra TF, Edwards JE, et al. Clinical practice guidelines for the management of candidiasis: 2009 update by infectious diseases society of America. Clin Infect Dis. 2009; 48(5):503-35.
56. Adhikary R, Joshi S. Species distribution and antifungal susceptibility of Candidaemia at a multi super-specialty center in Southern India. Indian J Med Microbiol. 2011; 29(3):309-11.