Candida haemulonii complex, an emerging threat from tropical regions?

Abstract

Background: Candida haemulonii complex-related species are pathogenic yeasts closely related to Candida auris with intrinsic antifungal resistance, but few epidemiological data are available.

Methodology/principal findings: We analyzed clinical and demographic characteristics of patients with fungemia due to C. haemulonii complex and related species (C. pseudohaemulonii, C. vulturna) reported in France during 2002-2021, and compared them to data of C. parapsilosis fungemia, as they all can be commensal of the skin. We also conducted a study on adult inpatients and outpatients colonized by C. haemulonii complex, managed at the University Hospital of Martinique during 2014-2020. Finally, we performed a literature review of fungemia due to C. haemulonii complex and related species reported in Medline (1962-2022). In total, we identified 28 fungemia due to C. haemulonii complex in France. These episodes were frequently associated with bacterial infection (38%) and high mortality rate (44%), and differed from C. parapsilosis fungemia by their tropical origin, mainly from Caribbean and Latin America. All isolates showed decreased in vitro susceptibility to amphotericin B and fluconazole. In Martinique, we found that skin colonization was frequent in the community population, while colonization was strongly associated with the presence of foreign devices in ICU patients. The literature review identified 274 fungemia episodes, of which 56 were individually described. As in our national series, published cases originated mainly from tropical regions and exhibited high crude mortality.

Conclusions/significance: Multidrug-resistant C. haemulonii complex-related species are responsible for fungemia and colonization in community and hospital settings, especially in tropical regions, warranting closer epidemiological surveillance to prevent a potential C. auris-like threat.

Fig 1. Susceptibility profiles to antifungals of the strains of the French fungemia series.

By EUCAST broth micro dilution reference method. C. duobushaemulonii = 7, C. haemulonii sensu stricto = 13, C. vulturna = 3. Bold black bar: median MIC value; Blue diamond: mean MIC value.

Fig 2. Explanatory models for the occurrence and the mortality of the fungemia.

a. Explanatory model for the occurrence of C. haemulonii complex, C. pseudohaemulonii or C. vulturna fungemia rather than C. parapsilosis (adjusted odds ratio from logistic regression coefficients with 95% confidence interval). b. Explanatory model for the death within 3 months of C. haemulonii complex, C. pseudohaemulonii, C. vulturna or C. parapsilosis fungemia (adjusted odds ratio from logistic regression coefficients with 95% confidence interval).

Fig 3. World mapping of cases of fungemia due to C. haemulonii complex, C. pseudohaemulonii or C. vulturna.

According to our case series (obtained from the YEASTS program 2002–2021 and the RESSIF Network 2012–2021) and the literature review (Medline, 1962–2022). References are with the S3 Fig. Map created from fla-shop.com (https://www.fla-shop.com/svg/, CC BY 4.0 license) modified with inkscape software.