Cytomegalovirus Resistance in Solid Organ Transplant Recipients

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Abstract
Background: Cytomegalovirus (CMV) resistance remains a significant challenge in solid organ transplant (SOT) recipients and is associated with morbidity, mortality, and graft loss. Contemporary data describing institutional patterns of resistant CMV and real-world management practices remain limited. Methods: We conducted a retrospective review of SOT recipients with confirmed CMV resistance at a tertiary care transplant center between 2019 and 2023. Clinical characteristics, antiviral exposure, timing of Transplant Infectious Diseases (TID) consultation, and outcomes were abstracted through structured chart review. CMV resistance was defined by the presence of UL97 or UL54 mutations on genotypic testing. Results: Seventeen SOT recipients with confirmed CMV resistance were identified, most of whom were CMV donor-positive/recipient-negative and receiving valganciclovir prophylaxis at the time of resistance detection. The median time from transplant to CMV detection was 129 days (IQR: 56–167). Resistance was detected on the first genotypic assay in all cases, with UL97 mutations present in all patients. Among patients receiving prophylaxis at the initial CMV episode, 64% met criteria for valganciclovir underdosing. Early transplant infectious diseases consultation at the initial infection occurred in 35% of cases. Conclusions: In this single-center study, CMV resistance was detected during valganciclovir prophylaxis, often in the setting of underdosing during periods of dynamic renal function. Resistance was predominantly mediated by UL97 mutations and detected on initial genotypic testing. These findings describe care processes, including valganciclovir dose reassessment during dynamic renal function and earlier transplant infectious diseases involvement, that warrant further evaluation for improving CMV management in transplant recipients.

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