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Indian Journal of Medical Microbiology, Vol. 29, No. 3, July-September, 2011, pp. 309-311 Brief Communication Species distribution and anti-fungal susceptibility of Candidaemia at a multi super-specialty center in Southern India R Adhikary, S Joshi Department of Microbiology, Manipal Hospital, HAL Airport Road, Bangalore 560 017, India Date of Submission: 09-Jun-2011 PMID: 21860117 DOI: 10.4103/0255-0857.83920 Abstract Candidaemia is one of the leading causes of nosocomial bloodstream infections. There is a rise in the incidence of non-albicans candidaemia and emergence of anti-fungal resistance. We performed a retrospective laboratory-based study over a period of 2 years (January 2009 to December 2010) at our quaternary care multi super-specialty hospital in Southern India. There had been 68 Candida isolates detected from the bloodstream of 55 patients during the study period. Overall, 74% of cases were due to non-albicans Candida. C. tropicalis was most commonly isolated (39.7%), followed by C. albicans (26.4%). All Candida isolates remain susceptible to voriconazole, whereas highest degree of resistance was observed for fluconazole.Keywords: Candidaemia, candida species, candida albicans, non-albicans candida Introduction There has been an increase in the incidence of candidaemia over the last two decades in different parts of the world and in various clinical settings. [1] It is reported as the fourth leading cause of nosocomial bloodstream infection in the USA. [1],[2] There are also reports suggesting an increase in candidaemia in Europe, Australia and India. [3],[4] Moreover, there has been a shift in the relative frequency of each Candida spp. isolated from blood. There are published data from various centres regarding the incidence and relative frequency of Candida spp. [1] The increase in candidaemia is associated with high mortality. Growing population of immunocompromised patients and advances in medical and surgical managements has contributed an increase in candidaemia. [3],[5] Other associated risk factors include exposure to broad spectrum anti-microbial agents, mucosal colonization by Candida spp., indwelling vascular catheters and premature infants. [6],[7] The mortality attributed to candidaemia ranged from 5% to 71% in various reviewed studies. [8] The aim of this study was to investigate the distribution pattern of Candida spp. from blood cultures and evaluate its anti-fungal susceptibility pattern. Materials and Methods A retrospective analysis of data was done from January 2009 to December 2010 in a quaternary care multi super-specialty center in Southern India from laboratory information system and case files. Blood samples were collected aseptically in BactAlert culture bottles and incubated at 37 0 C for 10 days. When BactAlert indicated positive, bottles were unloaded, preliminary Gram stain and subcultures were made on 5% sheep blood agar. These were further identified into species level by (a) germ tube production, (b) growth on corn meal agar, (c) pigmentation on chromogenic medium (CHROM agar Candida), and (d) carbohydrate assimilation tests using the VITEK 2 compact system (bioMerieux). Adequate quality control measures were undertaken with reference strains C. krusei ATCC 6258 and C. parapsilosis ATCC 22019. A case of candidaemia was defined as the isolation of at least one positive blood culture containing Candida species with supportive clinical correlation. Anti-fungal susceptibility was also done against fluconazole, flucytosine, voriconazole and amphotericin B in VITEK 2 compact system. Following interpretive susceptible criteria for anti-fungal were used. For fluconazole, breakpoints were as follows: susceptible(S), MIC ≤8 μg/ml; susceptible-dose dependent (SDD), MIC = 16 to 32 μg/ml; resistant(R), MIC ≥64 μg/ml. For flucytosine, isolates showing MIC′s ≤4 μg/ml were considered as susceptible, 8--16 μg/ml as intermediate and ≥32 μg/ml as resistant. For voriconazole, breakpoints followed were: susceptible ≤1.0 μg/ml, 2.0 μg/ml as dose-dependent and ≥4 μg/ml as resistant. For amphotericin B, isolates showing a MIC of ≤1.0 μg/ml were taken as susceptible and those with MIC >1 μg/ml were considered as resistant. [9],[10] Results There were 68 different episodes of candidemia detected in 55 patients during the two-year study period [Table - 1]. Ten patients had more than one episode of candidaemia. Among them, 60 isolates were available for the susceptibilities of anti-fungal agents. Most of the episodes have been caused by non-albicans Candida (74%). C. tropicalis accounted for 39.7% of the isolates, followed by C. albicans (26.4%), C. lipolytica (5.8%), C. famata (4.4%), C. parapsilosis (4.4%), C. pelliculosa (4.4%), C. guilliermondii (2.9%), C. lusitaniae (1.4%), C. sphaeria (1.4%) and others that could not be speciated Candida spp. (8.8%). Mortality rate in our study was 37%. We identified 3 infants, 17 children and 35 adults with Candida blood stream infection. Out of 55 patients, 27 (49%) were from the ICU. In relation to predisposing factors, 19% of candidaemia occurred in patients with malignancies receiving chemotherapy, 42% had undergone major surgical procedures and 65% had received broad-spectrum antibiotics. The susceptibility profile of all Candida isolates showed 100% sensitivity to voriconazole, 92% to amphotericin B, 90% to flucytosine and 75% to fluconazole. Dose-dependent susceptibility to fluconazole was observed in 25% of the isolates. C. tropicalis, the most commonly isolated species was 100% sensitive to amphotericin B and voriconazole, 95% sensitive to flucytosine and 81% sensitive to fluconazole. Discussion Although significant geographic variation is observed among cases of candidaemia in different parts of the world, there appears to follow a specific pattern. In our study, non-albicans Candida bloodstream infections were more common than C. albicans bloodstream infections. This finding is consistent with other studies where non-albicans Candida spp predominate in Asia, South Europe, South America and also in the subcontinent of India. [1],[4] In our study among the non-albicans Candida, C. tropicalis was isolated more frequently. This is in line with previous data from India, which showed C. tropicalis as the most commonly isolated agent from blood. [4],[5],[11],[12] This finding is also in consistent with review article where highest proportion of C. tropicalis was isolated in Eastern Asia and Argentina. [1] In a study conducted in the same region as ours, there was a significant difference in distribution of Candida species. [13] The most common isolates in their study were C. albicans (47%) followed by C. tropicalis (23%). We have not isolated C. krusei in our study which is generally low in all settings and geographic regions. [1] The decrease in susceptibility of Candida isolates to fluconazole (75%) is a matter of concern although voriconazole, amphotericin B and flucytosine continue to show good efficacy. Western data have shown that Candida species are reliably susceptible to polyenes, flucytosine, azoles and echinocandins. [7] But a study from India has shown a very high resistance of 56% to voriconazole and 36% to fluconazole for all candidal isolates although the amphotericin B susceptibility (92%) is same as in our study. [12] With various types of antifungals available in the market, it has become necessary to perform anti-fungal susceptibility testing and reporting for effective therapeutic outcome. Evaluation of newer anti-fungal agents is needed. The mortality rate in our study is much less (37%) than the study conducted in northern part of India (60%). [12] Our rate falls in the range of 10%-49% as mentioned in the review article. [7] Our study is limited by a single institution′s experience, retrospective design, lack of information about the cost associated with Candida infection and virulence among Candida species in different age groups. Additionally, the small numbers of isolates of C. guilliermondii, C. lusitaniae and C. sphaeria has limited our ability to evaluate the relative significance of these specific non-albicans species. Further studies with richer clinical data and larger samples will be required to more fully evaluate cost associated with albicans and non-albicans Candida species. The changing epidemiology of candidaemia, therefore, highlights the need for close monitoring of Candida species distribution and susceptibility in order to optimise therapy and outcome. We should also develop guidelines for empiric therapy based on the epidemiology of India. References
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