Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients.

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).

Conclusion: 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.