Invasive Candidiasis with C diff is Likely Resistant to Antifungal

October 26, 2020
Kenneth Bender, PharmD, MA

Invasive C glabrata found to be most prevalent strain of Candida in stool of patients with C difficile infection, and likely resistant to caspofungin.

Candida glabrata, the second most common cause of invasive candidiasis in the US, was found to be the most prevalent strain of Candida in the stool of patients with Clostridium difficile infection (CDI), and demonstrated a high rate of resistance to the antifungal, caspofungin.

Khursida Begum, PhD, University of Houston College of Pharmacy, Houston Texas reported in the virtual IDWeek 2020 Conference that her group had found C glabarata in 9.2% of stool specimens for patients with CDI, and that 70.2% of these proved resistant to caspofungin.

"The echinocandin class of antifungals, including caspofungin has become the preferred therapy for invasive candidiasis due to C glabrata and other species demonstrating decreased azole susceptibility," Begum explained."Caspofungin resistance has been uncommon, but reports suggest that the incidence is increasing, particularly among C glabrata isolates."

As antibiotic use and overuse can open environments for both C diff and Candida opportunistic infections, Begum suggests that the dysbiosis associated with C diff presents additional opportunity for overgrowth of Candida strains.

Begum and colleagues found that the prevalence of C glabrata in stool of patients with CDI has not been well studied, however, and so sought to investigate the incidence of the potentially pathogenic Candida with CDI, and the susceptibility to antifungal treatment.

The investigators collected stool samples from1,241 patients with CDI, at 2 hospitals in Houston, Texas.The samples were cultured in brain heart infusion (BHI) broth, and then sub-cultured onto selective HardyChrom Candida agar.Isolates were identified with polymerase chain reaction (PCR) testing, and the C glabrata isolates were screened for caspofungin resistance on Muller-Hinton agar.

Begum reported that 14.8% (184/1,241) samples were culture positive for Candida spp.C glabrata was the most prevalent, in 9.2% of samples, followed by C albicans in 2.3%, C tropicalis in 1.6%, C parapsilosis in 1.2% and C krus ei in 0.6%.

The majority of C glabrata isolates (70.2%, 80/114) were caspofungin resistant.

"The results of this study showed that colonization of C glabrata is common in patients with CDI and could be a source of antifungal-resistant pathogens," Begum reported.

In their review of the emergence of resistant Candida species, Andrea Cortegiani, MD , Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy, and colleagues, note that resistance to azole remains uncommon in C albicans, estimating an occurrence in less that 5% of clinical infections, but is found in 4 to 16% of C glabrata infections.

Cortegliani and colleagues note that echinocandin resistance is associated with cross-resistance to azoles.They cite one study in which echinocandin resistance increased from 4.9 to 12.3%, and resistance to fluconazole from 18 to 30% in a 10-year period.

"Acquired resistance following echinocandin exposure appears to be on the rise," Cortegliani and colleagues indicate, "and the emergence of multi-resistant species among C glabrata and the novel pathogen Candida auris poses a serious threat to critically ill patients."

Cortegliani and colleagues are hopeful that development of new glucan-synthase inhibitors, which are structurally different from echinocandins, will prove to be an effective option for multidrug resistant C glabrata.