Cytomegalovirus Infection and Rates of Antiviral Resistance Following Intestinal and Multivisceral Transplantation.
BACKGROUND
Cytomegalovirus (CMV) disease is a common and clinically significant complication following intestinal or multivisceral transplantation. CMV disease is more common in cases of serologic mismatch between donor and recipient. Though in some cases it may be asymptomatic, in the immunosuppressed population it often manifests with evidence of systemic infection or end-organ disease.


METHODS
We conducted a retrospective review of all patients undergoing intestinal or multivisceral transplantation over 8 years at our institution.


RESULTS
Forty-eight transplantations were performed, with 40% of the patients (19/48) having ≥1 episode of CMV viremia, which rose to 90% in the "donor-positive, recipient-negative" (DPRN) serologic mismatch group. The median time to 1st episode following transplantation was 22.3 weeks (range, 1-78) and median duration of each episode was 4.9 weeks (range, 1.6-37.4). Six of the 19 viremic patients (31.6%) developed virologic resistance with 4 of these occurring in the DPRN group. Four of the 6 patients with drug-resistant CMV died with CMV viremia. All patients with drug resistance acquired ganciclovir resistance; these patients were more challenging to manage with second-line toxicity-limited treatments, including foscarnet, cidofovir, and leflunomide. CMV immunoglobulin has been used and we briefly discuss the use of CMV-specific adoptive T-lymphocyte transfer in the management of 1 case.


CONCLUSIONS
Post-transplantation CMV disease continues to be challenging to manage, and there is little consensus on optimal management strategies in this patient group, with a significant requirement for novel therapies; these may be pharmacologic or cell based. Extensive multidisciplinary discussion is important for most cases, but particularly for those patients who acquire virologic resistance.
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
T
T
Ambrose
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
L M
LM
Sharkey
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
J
J
Louis-Auguste
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
C S
CS
Rutter
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
S
S
Duncan
Department of Clinical Virology, Addenbrooke's Hospital, Cambridge, United Kingdom.
S
S
English
Department of Infectious Diseases, Addenbrooke's Hospital, Cambridge, United Kingdom.
E
E
Gkrania-Klotsas
Department of Infectious Diseases, Addenbrooke's Hospital, Cambridge, United Kingdom.
A
A
Carmichael
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
J M
JM
Woodward
Department of Transplant Surgery, Addenbrooke's Hospital, Cambridge, United Kingdom.
N
N
Russell
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom.
D
D
Massey
Department of Transplant Surgery, Addenbrooke's Hospital, Cambridge, United Kingdom.
A
A
Butler
Department of Gastroenterology, Addenbrooke's Hospital, Cambridge, United Kingdom. Electronic address: stephen.middleton@addenbrookes.nhs.uk.
S
S
Middleton
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology*; D024882:Drug Resistance, Viral; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007422:Intestines / Q000637:transplantation*; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014766:Viremia / Q000188:drug therapy / Q000453:epidemiology*
D000998:Antiviral Agents; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007555:Isoxazoles; C045781:cytomegalovirus-specific hyperimmune globulin; D017245:Foscarnet; D000077339:Leflunomide; D015774:Ganciclovir