gms | German Medical Science

Background: Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality following solid organ transplantation (SOT), and ganciclovir-resistant CMV (ganR-CMV) has been increasingly reported. Previous studies have reported factors associated with development of ganR-CMV but few have systematically focused on outcomes, including morbidity and mortality. An important limitation of prior studies has been a cohort design that compared patients with ganR-CMV with all other patients, making it difficult to assess the specific attributable impact of ganciclovir resistance. To address these limitations, we used a matched case-control study design to examine both risk factors and outcomes in SOT recipients with ganR-CMV compared to ganciclovir susceptible CMV (ganS-CMV) infections.

Methods: We performed a retrospective, case-control study of 37 SOT recipients with ganR-CMV infection matched (3:1) with 109 with ganS-CMV infection, between January 1993 and December 2010. Controls were matched to cases based on CMV donor/recipient serostatus, type of organ transplant, and CMV disease type. UL97 and UL54 genotyping was used to define ganR-CMV. Potential factors associated with development of ganR-CMV included age, gender, race, exposure to ganciclovir, induction and maintenance immunosuppression, time to CMV disease, and allograft rejection. Outcomes included mortality, time to CMV PCR clearance, length of hospitalization (LOS), rejection following CMV infection, and nephrotoxicity.

Results: Median time from transplant to CMV disease in ganR-CMV and ganS-CMV patients was 196 days (range 88-881) and 143 days (range 15-5567 days), respectively. Cases had increased exposure to ganciclovir/valganciclovir (median 153 days versus 91 days in controls, p<0.0001). Mortality at three months and one year following CMV disease diagnosis was statistically significantly increased in the ganR-CMV group (13% vs. 1%, p=0.001; 18% vs. 5%, p=0.05, respectively). Days of hospitalization in the first 3 months following CMV diagnosis and time to clearance of CMV viremia were also increased in patients with ganR-CMV infection (median 9 days vs. 4 days, and median 313 days vs. 66 days, respectively). Nephrotoxicity (GFR decrement of >/= 20%) was more common in the ganR-CMV patients than ganS patients (71% vs. 40%, p=0.001).

Conclusions: This represents the largest matched case-control study comparing SOT recipients with ganR-CMV versus ganS-CMV. These data demonstrate an important attributable negative impact of ganciclovir resistance in SOT recipients, and call for improved strategies for prevention, surveillance, and treatment.