title: Risk Factors and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infection in Solid Organ Transplant Recipients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Fisher
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.
authors.forename: Janine L
authors.initials: JL
authors.lastname: Knudsen
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.|Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Erika D
authors.initials: ED
authors.lastname: Lease
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.|Virology Division, Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Rakita
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.|Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.affiliation: Division of Allergy and Infectious Diseases, University of Washington.
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D012189:Retrospective Studies; D012307:Risk Factors; D066027:Transplant Recipients / Q000706:statistics & numerical data*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir
keywords: cytomegalovirus; ganciclovir resistance; outcomes; risk factors; solid organ transplant