Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection.
BACKGROUND
Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients.


OBJECTIVE
To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center.


METHODS
Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data.


RESULTS
Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis.


CONCLUSIONS
GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.
Isada
C M
CM
Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Yen-Lieberman
B
B
Lurain
N S
NS
Schilz
R
R
Kohn
D
D
Longworth
D L
DL
Taege
A J
AJ
Mossad
S B
SB
Maurer
J
J
Flechner
S M
SM
Mawhorter
S D
SD
Braun
W
W
Gordon
S M
SM
Schmitt
S K
SK
Goldman
M
M
Long
J
J
Haug
M
M
Avery
R K
RK
D003587:Cytomegalovirus / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000517:prevention & control* / Q000628:therapy; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D017245:Foscarnet / Q000494:pharmacology / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*
D017245:Foscarnet; D015774:Ganciclovir