Successful use of foscarnet during cvvhd to diminish cytomegalovirus viral load

Introduction: Foscarnet is the treatment of choice for ganciclovir-resistant cytomegalovirus (CMV), but use is limited by significant nephrotoxicity. Foscarnet dosing recommendations in continuous venovenous hemodialysis (CVVHD) based on circuit elimination from contemporary machines is lacking, and limited data exist to guide foscarnet use in CVVHD. Description: A 48 year-old male presented to the hospital approximately five months after kidney transplantation with persistent diarrhea and new onset chest pain. He soon developed acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation and renal failure requiring CVVHD. As the patient’s CMV serostatus at the time of transplantation was D+/R+, he was prescribed prophylactic valganciclovir 450mg daily post-transplant. Infectious workup during admission revealed a serum CMV viral load of >1,000,000 IU/mL and bronchial fluid CMV viral load of 17,950 IU/mL. Given the breakthrough viremia and presumptive CMV gastritis and pneumonitis, IV ganciclovir was initiated on hospital day 3. Two days later the patient was empirically escalated to foscarnet due to concern for ganciclovir resistance. Foscarnet 80 mg/kg dosed using adjusted body weight (ABW) q24h was initiated based on dialysate flow rate of 3.5 L/hr, blood flow rate of 300 mL/min, and presumed foscarnet protein binding of 15-20%. This was subsequently increased to 50 mg/kg ABW q12h. Both doses were tolerated well. Genotypic assay ultimately revealed a ganciclovir-resistant strain of CMV containing the UL97:C592G mutation. Bronchial fluid CMV viral load became undetectable and serum viral load reached 2425 IU/mL at 14 and 20 days after foscarnet initiation, respectively. However, the patient expired 28 days after admission due to complications including ARDS and secondary Pseudomonas aeruginosa pneumonia. Discussion: Foscarnet therapy successfully diminished both serum and bronchial fluid viral load in a post-transplant patient requiring CVVHD. Optimal dosing strategies remain unclear. Dosing based on clinical response and estimating clearance utilizing circuit flow rate and fraction unbound of drug may allow for successful extrapolation of manufacturer recommendations during CVVHD to effectively decrease CMV viral load.