ISSN: 0973-7510
E-ISSN: 2581-690X
Candidemia ranks the 4th most prevalence cause of bloodstream infections and stands out as the primary cause of invasive fungal infections among hospitalized patients. Its incidence varies globally from 0.33 to 6.51 episodes per 1000 admissions, representing a major public health burden due to its increasing incidence and high mortality rates. The present research work has been conducted to identify the distribution of Candida species among septicemic patients and to determine the patterns of antifungal susceptibility of Candida species isolates from them in a tertiary care center in South India. Among the 88 Candida isolates, 13 (14.8%) were speciated and identified as C. albicans and 75 (85.2%) were Candida non-albicans. Of them, C. tropicalis (42%) ranks more prevalent. The distribution of virulence factors among 88 Candida isolates revealed that 49 isolates (55.7%) exhibited phospholipase activity, hemolysin production was detected in 68.2% of isolates, biofilm production was demonstrated in 73.9% isolates and coagulase activity was observed in 46.7% isolates. In the present study, Candida species were most sensitive to Amphotericin B (94.3%), which is followed by Caspofungin (93.2%), Voriconazole (92%), Micafungin (90.9%), and the least was observed with Flucytosine (78.4%) and Fluconazole (71.5%). Thus, in order to improve treatment responses, the insights acquired from this research will aid in clinical management and the development of antifungal stewardship recommendations.
Candidemia, Candida Species, Virulence Factors, Antifungal Agents, Antifungal Stewardship Guidelines
Candidemia remains the most prevalent invasive nosocomial fungal infection worldwide. Its incidence varies globally from 0.33 to 6.51 episodes per 1000 admissions, representing a major public health burden due to its increasing incidence and high mortality rates.1 Frequently administering antibiotics, employing central venous catheters, as well as other invasive medical devices, along with conditions including stays in the intensive care units (ICUs) and could make patients at risk of obtaining a Candida infection.2 Global reports have indicated rising incidence of candidemia brought on by Candida krusei, Candida tropicalis, Candida glabrata, Candida parapsilosis, despite the fact that Candida albicans remains the most prevalent species being responsible for more than 50% of cases in some series.3
Candida spp. are commensal organisms present in the gut and skin of 50-70% of healthy individuals in low numbers due to competition within the microbiome.4 Moreover, Candida translocation from the gut into the bloodstream can be facilitated by increased permeability of the gut epithelia (for example, due to mucositis in onco-haematological patients or patients with inflammatory bowel disease) or breaches in the intestinal barrier following abdominal surgery, all of which significantly increase the risk of candidaemia.4-6
The evolution of Candida from a commensal organism to a formidable pathogen is facilitated by a number of host variables as well as the virulence of the infecting species. Patients who are critically sick yet are immunocompetent can also frequently have candidiasis as Candida formerly thought to play a passive part in the overall process of infection initiation and development.7 Candida has a variety of virulence factors that determine its capacity for penetration of host tissues. The virulence factors of Candida are multifaceted and include the formation of biofilms as well as the release of extracellular hydrolytic enzymes that damage tissue, such as phospholipases, hemolysin, and proteinases. The capacity for it to adhere to medical equipment and host tissues, as well as the development of pseudohyphae makes it pathogenic.8 Comprehension and evaluation of these virulence characteristics in newly developing drug-resistant yeast infections will aid in the creation of innovative target-specific medications in the future.9
A growing number of strains of Candida species are emerging that are resistant to azoles, mostly in the form of prophylaxis and to a lesser extent with echinocandins have been associated with the occurrence of breakthrough infections with resistant Candida species.10 This is an extremely disturbing trend, possibly associated with increased use of azoles as prophylaxis, especially in surgical units and intensive care units.11 Therefore, there is a need for continuous surveillance to monitor trends in incidence, species distribution and antifungal drug susceptibility profiles of Candida BSI.12 Hence, the present research work has been conducted to identify the distribution of Candida species among septicemic patients and to determine the patterns of antifungal susceptibility of Candida species isolates from them in a tertiary care center in South India.
The present cross-sectional study has been undertaken at a tertiary care centre, and from the Institute Ethical Committee for Human Studies, ethical permission (2896/IEC/2021) was acquired. A sum of 2114 blood samples from suspected septicaemia cases was collected in blood culture bottles throughout ICUs and various wards between August 2021 and December 2022. In order to detect gram-positive budding yeasts, bottles displaying positive signals were subjected to direct gram staining technique and cultured onto Sabouraud dextrose agar (HiMedia, India) incubated for a duration of 24 to 48 hours at 25°C and 37°C. Candida colonies were detected and speciated in VITEK 2 Compact (Biomerieux) using VITEK® 2 PC LIS-compatible software with Yeast Identification 21343 after being confirmed by Gram staining and the germ tube test and Yeast AST YS08 420739 cards, was used for determination of antifungal susceptibility test (AFST) patterns were carried out. The AFST panel comprised the following drugs: Flucytosine, Micafungin, Amphotericin B, Voriconazole, Fluconazole, and Caspofungin with the recommendations established by the Clinical and Laboratory Standards Institute (CLSI) guidelines.
