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Rezafungin Superior to Micafungin to Treat Resistant Intra-abdominal Candidiasis

Rezafungin is more effective than micafungin in treating FKS-mutant Candida glabrata intra-abdominal candidiasis, investigators with the University of Pittsburgh, VA Pittsburgh Healthcare Systems, and Rutgers New Jersey Medical School found in a recent study.

In research presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2019), the team detailed a study comparing rezafungin, a novel echinocandin in development for the treatment and prevention of fungal infections, with micafungin for treating Candida glabrata that had demonstrated resistance to echinocandins via a FKS gene mutation. 

Contagion® sat down with Minh-Hong Nguyen, MD, professor of medicine at the University of Pittsburgh and an investigstor on the study, to discuss the key findings (see video).

Investigators infected 6-8 week-old female mice with 1x107CFU of Candida glabrata BG2 (wild-type FKS) or 2 clinical isolates with FKS2 mutations (F659S or F659del). Six hours before infection, the mice received either rezafungin (20 mg/kg, single dose IV) or micafungin (5 mg/kg, IV daily x3d). At 3 days (3d) and 7 days (7d) post-infection, mice were sacrificed for burden determination in peritoneal fluid and abscess (IAA).

The minimum inhibitory concentration (MIC) of rezafungin against BG2, F659S, and F659del isolates were ≤0.015, 0.06, and 0.25 µg/mL, respectively. Against the same isolates, micafungin MICs were 0.03, 0.5, and 0.75 µg/mL, respectively. In BG2-infected mice, both rezafungin and micafungin achieved significant reductions compared to controls in mean burdens in PF at both time points.

Rezafungin, though, achieved greater kills than micafungin, with mean PF reductions of 0.83 vs 0.34 (3d), and 0.64 vs 0.35 (7d), and IAA reductions of 1.6 vs 0.21 (3d) and 1.27 vs 0.45 (7d) (p<0.03 for both), investigators reported.

“[Rezafungin] also caused significant reductions in mean burdens of F659S compared with controls in PF (0.71 at 3d and 0.5 at 7d), and IAA (1.28 at 3d and 1.21 at 7d),” the study reads. “In contrast, micafungin caused less reductions in burdens of F659S compared with controls in PF (0.29 at 3d and none at 7d), and IAA (0.48 at 3d and 0.4 at 7d).”

The mean reductions for rezafungin and micafungin against F659del compared with controls were: PF: 1.60 vs 1.02 (3d), and 0.93 vs 0.6 (7d); IAA: 1.28 vs 1.38 (3d), and 1.67 vs 1.48 (7d).

Investigators noted rezafungin’s long plasma half-life, making it ideal for prolonged dosing intervals. It also attained better penetration for prolonged duration within necrotic cores than micafungin.

“[Rezafungin] achieved greater and more prolonged penetration at sites of intra-abdominal candidiasis than micafungin, which correlates with significantly greater activity against FKS-mutant Candida glabrata clinical strains,” investigators concluded.”[Rezafungin] demonstrated greater effectiveness with less frequent dosing than micafungin, supporting extended dosing intervals in patients, and promising use as treatment and prophylaxis against intra-abdominal candidiasis.”

The study, “Rezafungin Is More Effective Than Micafungin in Treating of FKS-Mutant Candida glabrata Intra-abdominal Candidiasis,” was presented in an oral session on Monday, April 15, 2019, at ECCMID 2019 in Amsterdam, the Netherlands.
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