Epidemiology and susceptibility of Nakaseomyces (formerly Candida) glabrata bloodstream isolates from hospitalised adults in South Africa.

During 2016-2017, Nakaseomyces glabrata (formerly Candida glabrata) caused 14% of cases of candidaemia in South Africa. We aimed to describe the clinical characteristics of adults with N. glabrata candidaemia at 20 sentinel hospitals (accounting for 20% (172/917) of cases) and the antifungal susceptibility of the corresponding isolates. A higher proportion of patients with N. glabrata candidaemia were older (median age: 55 years [interquartile range (IQR): 41-65 years] vs. 49 years [IQR: 35-63 years]; p = 0.04), female (87/164, 53% vs. 283/671, 42%; p = 0.01), admitted to a public-sector hospital (152/172, 88% vs. 470/745, 63%; p < 0.001), treated with fluconazole only (most with suboptimal doses) (51/95, 54% vs. 139/361, 39%; p < 0.001), and had surgery (47/172, 27% vs. 123/745, 17%; p = 0.001) and a shorter hospital stay (median 7 days [IQR: 2-20 days] vs. 13 days [IQR: 4-27 days]; p < 0.001) compared to patients with other causes of candidaemia. Eight N. glabrata isolates (6%, 8/131) had minimum inhibitory concentrations in the intermediate or resistant range for ≥ 1 echinocandin and a R1377K amino acid substitution encoded by the hotspot 2 region of the FKS2 gene. Only 11 isolates (8%, 11/131) were resistant to fluconazole. Patients with confirmed N. glabrata candidaemia are recommended to be treated with an echinocandin (or polyene), thus further guideline training is required.

Nakaseomyces (formerly Candida) glabrata is a yeast-like fungus that forms part of the commensal gut flora and among people with certain risk factors, can invade into the bloodstream. Nakaseomyces glabrata is a relatively more common cause of candidaemia in high-income vs. low- and middle-income countries. There are no N. glabrata clinical isolates that are considered susceptible to fluconazole, and thus echinocandins are recommended for treatment. However, echinocandin resistance is emerging. We described the characteristics of South African patients with N. glabrata bloodstream infections and the antifungal susceptibility of corresponding isolates. We found that patients infected with N. glabrata were more likely to be older, female, admitted to public hospitals and to be post-surgery and these patients were also more likely to be treated with fluconazole monotherapy and to have stayed a shorter time in hospital compared to patients infected with other Candida species. Only 6% of N. glabrata isolates were echinocandin-resistant with mutations in specific resistance genes that we have found in South African N. glabrata isolates previously. Eight percent of N. glabrata isolates were resistant to fluconazole and the remainder were in the susceptible dose dependent category, requiring higher fluconazole treatment doses. Patients with confirmed N. glabrata bloodstream infection should ideally be treated with an echinocandin or polyene rather than fluconazole and training is required for doctors treating these patients.

Breakthrough candidemia with hematological disease: Results from a single-center retrospective study in Japan, 2009-2020.

Breakthrough candidemia (BrC) is a significant problem in immunocompromised patients, particularly those with hematological disorders. To assess the characteristics of BrC in patients with hematologic disease treated with novel antifungal agents, we collected clinical and microbiological information on said patients from 2009 to 2020 in our institution. Forty cases were identified, of which 29 (72.5%) received hematopoietic stem cell transplant (HSCT)-related therapy. At BrC onset, the most administered class of antifungal agents were echinocandins, administered to 70% of patients. Candida guilliermondii complex was the most frequently isolated species (32.5%), followed by C. parapsilosis (30%). These two isolates were echinocandin-susceptible in vitro but had naturally occurring FKS gene polymorphisms that reduced echinocandin susceptibility. Frequent isolation of these echinocandin-reduced-susceptible strains in BrC may be associated with the widespread use of echinocandins. In this study, the 30-day crude mortality rate in the group receiving HSCT-related therapy was significantly higher than in the group not receiving it (55.2% versus 18.2%, P = .0297). Most patients affected by C. guilliermondii complex BrC (92.3%) received HSCT-related therapy and had a 30-day mortality rate of 53.8%; despite treatment administration, 3 of 13 patients had persistent candidemia. Based on our results, C. guilliermondii complex BrC is a potentially fatal condition in patients receiving HSCT-related therapy with echinocandin administration.

This retrospective study was conducted at a Japanese center specializing in hematopoietic stem cell transplants and found that the rare pathogen Candida guilliermondii complex was the most common cause of breakthrough candidemia, with high mortality rate, which is a concern for transplant patients.