Analysis of MIC results
To compute the percentage of essential agreement (A) between the MIC values and the species identification, the repeatability and accuracy of the data produced with the VITEK 2 system were compared to the reference methodologies. The critical agreement was determined by comparing differences in MIC endpoints of more than ±2 log2 dilutions, following Pfaller et al.13
Comparisons were made between the reference broth microdilution (BMD) panels read at 24 and 48 hours and the MIC values from the VITEK 2 yeast susceptibility test. Similar to other research, low off-scale MIC results were not altered while high off-scale MIC values were translated to the next highest concentration.14-16 The essential agreement (EA) was determined by comparing the MIC endpoints of more than two dilutions (two wells) in disagreement. The CLSI guidelines (M27-A2 4th Edition) were utilised to interpret the MIC breakpoints for Flucytosine, Micafungin, Amphotericin B, Voriconazole, Fluconazole, and Caspofungin. The MICs produced by VITEK 2 and the reference BMD were then compared to calculate the percentage of categorical agreement (CA).17 When the VITEK 2 MIC showed S and the reference MIC indicated R, very substantial errors (VME) were found. When the isolate was categorised as R by VITEK 2 and S by the reference technique, major errors (ME) were found. When the findings of one test technique were S or R and the other was SDD, minor flaws were identified. The C. krusei MIC data were utilised as-is (in micrograms per millilitre) to evaluate EA; however, while calculating CA, the CLSI forced the results into the R category.17
Assessments of virulence factors
Phospholipase Production
The standard test strain was then inoculated onto agar enriched with egg yolk using a 5 µL aseptically produced inoculum. Following a 48-hour incubation period at 37°C, the Petri plates were given time to dry at room temperature. The colony was encircled with precipitation zone existence was then studied and this showed that the phospholipase enzyme was expressed. C. albicans ATCC 10231 served as the positive control. The phospholipase index (Pz) is obtained by dividing the colony diameter by the precipitation zone ratio. Positive activity is shown by Pz < 1, whereas no phospholipase synthesis is shown by Pz > 1. For every isolate, the test was conducted three times in duplicate to reduce experimental error.18
Haemolysin production
It was demonstrated on SDA supplemented with sheep blood and gentamicin and inoculated with 10 µL of prepared inoculum obtained from the isolates. Following this, C. albicans ATCC 90028 was used as a control and 48 hours of 37°C incubation was required for the aforementioned medium-containing petri plates. Hemolytic activity (Hz) is determined as the ratio of the colony diameter to the visible hemolysis zone (in millimetres).19
Biofilm production – crystal violet assay
The Crystal Violet test technique described by Kuhn et al. was used to measure the production of biofilms.20 The microtiter plate was added with 0.1% aqueous solution of crystal violet (120 µL) for 15 minutes. Sterilised distilled water was used to wash the wells four times. A 15-minute incubation period at room temperature was then followed by the addition of 125 µL of 95% methanol to each well to de-stain the experiment. Then, using an Enzyme-Linked Immunosorbent Assay reader, the de-stained wells were examined using spectroscopy at 570 nm. Reference strains of C. albicans (ATCC 90028) served as a positive control strain, while C. glabrata (ATCC 90030) was used as a negative control strain.21,22
The cut-off optical density (ODc) was defined as three standard deviations above the mean OD of the negative control, and the strains were classified as follows:
OD Values |
Biofilm Formation |
ODc
| strong biofilm producer |
2 × ODc
| moderate biofilm producer |
ODc
| weak biofilm producer |
OD ≤ ODc |
no biofilm producer |
Coagulase activity
Coagulase production was measured in accordance with the procedure devised by Yigit et al.23 After adding 500 µL of rabbit plasma as a supplement, 0.1 mL of an overnight inoculum was aseptically added to a tube. The tubes were examined after being incubated at 35°C for 2, 4, 6, and 24 hours. When a coagulase test is positive, clot formation will appear.
Data analysis
SPSS software (version 22, IBM Inc. Chicago) was used for analysis following data collection. P-values <0.05 were significant.
Distribution and prevalence of Candida species
In the present study, out of 88 Candida isolates following identification and speciation, 13 (14.8%) were C. albicans and 75 (85.2%) were identified as Candida non-albicans (CNA). Among CNA isolates, C. tropicalis was the most prevalent species, constituting 37 isolates (42%) followed by C. parapsilosis with 21 isolates (23.9%), 13 (14.8%) C. albicans, 6 (6.8%) C. glabrata, 5 (5.6%) C. krusei, and both C. lipolytica and C. auris, each with 3 isolates (3.4%), respectively (Table 1).
