Ganciclovir Dosing Strategies and Development of Cytomegalovirus Resistance in a Kidney Transplant Recipient: A Case Report

• Published in: Transplantation proceedings 2017-09, Vol.49 (7), p.1560-1564
• Main Authors: Echenique, I.A., Beltran, D., Ramirez-Ruiz, L., Najafian, N., Agrawal, N.
• Format: Article
• Language: English
• Subjects: Aged; Antiviral Agents - administration & dosage; Cytomegalovirus - drug effects; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - virology; Cytosine - administration & dosage; Cytosine - analogs & derivatives; Dose-Response Relationship, Drug; Drug Resistance, Viral; Foscarnet - administration & dosage; Ganciclovir - administration & dosage; Humans; Immunoglobulins - drug effects; Isoxazoles - administration & dosage; Kidney - virology; Kidney Transplantation - adverse effects; Male; Organophosphonates - administration & dosage; Postoperative Complications - prevention & control; Postoperative Complications - virology; Tissue Donors
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2017.02.046

In renal transplant recipients, delayed graft function and accompanying renal impairment may lead to therapeutic underexposure of valganciclovir. We describe a case of a cytomegalovirus (CMV)-seronegative kidney transplant recipient from a CMV-seropositive donor, whose course was complicated during valganciclovir prophylaxis by CMV disease, ultimately progressing to ganciclovir, foscarnet, and cidofovir resistance. Assessments and adjustments for renal dysfunction, according to both Cockgroft-Gault and Modification of Diet in Renal Disease study equations, are described. Therapy was complicated by outpatient parenteral therapy with pump-administered antiviral therapy, which may have led to drug underexposure and the fostering of antiviral resistance. Suppression was ultimately achieved in conjunction with reduction in immunosuppressive therapy, CMV immunoglobulin, and initiation of leflunomide. At-risk recipients may benefit from 24 hour creatinine clearance assessments, direct creatinine clearance measurement, or therapeutic drug monitoring. Optimal dosing strategies in recipients with impaired kidney function remain undefined, with limited pharmacokinetic data to date. •Underdosing is a risk for failure of CMV prophylaxis and treatment.•Traditional equations may underestimate renal function in kidney recipients.•Continuous-infusion ganciclovir may lead to low-level drug exposure and resistance.