Abstract
Candida auris is identified as an emerging pathogen worldwide. It is multidrug resistant and causes invasive healthcare-associated infections. Our retrospective study was conducted to determine the prevalence and epidemiology of C. auris infections in a tertiary care hospital in Jaipur.
24 clinical C. auris strains were included, most being from urine. The majority patients needed intensive care and had at least one underlying co-morbid condition. A history of broad-spectrum antibiotic or antifungal usage was present in 85%. Fluconazole, voriconazole, amphotericin B and 5-fluorocytosine resistance was seen in 96, 42, 33 and 8% isolates respectively. No echinocandin resistance was noted.
Introduction
There is a steep rise in reports describing invasive infections by multidrug-resistant (MDR) Candida spp. in various medical centres worldwide. The emergence of non-albicans Candida such as Candida glabrata, C. tropicalis and C. auris, resistant to commonly used first- and second-line antifungals, is fast changing the paradigm of nosocomial infections. Amongst these, C. auris has been particularly identified as an emerging pathogen worldwide and the rise of this superbug embodies a serious and growing public health threat.1,2 It is a MDR yeast which causes invasive healthcare-associated infections with mortality rates varying from 30 to 72%, especially in immunocompromised patients. 3 Despite the implementation of enhanced infection prevention and control measures, there is a surge in prevalence of infections caused by this ubiquitous yeast. Having been first described in 2009 after being isolated from the ear canal of a 70-year-old Japanese woman, 4 it is now reported from over 30 other countries including South Korea, India, Pakistan, South Africa, Kenya, Kuwait, Israel, Venezuela, Colombia, United Kingdom, Canada and United States. 2
C. auris is considered a coloniser in intensive care units (ICU) as patients shed viable yeast cells from their skin continuously, thereby contaminating the hospital environment. 5 The Centre for Disease Control and Prevention, USA recommends strict isolation of patients who are either colonised or treated for C. auris. It is the first fungal pathogen categorised as a public health threat. 6 The efficient person-to-person transmission observed for C. auris is striking. 6 An advisory note has also been issued by the Indian Council of Medical Research to ensure active surveillance in Indian hospitals and to arrest the spread of this yeast. 7
It is difficult to identify C. auris with standard laboratory methods and it can be easily missed leading to inappropriate clinical management. 2 Resource-poor countries usually do not have suitable infrastructure required to diagnose it accurately and perform anti-fungal susceptibility testing. Approximately 90, 30 and 5% of clinical C. auris isolates are found resistant to fluconazole, amphotericin B and echinocandins respectively. 2 Changes in epidemiology and evolving resistance profiles have been noted globally and can be explained through irrational antifungal drug use.2,3,5
Despite the ominous nature of infections caused, there is a paucity of data regarding C. auris infections. The available literature mostly emphasises its identification, risk factors associated with acquisition and antifungal susceptibility. Very limited data are available on its disease spectrum and clinical outcomes. Hence this retrospective study was conducted with the following objectives: (1) to determine the prevalence and epidemiology of C. auris infections during the last two years in a tertiary care hospital in Jaipur, (2) to determine the clinical outcome of the patients infected with C. auris and (3) to determine their antifungal susceptibility pattern.
Materials and methods
We conducted a retrospective observational laboratory-based study in the Department of Microbiology, Mahatma Gandhi Medical College & Hospital, Jaipur from July 2018 to June 2020, which is a multispecialty 1400-bedded hospital with 80 ICU beds. Due approval was obtained from our institutional ethical committee [vide no MGMCH/IEC/JPR/2020/182].
All C. auris strains isolated in the laboratory from various clinical samples during the study period were included. Only one isolate per patient was included for study purposes. Electronic patient records were reviewed and data regarding patients’ demographic details, baseline characteristics, comorbidity, laboratory findings and clinical outcome were tabulated in Excel worksheet and analysed.
All Candida spp isolated from various clinical samples were identified by Standard Mycological procedures including:
Isolation on Sabouraud’s dextrose agar (SDA) with chloramphenicol and gentamycin. Germ tube test. Species identification by pigmentation on chromogenic medium (CHROMagar Candida) and corn meal agar.