Table (1):
Species-wise distribution (n=88)
Candida species |
Total number of isolates |
Percentage (%) |
---|---|---|
C. albicans |
13 |
14.8% |
C. parapsilosis |
21 |
23.9% |
C. tropicalis |
37 |
42% |
C. glabrata |
6 |
6.8% |
C. krusei |
5 |
5.6% |
C. auris |
3 |
3.4% |
C. lipolytica |
3 |
3.4% |
Total |
88 |
100% |
Virulence activity among Candida isolates
The distribution of phospholipase activity among 88 Candida isolates revealed that 49 isolates (55.7%) exhibited phospholipase activity. Phospholipase activity was better in C. albicans in comparison with CNA isolates (p < 0.05*) as it showed statistically significant results. Notably, C. tropicalis had the highest prevalence of phospholipase activity, with 19 isolates (38.8%), followed by C. albicans with 11 isolates (22.4%), C. parapsilosis with 9 isolates (18.4%), C. glabrata with 5 isolates (10.2%), C. krusei with 2 isolates (4.1%), C. auris with 1 isolate (2%), and C. lipolytica with 2 isolates (4.1%) ( Table 2 and Table 3).
Table (2):
Comparison of various virulence factors expressed by Candida albicans and Candida non-albicans isolated from candidemia patients
Virulence activity | Interpretation | C. albicans (n-13) |
Candida non albicans (n-75) |
p value |
---|---|---|---|---|
Phospholipase Activity (n-49) | Positive | 11 | 38 | 0.0328* |
Negative | 2 | 37 | ||
Hemolysin production (n-60) | Positive | 6 | 54 | 0.1037 |
Negative | 7 | 21 | ||
Biofilm production (n-65) | Positive | 9 | 56 | 0.7359 |
Negative | 4 | 19 | ||
Coagulase Activity (n-42) | Positive | 13 | 29 | 0.0000* |
Negative | 0 | 46 |
The result is significant at p < .05.
Table (3):
Distribution of Virulence activity among Candida isolates (n=88)
Candida species |
Phospholipase activity (%) |
Hemolysin production (%) |
Biofilm production (n%) |
Coagulase activity (%) |
---|---|---|---|---|
C. albicans (n=13) |
11 (22.4%) |
6 (10%) |
9 (12.9%) |
13 (31%) |
C. tropicalis (n=37) |
19 (38.8%) |
25 (41.7%) |
31 (44.3%) |
12 (28.6%) |
C. parapsilosis (n=21) |
9 (18.4%) |
20 (33.3%) |
18 (25.7%) |
10 (23.8%) |
C. glabrata (n=6) |
5 (10.2%) |
4 (6.6%) |
4 (5.6%) |
4 (9.4%) |
C. krusei (n=5) |
2 (4.1%) |
3(5%) |
3 (4.3%) |
2 (4.8%) |
C. auris (n=3) |
1 (2%) |
1 (1.7%) |
0 (0%) |
0 (0%) |
C. lipolytica (n=3) |
2 (4.1%) |
1 (1.7%) |
0 (0%) |
1 (2.4%) |
Total (n=88) |
49 (55.7%) |
60 (68.2%) |
65 (73.9%) |
42 (46.6%) |
Moreover, hemolysin production was detected in 60 isolates (68.2%), predominantly in C. tropicalis with 25 cases (41.7%), followed by C. parapsilosis with 20 cases (33.3%), C. albicans with 6 cases (10%), C. glabrata with 4 cases (6.6%), C. krusei with 3 cases (5%), C. auris with 1 case (1.7%), and C. lipolytica with 1 case (1.7%). Whereas there was no statistically relevant difference was observed between hemolysin production of C. albicans and CNA isolates (p > 0.05) (Table 2 and Table 3).
Regarding coagulase activity, it was observed in 42 isolates (46.7%), with C. albicans exhibiting the highest incidence among 13 isolates (31%), followed by C. tropicalis with 12 isolates (28.6%), C. parapsilosis with 10 isolates (23.8%), C. glabrata with 4 isolates (9.4%), C. krusei with 2 isolates (4.8%), and C. lipolytica with 1 isolate (2.4%). There was statistically significant difference was found between coagulase production of C. albicans and CNA isolates (p < 0.05*) ( Table 2 and Table 3).
