title: Increased risk of breakthrough infection among cytomegalovirus donor-positive/recipient-negative kidney transplant recipients receiving lower-dose valganciclovir prophylaxis.
abstract: OBJECTIVE
  We compared the effectiveness of lower-dose (LD) (450 mg/day for 6 months) to standard-dose (SD) (900 mg/day for 6 months) valganciclovir (VGCV) prophylaxis for prevention of cytomegalovirus (CMV) infection and disease in high-risk CMV donor-positive/recipient-negative (D+/R-) kidney recipients.
  
  
  METHODS
  We performed a single-center, retrospective cohort study, in a 750-bed academic medical center, involving a total of 90 evaluable CMV high-risk kidney recipients. All patients were retrospectively followed from day of transplantation to November 1, 2012, or to the development of CMV infection or disease, death, or loss to follow-up. CMV screening was only done if suggestive symptoms or abnormal laboratory values were present. Our immunosuppressive protocol otherwise did not differ between periods.
  
  
  RESULTS
  In total, 45 consecutive eligible patients initiated SD prophylaxis in the 22 months before the institutional protocol change regarding CMV prophylaxis. One patient developed CMV infection in the setting of non-adherence. In the 16 months after the protocol update, 45 consecutive eligible patients receiving LD prophylaxis were evaluated: 6 developed CMV infection while receiving prophylaxis (P = 0.11). Ganciclovir (GCV)-resistant infection was confirmed in 1 patient in the LD prophylaxis group. Late-onset CMV infection or disease occurred in 11 patients (24%) in the SD group and in 12 patients (27%) in the LD group (P = 0.86). More patients in the SD group developed leukopenia (75% vs. 44%, P < 0.01). During the study period, no significant differences were seen between the groups in mean mg/kg exposure to rabbit anti-thymocyte globulin induction courses, mean tacrolimus troughs, number of rejection episodes, mean estimated renal function, graft survival, or patient survival. Overall mean follow-up (± standard deviation) was 357 days (± 53) in the SD group and 320 days (± 103) in the LD group (P = 0.03).
  
  
  CONCLUSIONS
  Breakthrough CMV infection while receiving VGCV prophylaxis occurred more often after the institutional protocol revision to LD VGCV prophylaxis. Given our concern for increased risk of breakthrough infection and GCV resistance when prophylaxis is under-dosed, our institutional protocols were revised back to SD prophylaxis for all CMV D+/R- kidney transplant recipients.
authors: Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: D R
authors: DR
authors: Stevens
authors: D
authors: D
authors: Sawinski
authors: E
authors: E
authors: Blumberg
authors: N
authors: N
authors: Galanakis
authors: R D
authors: RD
authors: Bloom
authors: J
authors: J
authors: Trofe-Clark
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D064591:Allografts / Q000821:virology*; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: cytomegalovirus; ganciclovir; infection; prophylaxis; renal transplant; valganciclovir