8
VITEK® 2 COMPACT using VITEK® 2 (ID-YST) cards for identification of yeast and yeast-like organisms.
Antifungal susceptibility testing was performed by broth microdilution using the CLSI M27-A3 guidelines. 9
Results
Distribution of various Candida species from various clinical isolates (n = 576).
A total of 24 clinical C. auris strains cultured from various samples during a two-year period were included in the study, 16 from intensive care and 8 from the high dependency unit. Final identification was done by VITEK 2 Compact System and growth characteristics on CHROMagar and corn meal agar. All C. auris isolates showed smooth, white to cream-coloured colonies on SDA, while they developed pink coloured colonies on CHROMagar Candida medium. Microscopic examination showed ovoid to elongated budding yeast cells occurring singly or in pairs (Figures 1 to 3). Germ tube test was negative.
Candida auris colonies on Sabouraud’s dextrose agar.
The distribution of 24 C. auris strains from various clinical samples is as shown in Figure 4. The median age of patients was 48 years (range 6–85) and included 20 (83%) males. Their median duration of hospital stay was 22 days (range 5–60). Some 17 (74%) had some comorbidity. An invasive procedure was performed in 15 (65%) patients during their hospital stay. Table 2 provides a summary of demographic and epidemiological features of patients found infected with C. auris.
Distribution of Candida auris isolates from various clinical samples (n = 24). Summary of demographic and epidemiological features of 24 patients with Candida auris infection. ICU: intensive care unit; HDU: high dependency unit.
A total of 84% patients had received broad spectrum antibiotics in the preceding three months; 17, 13 and 75% had received corticosteroids, chemotherapy and anti-fungal drugs respectively. Correlation with various associated risk factors is shown in Figure 5.
Correlation of Candida auris infection with various risk factors.
Anti-fungal susceptibility pattern was determined for all isolates and is presented in Figure 6. Fluconazole, voriconazole, amphotericin B and 5-fluorocytosine resistance was seen in 96, 42, 33 and 8% isolates respectively. No resistance to echinocandins was noted.
Antifungal resistance pattern of Candida auris isolates.
Number of Candida auris isolates and their respective clinical outcome from different clinical samples.
Discussion
Evidence suggests that C. auris has a propensity to spread rapidly within and between health care set-ups. Recent isolation of C. auris from the natural aquatic environment in India suggest that this yeast can survive outside the human host too. 10 In the current scenario of its high prevalence and high rate of resistance, strict infection control protocols are required to prevent the transmission of C. auris in hospitals. Although excellent activity of echinocandins against C. auris has been demonstrated, this MDR yeast can still persist in colonised patients in hospital settings. Prior antifungal exposure exerts selective pressure for C. auris. It is essential to devise effective measures for decontamination of patients to prevent further inter and intra hospital transmission.
Our study has a few limitations. Being retrospective in nature, poor control on various confounding factors is unavoidable. We may have missed a few cases. Diagnosis and antifungal susceptibility testing of this organism in a resource-limited laboratory is a challenge. There is ample evidence that C. auris can be misidentified as C. haemulonii, C. duobushaemulonii, C. lusitaniae, etc. Subgroup analysis and comparison of clinical details of C. auris and non-C. auris infections would have helped to understand the associated risk factors better.
However, the strength of our study lies in the fact that it is the first from Western India presenting objective evidence of presence of this notorious yeast in our healthcare settings. It will serve to sensitise clinicians and microbiologists alike to sharpen surveillance mechanisms to detect its presence and development of an empirical antifungal therapy once infection is diagnosed.
Candida auris colonies on CHROMagar Candida. Gram stain of Candida auris under 100× lens.
Footnotes
Institutional ethical committee
Approval was obtained from our institutional ethical committee.
Author contributions
Daisy Bacchani: Literature search, data acquisition and manuscript writing; Ekadashi Rajni: Concept, design, literature search, data acquisition, manuscript editing and review; Vishnu K Garg: Data acquisition and manuscript review; Richa Sharma: Manuscript editing and review; and Ved P Mamoria: Manuscript review. The manuscript has been read and approved by all the authors. The requirements for authorship as stated earlier in this document have been met. The manuscript, or parts of it, have not been submitted elsewhere for publication.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
