Pharmacokinetics of echinocandins in suspected candida peritonitis: A potential risk for resistance

Abstract

Introduction: A possible increase in Candida resistance, especially in Candida glabrata, has been speculated according to poor diffusion of echinocandins to peritoneal fluid. Materials/methods: Peritoneal and serum concentrations of caspofungin, micafungin and anidulafungin were analysed in surgical patients with suspected candida peritonitis. After 4 days of starting therapy, serum and peritoneal samples (through peritoneal drainage) were obtained at baseline, 1, 6, 12 and 24 h of drug administration. Micafungin and anidulafungin concentrations were determined using highperformance liquid chromatography (HPLC/F), whereas caspofungin concentrations were established by bioassay. Results: Twenty-three critically ill patients with suspected abdominal fungal infection who were receiving an echinocandin were prospectively recruited. No specific criteria were applied to prescribe one specific echinocandin. No special clinical differences were observed among the three groups of patients. All were receiving antibiotic therapy, 80% required inotropic drugs, and fungal peritonitis was confirmed in 74% of them. The AUC 0_24h (mg  h/L) obtained in serum and peritoneal fluid were: 126.84 and 34.38, 98.52 and 18.83, and 66.9 and 8.78 for anidulafungin, micafungin and caspofungin, respectively. The median concentration in peritoneal fluid ranged from 0.66 to 1.82 mg/mL for anidulafungin, 0.68-0.88 mg/mL for micafungin and 0.21-0.46 mg/mL for caspofungin. Conclusion:The results showed moderate penetration of echinocandins into the peritoneal fluid of these patients. These levels are below the threshold of resistance mutant selection published by other authors. This could justify a potential risk of resistance in patients with prolonged treatment with echinocandins and suboptimal control of abdominal infection.

ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment

“…111 The antifungal treatment of choice for C. albicans is usually fluconazole, whereas other Candida organisms sometimes require an echinocandin (caspofungin, micafungin or anidulafungin) or voriconazole. 367,215 The route of echinocandins administration should be intravenous 243 because of the concern that PD fluid significantly impairs the activity of echinocandins against Candida species biofilm. 368 Voriconazole administration is preferably oral, because of the concern with accumulation of the intravenous vehicle cyclodextrin in dialysis patients.…”

Rectal screening for azole non‐susceptible Candida species in patients undergoing liver transplantation

“…This suggests that Candida rectal swab screening may not be sufficiently sensitive to rule out ANSC colonization, and tailored prophylaxis based on colonization status does not prevent all Candida infections. Furthermore, although human‐derived data are limited, 12 suboptimal peritoneal concentrations of echinocandins have been observed 13 ; hence, it is conceivable that the pharmacokinetics of anidulafungin limited its ability to serve as prophylaxis against abdominal sources of candidiasis.…”

Critical appraisal beyond clinical guidelines for intraabdominal candidiasis

“…To further complicate dosing, in cIAIs there is an impaired tissue penetration which, together with the presence of indwelling surgical drains, may alter drug PK [ 38 ]. Other important covariates in altering effective drug concentrations are body weight, serum albumin concentrations and application of extracorporeal treatments [ 39 , 40 ].…”