Successful expanded access use of rezafungin, a novel echinocandin, to eradicate refractory invasive candidiasis in a liver transplant recipient

Abstract

We report herein successful eradication of refractory intra-abdominal candidiasis in a liver transplant recipient with the use of rezafungin, a novel echinocandin, under compassionate use. A woman in her sixties with alcoholic cirrhosis was treated for spontaneous bacterial peritonitis (SBP) at another hospital, then readmitted there with reaccumulation of ascites. A peritoneal drain was placed and she subsequently developed shock requiring vasopressor support, as well as presumed hepatorenal syndrome, and was started on octreotide, midodrine and albumin, as well as continuous renal replacement therapy (CRRT). She received piperacillin/tazobactam 2.25 g IV every 6 h due to concern for recurrent peritonitis, thought to be secondary to the catheter. Peritoneal fluid culture grew yeast, prompting initiation of anidulafungin. She was transferred to our hospital, at which time her yeast was identified as Candida krusei. The peritoneal catheter was removed and she completed a subsequent 2 week course of micafungin and piperacillin/tazobactam. She was listed for liver transplantation with a model for end-stage liver disease (MELD) score of 38 and underwent transplantation 2 days later. She received methylprednisolone 500 mg IV with the transplant and was maintained on tacrolimus, mycophenolate mofetil and a prednisone taper. Intra-operatively, peritoneal fluid was noted to be cloudy, raising concern of recurrent peritonitis, so she received 14 days of piperacillin/tazobactam and micafungin, though no organisms grew in culture. She was discharged to a post-acute care facility briefly before being readmitted with worsening abdominal pain. CT of the abdomen showed a large abdominal fluid collection most consistent with haematoma and measuring 12.2 × 21.6 × 23.5 cm. Two litres of bloody fluid was drained with cultures again growing C. krusei (MIC of micafungin ≤0.25 mg/L and MIC of voriconazole 0.12 mg/L; testing according to CLSI M38-A2). She resumed piperacillin/tazobactam and micafungin and underwent abdominal washout, during which she was found to have thick-walled abscesses within the abdomen and pelvis. Intra-operative cultures from unroofed collections also grew C. krusei in addition to Klebsiella oxytoca resistant only to trimethoprim/sulfamethoxazole and cefazolin. In spite of this, a repeat CT scan 4 days following washout showed reaccumulation of fluid collections, the largest measuring 3.4 × 14.9 cm, with progression of several large loculated fluid collections within the abdomen, pelvis and abdominal wall.