Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients.
BACKGROUND
Since ganciclovir-resistant cytomegalovirus (CMV) disease was initially described in a patient with acquired immunodeficiency syndrome (AIDS) in 1986, the incidence of ganciclovir-resistant CMV disease appears to be increasing in immunocompromised patients. More recently, there have been sporadic reports of ganciclovir-resistant CMV disease in solid organ transplantation.


METHODS
We retrospectively assessed the incidence of ganciclovir-resistant CMV disease in all lung transplant recipients transplanted between 6/93 and 6/01 at Loyola University Medical Center. All patients underwent routine CMV blood culture, shell vial assay as well as phenotypic and genotypic anti-viral susceptibility testing according to a pre-determined schedule. The number of CMV episodes, intravenous ganciclovir use, acute and chronic rejection and survival data were documented for all patients.


RESULTS
Twelve of 212 (6%) transplant recipients developed ganciclovir-resistant CMV disease. Ganciclovir resistance was associated with a higher number of CMV episodes (3.4 +/- 2.3 episodes/patient vs 1.7 +/- 0.7 episodes/patient [p < 0.05]) and an increased exposure to cumulative intravenous ganciclovir in the primary CMV-mismatched (D(+)R(-)) population (22 +/- 10 vs 13 +/- 7 days [p < 0.05]) compared with patients who did not develop ganciclovir resistance. In addition, the use of daclizumab therapy was associated with a 7-fold greater likelihood of developing ganciclovir resistance (p < 0.0001). The presence of ganciclovir-resistant CMV disease in our population was associated with a decreased survival that could be attributed to CMV disease itself (p < 0.05).


CONCLUSIONS
By screening all lung transplant recipients with CMV disease for ganciclovir resistance, we were able to detect a higher incidence of ganciclovir-resistant CMV disease (6%) than previously seen in solid organ transplantation. High-risk patients (D(+)R(-) CMV serostatus) who receive anti-lymphocytic therapy should be monitored aggressively and treated to prevent the development of ganciclovir resistance and avert a negative outcome.
Bhorade
Sangeeta M
SM
Lung Transplant Program, Division of Pulmonary Medicine, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
Lurain
Nell S
NS
Jordan
Ashby
A
Leischner
Julie
J
Villanueva
Jaime
J
Durazo
Ramon
R
Creech
Steve
S
Vigneswaran
Wickii T
WT
Garrity
Edward R
ER
D000328:Adult; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000187:drug effects* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D004279:DNA, Viral / Q000032:analysis; D004352:Drug Resistance, Microbial; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000627:therapeutic use*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000453:epidemiology / Q000821:virology*; D011336:Probability; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D018709:Statistics, Nonparametric; D015996:Survival Rate; D014181:Transplantation Immunology / Q000502:physiology
D004279:DNA, Viral; D015774:Ganciclovir