A single-center experience with ganciclovir-resistant cytomegalovirus in lung transplant recipients: treatment and outcome

J Heart Lung Transplant. 2007 Dec;26(12):1286-92. doi: 10.1016/j.healun.2007.09.012. Epub 2007 Nov 19.

Abstract

Background: Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality after lung transplantation despite ganciclovir prophylaxis. The emergence of ganciclovir-resistant CMV in lung transplant patients has been reported, although the optimal strategy for the management of these infections remains uncertain. A review of the results of glanciclovir susceptibility testing in lung transplant recipients was performed.

Methods: We found 54% (113 of 210) of lung transplant patients developed CMV infection over a 4-year study period with ganciclovir-resistant CMV infection occurring in >5% of patients (6 of 113). The demographic and clinical characteristics of patients who developed ganciclovir-resistant vs -sensitive CMV infection were similar, although 50% (3 of 6) patients who developed resistance were CMV mismatched (D(+)/R(-) serology). All patients' CMV isolates had mutations in the UL97 gene. In addition, the 3 mismatch patients also had CMV with mutations in the UL54 gene.

Results: Treatment with a combination of foscarnet and ganciclovir or foscarnet alone for ganciclovir-resistant infection led to a significant reduction in virologic load in all patients (p = 0.03), although transient increases in viremia were observed in some patients early after treatment. Renal function worsened after treatment, but overall it was not significantly different from pre-treatment values (p = 0.07).

Conclusions: Single or combination therapy with foscarnet is effective for treatment of ganciclovir-resistant isolates and excessive concern regarding toxicity should not preclude consideration of these treatments when clinically indicated.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Cytomegalovirus / genetics
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / etiology
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • Foscarnet / therapeutic use*
  • Ganciclovir / therapeutic use*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Opportunistic Infections / drug therapy*
  • Opportunistic Infections / etiology
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Postoperative Complications*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Foscarnet
  • Phosphotransferases (Alcohol Group Acceptor)
  • ganciclovir kinase
  • Ganciclovir