Ganciclovir‐Resistant Cytomegalovirus Infection in Abdominal Solid Organ Transplant Recipients: Case Series and Review of the Literature

Abstract

Ganciclovir-resistant cytomegalovirus (GR-CMV) is emerging as a significant infection in the abdominal transplant population. GR-CMV is difficult to manage, and treatment options are limited. We report a descriptive case series of 15 patients who had documented GR-CMV at our center and review the literature on treatment of GR-CMV. The first case in this series was detected in 2012; the majority of cases occurred after January 1, 2014, with approximately 50% occurring in 2015. UL97 and UL54 viral genome mutations were present in 100% and 40% of CMV-infected patients, respectively. GR-CMV infection occurred ≤ 1 year posttransplantation in 11 patients (73%). All patients experienced dose reduction of valganciclovir (the oral prodrug of ganciclovir) before the development of GR-CMV. Initial treatment for GR-CMV included a variety of regimens, all including reduction in maintenance immunosuppression. Of the 6 patients with detectable GR-CMV by polymerase chain reaction (PCR) who were discharged without GR-CMV treatment and had a length of stay (LOS) less than 14 days, 83% were subsequently readmitted for treatment of GR-CMV within 2 months (60% in < 20 days); none received leflunomide. Of six patients with a LOS ≥ 14 days, 80% had CMV PCR below quantification on hospital discharge, and only one patient was readmitted in less than 20 days; 83% received leflunomide. Following GR-CMV, there was a 50% rejection incidence, 27% graft loss, and 20% mortality. For patients with more than three admissions for GR-CMV treatment, 100% had a major complication: 60% rejection, 20% graft loss, and 40% mortality. Common clinical characteristics of patients with GR-CMV included high-risk serostatus, lymphocyte depletion, and history of valganciclovir dose reduction. Overall, outcomes were poor. It appears that hospital readmission rate was reduced when CMV was treated to negativity with an initial treatment regimen of reduced immunosuppression, foscarnet, intravenous immunoglobulins, and leflunomide.

Single‐center, real‐world experience with granulocyte colony‐stimulating factor for management of leukopenia following kidney transplantation

“…12 In the solid organ transplant population, G-CSF has also been utilized to more quickly achieve WBC count recovery during leukopenia. 6,[17][18][19] Through retrospective review, we sought to describe overall management of leukopenia including dosing and efficacy of G-CSF in kidney transplant recipients in both the inpatient and outpatient setting at our institution. 1,2,5,9,[13][14][15][16] In patients with leukopenia secondary to CMV infection, G-CSF may also prevent the need for ganciclovir or VGCV dose reduction during treatment, which has been associated with development of ganciclovir-resistant CMV.…”

“…1,2,5,9,[13][14][15][16] In patients with leukopenia secondary to CMV infection, G-CSF may also prevent the need for ganciclovir or VGCV dose reduction during treatment, which has been associated with development of ganciclovir-resistant CMV. 6,[17][18][19] Through retrospective review, we sought to describe overall management of leukopenia including dosing and efficacy of G-CSF in kidney transplant recipients in both the inpatient and outpatient setting at our institution. Attention was also paid to potential complications of leukopenia or its management, such as infection or acute rejection.…”

Impact of High‐Dose Acyclovir Cytomegalovirus Prophylaxis Failure in Abdominal Solid Organ Transplant Recipients

“…Previously published literature reports failure rates of standard‐dose VGC (900 mg/day) to be essentially nonexistent in renal transplant recipients in the setting of good compliance, even in the high‐risk D+/R− population . However, VGC is associated with significant tolerance issues, and more recently, antiviral drug resistance, making alternative agents desirable .…”

“…Valganciclovir (VGC) is the preferred antiviral for prophylaxis in transplant recipients who were previously exposed to CMV (R+); however, VGC is associated with significant cytotoxicity . In addition, VGC dose reduction to avoid cytotoxicity was associated with the emergence of CMV resistance . Recent literature suggests that patients stratified into a low to moderate risk subgroup may obtain sufficient prophylaxis with less toxic therapies, such as high‐dose acyclovir (HD‐A) .…”

Management of Antimicrobial Agents in Abdominal Organ Transplant Patients in Intensive Care Unit

“…Oral [12••]. While the incidence of ganciclovirresistant cytomegalovirus in patients on prophylactic valganciclovir is as low as 0-3%, the incidence of emergence of ganciclovir-resistant cytomegalovirus infection in patients receiving ganciclovir treatment is about 5-12% [58]. For patients whose viral loads fail to decline while on therapy, ganciclovir resistance test is recommended.…”