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. 2017 Jul 1;65(1):57-63.
doi: 10.1093/cid/cix259.

Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients

Cynthia E Fisher  1   2 , Janine L Knudsen  1 , Erika D Lease  1   3 , Keith R Jerome  2   4 , Robert M Rakita  1 , Michael Boeckh  1   2 , Ajit P Limaye  1
Affiliations

Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients

Cynthia E Fisher et al. Clin Infect Dis. .

Abstract

Background: Ganciclovir-resistant (ganR) cytomegalovirus (CMV) is an emerging and important problem in solid organ transplant (SOT) recipients. Only through direct comparison of ganR- and ganciclovir-sensitive (ganS) CMV infection can risk factors and outcomes attributable specifically to ganciclovir resistance appropriately be determined.

Methods: We performed a retrospective, case-control (1:3) study of SOT recipients with genotypically confirmed ganR-CMV (n = 37) and ganS-CMV infection (n = 109), matched by donor/recipient CMV serostatus, year and organ transplanted, and clinical manifestation. We used χ2 (categorical) and Mann-Whitney (continuous) tests to determine predisposing factors and morbidity attributable to resistance, and Kaplan-Meier plots to analyze survival differences.

Results: The rate of ganR-CMV was 1% (37/3467) overall and 4.1% (32/777) among CMV donor-positive, recipient-negative patients, and was stable over the study period. GanR-CMV was associated with increased prior exposure to ganciclovir (median, 153 vs 91 days, P < .001). Eighteen percent (3/17) of lung transplant recipients with ganR-CMV had received <6 weeks of prior ganciclovir (current guideline-recommended resistance testing threshold), and all non-lung recipients had received ≥90 days (median, 160 [range, 90-284 days]) prior to diagnosis of ganR-CMV. GanR-CMV was associated with higher mortality (11% vs 1%, P = .004), fewer days alive and nonhospitalized (73 vs 81, P = .039), and decreased renal function (42% vs 19%, P = .008) by 3 months after diagnosis.

Conclusions: GanR-CMV is associated with longer prior antiviral duration and higher attributable morbidity and mortality than ganS-CMV. Upcoming revised CMV guidelines should incorporate organ transplant-specific thresholds of prior drug exposure to guide rational ganR-CMV testing in SOT recipients. Improved strategies for prevention and treatment of ganR-CMV are warranted.

Keywords: cytomegalovirus; ganciclovir resistance; outcomes; risk factors; solid organ transplant.

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Figures

Figure 1.
Figure 1.
Kaplan-Meier curve of survival following cytomegalovirus (CMV) diagnosis in transplant recipients with ganciclovir-resistant (GanR) CMV and ganciclovir-sensitive (GanS) CMV.
See this image and copyright information in PMC

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