Furthermore, biofilm production was demonstrated by 70 isolates (73.9%) through crystal violet assay, with C. tropicalis predominantly displaying biofilm production in 31 isolates (44.3%), followed by C. parapsilosis with 18 isolates (25.7%), C. albicans with 9 isolates (12.9%), C. glabrata with 4 isolates (5.6%), and C. krusei with 3 isolates (4.3%). There was statistically significant difference was found between biofilm production of C. albicans and CNA isolates (p > 0.05) ( Table 2 and Table 3).
Antifungal susceptibility pattern of Candida isolates by VITEK 2
The 88 Candida isolates underwent Antifungal Drug Susceptibility tests using VITEK 2 against Flucytosine, Micafungin, Amphotericin B (100 U), Voriconazole, Fluconazole, and Caspofungin. Based on their MIC values, the isolates were categorized as Sensitive (S) and Resistant (R) to each antifungal drug. In the present study, the most sensitive antifungal agent was Amphotericin B (94.3%), which is followed by Caspofungin (93.2%), Voriconazole (92%), Micafungin (90.9%), and the least was observed with Flucytosine (78.4%) and Fluconazole (71.5%) as shown in Table 4.
Table (4):
Distribution of Antifungal susceptibility and minimum inhibitory concentration (MIC) range of isolated Candida species from VITEK 2 (n=88)
Candida species | Fluconazole (0.5 to 64 µg/ml) | Voriconazole (0.125 to 8 µg/ml) | Amphotericin B (0.5 to 8 µg/ml) | Caspofungin (0.125 to 8 µg/ml) | Micafungin (0.06 to 8 µg/ml) | Flucytosin (1 to 64 µg/ml) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
S | R | S | R | S | R | S | R | S | R | S | R | ||
C. albicans (n=13) | 10 (77%) | 3 (23%) | 13 (100%) | 0 (0%) | 13 (100%) | 0 (0%) | 13 (100%) | 0 (0%) | 12 (92.3%) | 1 (7.7%) | 12 (92.3%) | 1 (7.7%) | |
C. tropicalis (n=37) | 28 (75.7%) | 9 (24.3%) | 36 (97.3%) | 1 (2.7%) | 34 (91.9%) | 3 (8.1%) | 34 (91.8%) | 3 (8.1%) | 35 (86.5%) | 2 (13.5%) | 33 (89.2%) | 4 (10.8%) | |
C. parapsilosis (n=21) | 15 (71.4%) | 6 (28.6%) | 18 (85.7%) | 3 (14.3%) | 19 (90.5%) | 2 (9.5%) | 20 (85.7%) | 1
(14.3%) |
16 (76.2%) | 5 (23.8%) | 15 (71.5%) | 6 (28.5%) | |
C. glabrata (n=6) | 1 (16.7%) | 5 (83.9%) | 4 (66.7%) | 2 (33.3%) | 6 (100%) | 0 (0%) | 5 (83.3%) | 1 (16.7%) | 6 (100%) | 0 (0%) | 2 (33.3%) | 4 (66.7%) | |
C. krusei (n=5) | 0 (0%) | 5 (100%) | 4 (80%) | 1 (20%) | 5 (100%) | 0 (0%) | 4 (80%) | 1 (20%) | 5 (100%) | 0 (0%) | 1 (20%) | 4 (80%) | |
C. auris (n=3) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | |
C. lipolytica (n=3) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | 3 (100%) | 0 (0%) | |
Total (n=88) | 63 (71.5%) | 26 (29.5%) | 81 (92%) | 7 (8%) | 83 (94.3%) | 5 (5.7%) | 82 (93.2%) | 6 (6.8%) | 80 (90.9%) | 8 (9.1%) | 69 (78.4%) | 19 (21.6%) |
Out of 88 Candida isolates, 13 C. albicans were 100% sensitive to Voriconazole, Amphotericin B, and Caspofungin. Whereas, among them, 3 (23%) isolates showed resistance to fluconazole and 1 (7.7%) isolate was resistant to each of Micafungin and flucytosine. Among CNA, C. auris and C. lipolytica demonstrated 100% sensitivity to all the antifungals used. The highest resistance was observed against Fluconazole (29.5%). Nonetheless, due to their intrinsic resistence, C. krusei (100%) displayed total resistance to fluconazole. In turn, it has been noted in this investigation that CNA isolates exhibited greater resistance to antifungal drugs in comparison to C. albicans (Table 4).
