Higher incidence of C. glabrata bloodstream infections in patients with diabetes indicates potential fluconazole resistance

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In a recent study published in the Journal of the Royal College of Physicians of Edinburgh, researchers analyzed data collected over ten years to understand the clinical characteristics, epidemiology, outcomes, and management of bloodstream Candida infections in diabetes patients.

Study: Epidemiology, management and outcome of candidaemia in patients with diabetes. Image Credit: Kateryna Kon/Shutterstock
Study: Epidemiology, management and outcome of candidaemia in patients with diabetes. Image Credit: Kateryna Kon/Shutterstock

Background

The species of the yeast genus Candida are the predominant cause of fungal infections in hospital settings. For immunocompromised patients, candidemia can also cause death. The common candidemia-causing species are C. albicans, C. parapsilosis, C. glabrata, C. krusei, and C. tropicalis. While some species can be treated with fluconazole, others such as C. glabrata are becoming resistant and C. krusei is inherently resistant. Furthermore, although echinocandins such as micafungin, anidulafungin, and caspofungin are effective against most Candida species, they cannot be administered orally.

Patients with diabetes are especially susceptible to candidemia because of the increased antibiotic treatments and integument disruption due to neurological injury. Furthermore, hyperglycemia reduces the neutrophil function that normally kills yeast cells. Given the increased susceptibility of diabetes patients to candidemia, it is important to understand the epidemiology, outcomes, and treatments for Candida infections.

About the study

In the present study, researchers conducted a retrospective analysis of 10 years of data consisting of documented cases of bloodstream Candida infections. In addition to information on the yeast species identity and antifungal susceptibility, the analyzed data also comprised patient demographic information, health conditions such as diabetes and cancer, previous antifungal prescriptions and use, age, hemodynamic instability, echocardiographs, ophthalmoscopy results, and information on central venous catheters.

The European Confederation of Medical Mycology (ECMM) has also proposed a point-based scoring system to evaluate clinical management quality. This system assigns scores based on criteria such as blood culture volume, identification of yeast species, testing the yeast cultures for antifungal resistance, treatment with echinocandins, ophthalmoscopy, echocardiogram, time taken to remove central venous catheters if present, and many more. These criteria were used to assign scores for patients who died on antifungal medications.

Results

The results reported 200 cases of candidemia, of which 32% (64) were patients with diabetes. A total of 204 Candida isolates were obtained from the 200 cases, with four patients being concurrently infected with two Candida species. Of these, the number of C. albicans isolates was the highest (86), followed by C. glabrata (67) and C. parapsilosis (32).

Compared to candidemia patients without diabetes, the diabetic patients with Candida infections were younger (average age of 58.7 compared to 65.5) and less likely to have cancer. Furthermore, diabetic candidemia patients had a higher likelihood of having C. glabrata infections than C. albicans infections, although the difference compared to non-diabetic patients was not significant.

While the treatments did not differ between diabetic and non-diabetic candidemia patients, with both being treated with either fluconazole or echinocandins, the 30 and 90-day survival rates of diabetic patients were significantly higher than that of non-diabetic patients (82.8% compared to 64.4%). Furthermore, the ECMM scores indicated that the clinical management of Candida infections in diabetic and non-diabetic patients was similar.

The authors believe that based on the results from the present study and other studies, the higher frequency of C. glabrata infections in patients with diabetes could indicate a selection pressure generated from the use of fluconazole and other azoles. Patients with diabetes are often treated with azoles for other fungal infections, such as vaginitis and urinary tract infections, with Candida. The susceptibility of C. albicans to fluconazole could lead to the prevalence of C. glabrata infections in the bloodstream.

While echinocandins are more effective against C. glabrata infections, only 54.6% of the diabetic patients in this study were prescribed echinocandin treatment. Moreover, the ECMM recommends echinocandins as the first line of therapy for Candida infections. In this study, however, many patients were treated for candidemia before echinocandins became commonly available, which explains why only half the diabetic cohort was prescribed echinocandins. Nevertheless, the authors believe this finding highlights the need to review the prescription practices in treating candidemia.

Conclusions

To summarize, the study evaluated ten years of documented candidemia cases to understand the epidemiology, outcomes, and management of Candida infections in patients with diabetes.

The results reported that candidemia patients with diabetes were more likely to be infected with C. glabrata than C. albicans, compared to non-diabetic candidemia patients. While the clinical management of candidemia did not differ between diabetic and non-diabetic patients, the diabetic candidemia patients had significantly higher 30 and 90-day survival rates.

The higher incidence of C. glabrata infections in diabetic patients indicates the possible selection pressure due to fluconazole resistance. It highlights the need to review initial therapy prescription practices for treating Candida infections.

Journal reference:
Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

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