Introduction

In hospitalized patients, especially in critical care patients, candidemia accounts for considerable morbidity and mortality. It is the most serious systemic infection produced by Candida with a mortality rate of 20-40%, seen frequently in patients with risk factors such as prolonged antibiotic therapy, invasive surgery, indwelling intravenous catheters, prosthetic devices, hyperalimentation fluids, chemotherapy. (1,2)

Majority of candidemia episodes are caused by Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei. A change in the epidemiology of candida infections, characterized by a progressive shift from a predominance of C. albicans to non-albicans Candida species such as C. tropicalis, C. glabrata, and C. krusei has been reported from many countries around the world [3-6]. Among these, C. auris is a newly noticed, multidrug-resistant yeast leading to outbreaks in various geographical locations. (7) This changing scenario is concerning as these species have reduced susceptibilities to antifungal agents. It is observed that C. albicans is usually susceptible to fluconazole, but there is a rise in primary resistance to fluconazole in C. glabrata, C. tropicalis, and C. parapsilosis. (2,6) The situation is more complicated with the arrival of C. auris which is associated with health care infections with high rates of clinical treatment failure. (7)

Knowledge of local species epidemiology and antifungal susceptibility is important when considering therapy. This study was performed to speciate bloodstream Candida isolates by employing MALDI-TOF analysis and to assess their risk factors in patients admitted in our tertiary care hospital.

Materials and Methods

This ambispective study of 2 years' duration was performed from April 2022 to March 2024 with Institutional Ethics Committee approval (FMIEC/CCM/550/2023). Data was retrieved from the laboratory information system. All the blood cultures received in the microbiology laboratory were included in the study. Any repeat isolate from the same patient was excluded from the study.

Blood cultures were processed using Bac T/Alert aerobic culture bottle (bio Mérieux, France) and were incubated for 5 days at 37°C. Blood cultures growing yeast were subjected to Gram stain and sub-cultured on blood agar (HiMedia Laboratories Pvt. Ltd., Mumbai, India). and Sabouraud’s dextrose agar (SDA) (HiMedia Laboratories Pvt. Ltd., Mumbai, India). Species level identification of Candida was performed by using Bruker Daltonics Microflex LT/SH MALDI-MS System (Bruker Daltonics, Germany) with maldi-Biotyper software and MBT Compass data V12.0.0.0_10833. MALDI-TOF identifies the organism based on the unique proteomic pattern comparing with an available, matching pattern in the reference database. (8)

Disk diffusion method was used for antifungal susceptibility testing for azoles. Susceptibility test was done using fluconazole(25µg) and voriconazole(1μg) disks according to clinical laboratory standard institute (CLSI)guidelines. (9,10) Antifungal susceptibility for C. auris was interpreted using C. albicans breakpoints since reference zone diameters are not available in CLSI or European Committee on Antimicrobial Susceptibility Testing (EUCAST). Data was entered in an Excel sheet and analyzed. Categorical variables were expressed in terms of frequencies and percentages and continuous variables were expressed in terms of the median.

Results

During the study period, a total number of 132 (0.74%) Candida isolates from 17,721 blood cultures were isolated. The patients were aged from 14 days to 90 (median age, 52) with predominance of males (59%). Majority were non- albicans Candida accounting for 81.06 % of total candidemia isolates. Among non-albicans Candida, C. tropicalis (31.81%) was the most common candida species isolated followed by C. parapsilosis (20.45%). Isolation rate of C. auris was 13.63% in this study period and most of them were from burns unit (58.3%) (Table 1)

Overall, fifty-nine patients (44.69%) had diabetes mellitus as associated morbidity. Two most common risk factors identified in patients with candidemia were concurrent antibiotic use (95.45%) and use of intravenous(IV) device (51.51%). (Fig. 1)

Figure 1: Comorbidities and Risk factors for candidemia

Susceptibility to both fluconazole and voriconazole was 100% for C. albicans and C. tropicalis isolates. Though the voriconazole susceptibility was 100% in C. parapsilosis, fluconazole susceptibility was lower (88.23%). None of the C. auris isolates were susceptible to fluconazole though the voriconazole susceptibility of 72% was observed.

Discussion

Candidemia is the most common presentation of invasive infections by candida species. Early detection and targeted therapy are important in preventing fatal outcome. Worldwide changing epidemiology of candida species and their susceptibilities warrant the clinicians and microbiologists for an accurate identification of the candida species. (2,3,5)

Etiologies of candidemia are shifting away from C. albicans and heading towards Candida species other than C. albicans which have a high tendency for developing resistance, such as the multidrug-resistant C. auris, which is rapidly disseminating throughout the world. Increased prevalence of non-albicans Candida was observed in our study which is concordant with few other studies from India (5, 6) Among non- albicans Candida, C. tropicalis was the most common isolate followed by C. parapsilosis which is similar to the findings from Singh et al and Abdel-Hamid et al studies. (11,12)

There is a need to assess patients who are at risk of acquiring candida infection for the prevention of adverse outcome of the patients and healthcare burden. Diabetes mellitus and cardiac disease were the most common comorbidities and concurrent antibiotic use was the most common risk factor associated with candidemia in our study which is concordant with a study conducted Deepali et al (13).

We found a high rate of isolation for C. auris (13.63%) in our study which is very concerning. In a study from western India showed C. auris as the most frequent candida species isolated from candidemia patients with the isolation rate of 43%. (7) Burns patients with impaired immune defense and large wounds are at high risk of acquiring C. auris infection from the hospital environment.(14) It is important to identify C. auris accurately so that infection control practices can be followed strictly to control the spread of C. auris strain in the hospital.

In our study, we observed that the fluconazole was the most common antifungal agent used in treatment with an average duration of 2 weeks. Fluconazole with Caspofungin was used for the treatment of candidemia patients with C. auris. The recommended duration of antifungal therapy for uncomplicated candidemia cases should be extended to 2 weeks after the documented clearance of candida from blood stream and the resolution of symptoms. (15)

The increasing isolation of non- albicans Candida, especially high prevalence of C. auris along with fluconazole resistance in non-albicans Candida in this study is of concern. Continuous evaluation is essential for those patients with risk factors to predict the development of candidemia and for the early intervention. Our study findings highlight the need of strengthening hospital infection control practices and implementation of antimicrobial stewardship program in order to prevent the rise in antifungal resistance.

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