In the current study, C. tropicalis (n=37; 42%) emerged to be the species with the greatest prevalence detected out of the total. The results of the current investigation were consistent with those of studies by Tak et al., Rajni et al., and Selvan et al., which indicated that C. tropicalis isolated species frequently in India, accounting for 39%, 38%, and 47.16% of the total.24-26 Additionally, C. tropicalis (27.7%) was reported to be the major species causing candidemia in Chile by Ajenjo et al.27 Conversely, the research findings by Tan et al. demonstrated that the most common isolate from individuals with candidemia was C. albicans (41.3%).28 However, over the past several decades, there was a steady rise in the isolation of CNA isolates from candidemia patients. CNAs are known to be associated with greater death rates because of their enhanced virulence and decreased sensitivity to antifungal medications.28
A notable finding in the current research is the identification of C. auris in 3 isolates (3.4%) among all cases of candidemia. The findings did not agree with the results of another recent study in India by Rajni et al. and Shastri et al. In the previous research, the prevalence of C. auris accounted for about 11% and 39.9% of candidemia cases, respectively.25,29 The development of this C. auris is extremely worrying since it causes serious infections in critically sick patients and spreads quickly across the hospital due to its resistance to numerous antifungals. The inability of the widely used phenotypic commercial method to correctly detect this fungus is another significant problem. When creating a treatment strategy, a precise identification of this yeast is crucial. We speculate that the low number of studies from India reporting C. auris may be due to misidentification by traditional methods. However, healthcare professionals must be aware of this multidrug-resistant fungus and ready for any possible breakout.30
A wide range of virulence factors, the transition from yeast to hyphae, involving biofilm formation, the release of tissue-damaging hydrolytic enzymes like phospholipases, proteases and hemolysins), adherence and invasion to target cell surfaces, and immune cell evasion, all contribute to Candida’s pathogenicity.31,32 Candida species secrete phospholipases that are involved in tissue invasion, and they hydrolyze phospholipids as substrates, rupturing host cell membranes in the process.31,33 Out of the 88 Candida isolates found in this study, 49 (55.7%) showed evidence of phospholipase activity. These results were compared with the findings of a study by Sachin C et al. (60.9%), with C. tropicalis having the highest prevalence of phospholipase activity (38.8%).34 These results are comparable to those of the study conducted by Sharma et al., which found that in 30% of patients had C. tropicalis displaying significant phospholipase activity.35 On the other hand, according to a prior work by Saiprom et al. all 26.3% of the C. albicans isolates generated high phospholipase activity, but none of the NAC spp. showed phospholipase activity.31
The ability of Candida to produce hemolysin, which lyses red blood cells to extract iron from haemoglobin and promotes hyphal penetration and yeast spread in the host, is a critical component of the virulence of Candida.31,36 Hemolysin production was found in 60 (68.2%) Candida isolates in our investigation; the current study’s findings were consistent with those of Galan-Ladero et al. study, which revealed that around 77.2% of Candida isolates had hemolysin production.37 In this investigation, hemolysin production was predominantly reported in 25 (41.7%) of C. tropicalis. The results of the current investigation were consistent with those of Selvan et al. study, which indicated that 61.1% of C. tropicalis was a hemolysin producer and the proportion of hemolysin producers was significantly lower than that of our study.26 However, the findings of the study by Nouraei
et al. demonstrated that 100% of Candida albicans generated hemolysin activity.38 Additionally, the findings of the study by Badran et al. revealed that isolates of C. albicans (84.9%) exhibited hemolysin activity the most frequently.39
One of the most studied virulence variables linked to bloodstream infections caused by Candida is biofilm development, which has also been linked to pathogenicity in candidemia connected to catheter use.40 Furthermore, the production of biofilm makes it easier for Candida to adhere to prosthetic joints, vascular catheters, cardiac devices.41 Due to its well-known strong resistance to antifungal medications, Candida biofilm is a major factor in the infection’s fatality.40 By using the crystal violet assay, 70 isolates (73.9%) in the current investigation were able to produce biofilms, and these results were correlated with Tulasidas et al. study, which found biofilm activity in 74% of Candida isolates.42 According to our findings, C. tropicalis (44.3%) formed the majority of biofilm, which is consistent with earlier research by Sasani et al. that found C. tropicalis (47%) produced the most biofilm relative to other Candida species.43 Alternatively, C. parapsilosis (78%) demonstrated strong biofilm generation, according to findings published by Sriphannam
et al.40
Of 42 (46.6%) Candida isolates that showed coagulase activity among 88 Candida isolates, 13 (31%) were C. albicans, which demonstrated the greatest coagulase activity. These results were quite similar to those reported by Yigit et al., whose work found that coagulase activity was found in Candida albicans isolates, accounting for 50.6% of the isolates.23
