Pharmacokinetic Study of Rezafungin in Patients With Suspected Intra-Abdominal Candidiasis

Overview

Intra-abdominal candidiasis is the most frequent candidiasis infection after candidemia. The studies that have positioned echinocandins as the first therapeutic option in candidiasis have been carried out mainly in patients with candidemia. Peritoneal concentrations of caspofungin, micafungin and anidulafungin are clearly above the MICs of most Candida spp but are below the threshold for selection of resistant mutants, which has been argued by some researchers as a risk for the control of intra-abdominal infections with poor control of the focus and selection of resistant mutants, observed in Candida spp isolates at the peritoneal level in relation to isolates at the blood culture level. Rezafungin, with its special pharmacokinetics, achieves higher tissue concentrations, including hepato-splenic and other abdominal organs, than the other echinocandins. Experimental studies have confirmed that the concentration of rezafungin at the level of the inflammatory focus in abdominal infections is higher than in the surrounding healthy tissue and higher than those achieved by micafungin. Finally, the biofilm activity of rezafungin is very high, clearly superior to fluconazole and possibly higher than that of other echinocandins.

Intra-abdominal candidiasis is the most common candidal infection after candididaemia. Studies that have positioned echinocandins as the first therapeutic option in candidiasis have been conducted primarily in patients with candidaemia. Peritoneal concentrations of caspofungin, micafungin and anidulafungin are clearly above the MICs of most Candida spp but are below the threshold for selection of resistant mutants, which has been argued by some researchers as a risk for the control of intra-abdominal infections with poor control of the focus and selection of resistant mutants, observed in Candida spp isolates at the peritoneal level relative to isolates at the blood culture level. Rezafungin has the characteristic of having a modified chemical structure that gives it greater stability and a prolonged half-life, allowing the drug to be administered less frequently on a weekly rather than daily basis. This results in greater clearance of candidemia and greater penetration and persistence in tissues compared to other echinocandins, and improves patient adherence to treatment. The efficacy of Rezafungin has already been evaluated in clinical trials, and has been shown to be equal or superior to that of other echinocandins, and because it has a low incidence of cross-resistance with other antifungals, it is an appropriate choice for resistant fungal infections.