Drug-resistant cytomegalovirus infection after lung transplantation: Incidence, characteristics, and clinical outcomes

J Heart Lung Transplant. 2019 Dec;38(12):1268-1274. doi: 10.1016/j.healun.2019.09.005. Epub 2019 Sep 10.

Abstract

Background: Cytomegalovirus (CMV) infection and development of CMV drug resistance can cause significant morbidity and mortality in patients with lung transplantation (LTX). We investigated the incidence of CMV drug resistance in adult patients with LTX and characterized this patient group and its outcomes.

Methods: We analyzed a single-center retrospective cohort of 735 patients who received LTX between January 2012 and October 2017. We assessed the incidences of CMV UL97 and UL54 genotyping for clinically suspected drug resistance and confirmed drug resistance. Case-matched controls (3 control patients for each resistant patient) were identified by matching for CMV serological status, development of CMV disease or significant viremia (≥3,000 IU/ml), and transplantation date.

Results: The incidence of drug-resistant CMV was 1.98% (11/556) in donor and/or recipient CMV-positive patients and 4.7% (7/150) in donor-positive/recipient-negative patients. Altogether, 27 patients were tested for drug resistance, and 11 strains were resistant, 8 sensitive, and 8 inconclusive. No differences in immunosuppression, acute rejection, or pre-transplant sensitization were seen between case-matched groups. The peak CMV viral load and mean duration of viremia were significantly higher in the resistant group (324,000 vs. 117,000 mean IU/ml, p = 0.048 and 140 vs. 55 days, p < 0.001, respectively). The resistant group had increased overall mortality after onset of viremia compared with controls (3-year mortality 70% vs. 30%; p = 0.01).

Conclusions: Drug-resistant CMV infection is rare, but patients who develop it have decreased overall survival. Peak CMV viral load and duration of CMV viremia were associated with development of resistant CMV infection.

Keywords: CMV disease; cytomegalovirus; ganciclovir resistance; infectious diseases; lung transplantation.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / epidemiology*
  • Drug Resistance, Viral*
  • Female
  • Humans
  • Incidence
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Postoperative Complications / diagnosis
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / virology
  • Retrospective Studies
  • Treatment Outcome