Candida species has a dynamic resistance pattern that differs across different regions.44 The antibiogram pattern of 88 Candida isolates in this study indicated that the most sensitive antifungal agent was Amphotericin B (94.3%), which was consistent with the findings of studies by Siopi et al. and Giri et al. that showed 100% of the Candida isolates were Amphotericin B sensitive.45,46 The current study demonstrates that the greatest resistance was seen against fluconazole (29.5%), and these results were consistent with research studies by Giri et al. that indicated the greatest percentage of Candia isolates (30.8%) were resistant to fluconazole.46 Because fluconazole is the most commonly used antifungal medication that is empirically administered to all high-risk patients, resistance to it is increasing. This has led to the emergence of resistant strains, including C. glabrata and intrinsically fluconazole-resistant forms of C. krusei.47,48 In contrast, CNA species exhibited higher resistance to flucytosine (16.04%) and fluconazole (14.81%) in research by Gautam et al. than C. albicans.38 In line with other research findings by Bhattacharjee et al. and Gautam et al., a lower prevalence of resistance has been determined for Micafungin (8.57%), Voriconazole (8%), Caspofungin (6.8%), and Amphotericin B (1.43%). A few more isolates also showed resistance to Flucytosine (20%).44,48
In this investigation, all 13 of the C. albicans isolates showed complete sensitivity to caspofungin, amphotericin B, and voriconazole. These results coincide with the findings presented by Solomon et al., which demonstrated that all isolates were susceptible to echinocandins (caspofungin), voriconazole, and amphotericin B.49 Conversely, the results of the study by Bhattacharjee et al. revealed that all of the C. albicans isolates were 100% susceptible to fluconazole, and that resistance to flucytosine (64.3%), amphotericin B (53.6%), itraconazole (21.4%), and voriconazole (10.7%) was identified.44 Out of all the CNA isolates, C. lipolytica and C. auris showed complete sensitivity to every antifungal that was used. In contrast, C. auris was shown to have a high resistance pattern for fluconazole in research by Solomon et al., suggesting that 9 Candida isolates tested against the drug were sensitive.49
There has been a significant shift in the prevalence of Candida bloodstream infections from C. albicans to CNA species. Consequently, the sensitivity of each species to the antifungal medications now in use varies greatly, early and precise detection of Candida infection is imperative. Aside from assisting clinicians to administer the right antifungal medication in a timely manner, laboratory testing for antifungal susceptibility may also limit the empirical use of existing antifungal drugs.49
The present research concludes by emphasizing the rising prevalence of C. tropicalis as the leading cause of candidaemia while highlighting the increasing incidence of rarer Candida species such as C. auris and C. lipolytica. The emergence of various CNA species as significant pathogens underscores the critical need for routine and precise differentiation in clinical laboratories. Additionally, the alarming rise in Fluconazole resistance further accentuates the necessity for accurate species identification and antibiogram assessments in routine laboratory procedures to ensure effective patient management and treatment strategies.
ACKNOWLEDGMENTS
None.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
AUTHORS’ CONTRIBUTION
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
FUNDING
None.
DATA AVAILABILITY
All datasets generated or analyzed during this study are included in the manuscript.
ETHICS STATEMENT
The study was approved by the Institutional Ethical Committee of SRM Medical College Hospital and Research Centre (2896/IEC/2021).
- Agnelli C, Guimaraes T, Sukiennik T, et al. Prognostic Trends and Current Challenges in Candidemia: A Comparative Analysis of Two Multicenter Cohorts within the Past Decade. J Fungi. 2023;9(4):468.
Crossref - Schelenz S. Management of candidiasis in the intensive care unit. J Antimicrob Chemother. 2008;61(Suppl 1):i31-i34.
Crossref - Bac ND, Anh LT, Quang LB, et al. Prevalence of Candida bloodstream isolates from patients in two hospitals in Vietnam. Iran J Microbiol. 2019;11(2):108-113.
- Soriano A, Honore PM, Puerta-Alcalde P, et al. Invasive candidiasis: current clinical challenges and unmet needs in adult populations. J Antimicrob Chemother. 2023;78(7):1569-1585.
Crossref - Gamaletsou MN, Walsh TJ, Zaoutis T, et al. A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies. Clin Microbiol Infect. 2014;20(1):O50-57.
Crossref - Mayer FL, Wilson D, Hube B. Candida albicans pathogenicity mechanisms. Virulence. 2013;4(2):119-128.
Crossref - Deorukhkar SC, Roushani S. Virulence Traits Contributing to Pathogenicity of Candida Species. J Microbiol Exp. 5(1):00140.
Crossref - Siddiqui R, Mendiratta DK, Siddiqui AF, Rukadikar A. A study of the association between virulence factors and antifungal susceptibility profile of Candida species recovered from cases of vulvovaginal candidiasis. J Family Med Prim Care. 2023;12(1):152-159.
Crossref - Angiolella L, Rojas F, Giammarino A, Bellucci N, Giusiano G. Identification of Virulence Factors in Isolates of Candida haemulonii, Candida albicans and Clavispora lusitaniae with Low Susceptibility and Resistance to Fluconazole and Amphotericin B. Microorganisms. 2024;12(1):212.
