A single-center experience with ganciclovir-resistant cytomegalovirus in lung transplant recipients: treatment and outcome.
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.
Reddy
Anita J
AJ
Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA. reddya3@ccf.org
Zaas
Aimee K
AK
Hanson
Kimberly E
KE
Palmer
Scott M
SM
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000209:etiology; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use*; D015774:Ganciclovir / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009894:Opportunistic Infections / Q000188:drug therapy* / Q000209:etiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011183:Postoperative Complications; D012189:Retrospective Studies; D016896:Treatment Outcome
D000998:Antiviral Agents; D017245:Foscarnet; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D015774:Ganciclovir