title: Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5-10% of CMV-infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown.
  
  
  METHODS
  A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV-infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection.
  
  
  RESULTS
  During the 16-month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV-infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV-resistant (GCV-R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV-R CMV infection (P = 0.01).
  
  
  CONCLUSIONS
  In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV-R CMV infection. In contrast, GCV levels were therapeutic in CMV-infected patients with delayed GCV response.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Gagermeier
authors.forename: J D
authors.initials: JD
authors.lastname: Rusinak
authors.forename: N S
authors.initials: NS
authors.lastname: Lurain
authors.forename: C G
authors.initials: CG
authors.lastname: Alex
authors.forename: D F
authors.initials: DF
authors.lastname: Dilling
authors.forename: C H
authors.initials: CH
authors.lastname: Wigfield
authors.forename: R B
authors.initials: RB
authors.lastname: Love
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir
keywords: cytomegalovirus; ganciclovir resistance; lung transplantation