Crossref - Gupta P, Prateek S, Chatterjee B, Kotwal A, Singh AK, Mittal G. Prevalence of Candidemia in ICU in a Tertiary Care Hospital in North India. Int J Curr Microbiol App Sci. 2015;4(6):566-575
- Kothari A, Sagar V. Epidemiology of candida bloodstream infections in a tertiary care institute in India. Indian J Med Microbiol. 2009;27(2):171-172.
Crossref - Behera SR, Panda RK, Khatua S, Majhi S, Swain M. Prevalence And Antifungal Susceptibility Profile of Candida Species Isolated from Blood Stream Infections in Neonates in a Tertiary Care Hospital. Int J Acad Med Pharm. 2023;5(6);237-242
Crossref - Pfaller MA, Diekema DJ, Procop GW, Rinaldi MG. Multicenter comparison of the VITEK 2 yeast susceptibility test with the CLSI broth microdilution reference method for testing fluconazole against Candida spp. J Clin Microbiol. 2007;45(3):796-802.
Crossref - Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. Clinical evaluation of a dried commercially prepared microdilution panel for antifungal susceptibility testing of five antifungal agents against Candida spp. and Cryptococcus neoformans. Diagn Microbiol Infect Dis. 2004;50(2):113-117.
Crossref - Pfaller MA, Espinel-Ingroff A, Jones RN. Clinical evaluation of the Sensititre Yeast One colorimetric antifungal plate for antifungal susceptibility testing of the new triazoles voriconazole, posaconazole, and ravuconazole. J Clin Microbiol. 2004;42(10):4577-4580.
Crossref - Espinel-Ingroff A, Barchiesi F, Cuenca-Estrella M, 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):3884-3889.
Crossref - M27 ED4 broth dilution antifungal susceptibility, yeasts. Clinical & Laboratory Standards Institute. https://clsi.org/standards/products/microbiology/documents/m27/. Accessed July 15, 2024.
- Samaranayake LP, Raeside JM, Macfarlane TW. Factors affecting the phospholipase activity of Candida species in vitro. Med Mycol. 1984;22(3):201-207.
Crossref - Manns JM, Mosser DM, Buckley HR. Production of a hemolytic factor by Candida albicans. Infect Immun. 1994;62(11):5154-5156.
Crossref - Kuhn DM, Chandra J, Mukherjee PK, Ghannoum MA. Comparison of biofilms formed by Candida albicans and Candida parapsilosis on bioprosthetic surfaces. Infect Immun. 2002;70(2):878-888.
Crossref - Li X, Yan Z, Xu J. Quantitative variation of biofilms among strains in natural populations of Candida albicans. Microbiology. 2003;149(Pt 2):353-362.
Crossref - Kadkhoda H, Ghalavand Z, Nikmanesh B, et al. Characterization of biofilm formation and virulence factors of Staphylococcus aureus isolates from paediatric patients in Tehran, Iran. Iran J Basic Med Sci. 2020;23(5):691-698.
Crossref - Yigit N, Aktas E, Dagistan S, Ayyildiz A. Investigating Biofilm Production, Coagulase and Hemolytic Activity in Candida Species Isolated from Denture Stomatitis Patients. Eurasian J Med. 2011;43(1):27-32.
Crossref - Tak V, Mathur P, Varghese P, Gunjiyal J, Xess I, Misra MC. The epidemiological profile of candidemia at an Indian trauma care center. J Lab Physicians. 2014;6(2):96-101.
Crossref - Rajni E, Chaudhary P, Garg VK, Sharma R, Malik M. A complete clinico-epidemiological and microbiological profile of candidemia cases in a tertiary-care hospital in Western India. Antimicrob Steward Healthc Epidemiol. 2022;2(1):e37.
Crossref - Selvan P, Vajravelu LK, Mohanraj H, Ramakrishna MS. Monitoring the Spectrum of Candidemia and its Anti-fungal Resistance in A Tertiary Care Centre – An Emerging Global Alarm. J Pure Appl Microbiol. 2022;16(4):2704-2711.
Crossref - Ajenjo H MC, Aquevedo S A, Guzman D AM, et al. Perfil epidemiologico de la candidiasis invasora en unidades de pacientes criticos en un hospital universitario [Epidemiologial profile of invasive candidiasis in intensive care units at a university hospital]. Rev Chilena Infectol. 2011;28(2):118-122
Crossref - Tan BH, Chakrabarti A, Li RY, et al. Incidence and species distribution of candidaemia in Asia:a laboratory-based surveillance study. Clin Microbiol Infect. 2015;21(10):946-953.
Crossref - Shastri PS, Shankarnarayan SA, Oberoi J, Rudramurthy SM, Wattal C, Chakrabarti A. Candida auris candidaemia in an intensive care unit – Prospective observational study to evaluate epidemiology, risk factors, and outcome. J Crit Care. 2020;57:42-48.
Crossref - Chongtham U, Athokpam DC, Singh RM. Isolation, identification and antifungal susceptibility testing of candida species: A cross-sectional study from Manipur, India. J Clin Diagn Res. 2022;16(4):DC09-DC14.
Crossref - Saiprom N, Wongsuk T, Oonanant W, Sukphopetch P, Chantratita N, Boonsilp S. Characterization of Virulence Factors in Candida Species Causing Candidemia in a Tertiary Care Hospital in Bangkok, Thailand. J Fungi (Basel). 2023;9(3):353.
Crossref - Chin VK, Foong KJ, Maha A, et al. Candida albicans isolates from a Malaysian hospital exhibit more potent phospholipase and haemolysin activities than non-albicans Candida isolates. Trop Biomed. 2013;30(4):654-662.
- Ghannoum MA. Potential role of phospholipases in virulence and fungal pathogenesis. Clin Microbiol Rev. 2000;13(1):122-143.
Crossref - Sachin CD, Ruchi K, Santosh S. In vitro evaluation of proteinase, phospholipase and haemolysin activities of Candida species isolated from clinical specimens.
Int J Med Biomed Res. 2012;1(2):153-157. - Sharma Y, Chumber SK, Kaur M. Studying the Prevalence, Species Distribution, and Detection of In vitro Production of Phospholipase from Candida Isolated from Cases of Invasive Candidiasis. J Glob Infect Dis. 2017;9(1):8-11.
Crossref - Furlaneto MC, Favero D, Franca EJG, Furlaneto-Maia L. Effects of human blood red cells on the haemolytic capability of clinical isolates of Candida tropicalis. J Biomed Sci. 2015;22(1):13.
Crossref - Galan-Ladero MA, Blanco MT, Sacristan B, Fernandez-Calderon MC, Perez-Giraldo C, Gomez-Garcia AC. Enzymatic activities of Candida tropicalis isolated from hospitalized patients. Med Mycol. 2010;48(1):207-210.
Crossref - Nouraei H, Pakshir K, ZareShahrabadi Z, Zomorodian K. High detection of virulence factors by Candida species isolated from bloodstream of patients with candidemia. Microb Pathog. 2020;149:104574.
Crossref - Badran EF, Al Baramki JH, Al Shamyleh A, Shehabi A, Khuri-Bulos N. Epidemiology and clinical outcome of candidaemia among Jordanian newborns over a 10-year period. Scand J Infect Dis. 2008;40(2):139-144.
Crossref - Sriphannam C, Nuanmuang N, Saengsawang K, Amornthipayawong D, Kummasook A. Anti-fungal susceptibility and virulence factors of Candida spp. isolated from blood cultures. J Mycol Med. 2019;29(4):325-330.
Crossref - Cavalheiro M, Teixeira MC. Candida Biofilms: Threats, Challenges, and Promising Strategies. Front Med. 2018;5:28.
Crossref - Tulasidas S, Rao P, Bhat S, Manipura R. A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections. Infect Drug Resist. 2018;11:2443-2448.
Crossref - Sasani E, Khodavaisy S, Rezaie S, Salehi M, Yadegari MH. The relationship between biofilm formation and mortality in patients with Candida tropicalis candidemia. Microb Pathog. 2021;155:104889.
Crossref - Bhattacharjee P. Epidemiology and antifungal susceptibility of Candida species in a tertiary care hospital, Kolkata, India. Curr Med Mycol. 2016;2(2):20-27.
- Siopi M, Tarpatzi A, Kalogeropoulou E, et al. Epidemiological Trends of Fungemia in Greece with a Focus on Candidemia during the Recent Financial Crisis:a 10-Year Survey in a Tertiary Care Academic Hospital and Review of Literature. Antimicrob Agents Chemother. 2020;64(3):e01516-19.
Crossref - Giri S, Kindo AJ, Kalyani J. Candidemia in intensive care unit patients: a one year study from a tertiary care center in South India. J Postgrad Med. 2013;59(3):190-195.
Crossref - Lee Y, Puumala E, Robbins N, Cowen LE. Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond. Chem Rev. 2021;121(6):3390-3411.
Crossref - Gautam G, Rawat D, Kaur R, Nathani M. Candidemia: Changing dynamics from a tertiary care hospital in North India. Curr Med Mycol. 2022;8(1):20-25.
Crossref - Solomon DA, Nyerere AK, Kanyua A, Ngugi CW. Prevalence, Species Distribution and Antifungal Susceptibility Profile of Candida Species Isolated from Bloodstream of Critical Care Unit Patients in a Tertiary Care Hospital in Kenya. Open J Med Microbiol. 2021;11(01):32-46.
Crossref
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