Author:
|
López Aladid, Rubén; Guiu, Alba; Sanclemente, Gemma; López Medrano, Francisco; Cofán Pujol, Federico; Mosquera, Maria Mar; Torre-Cisneros, Julián; Vidal, Elisa; Moreno Camacho, Ma. Asunción; Aguado, José María; Cordero, Elisa; Martin Gandul, Cecilia; Pérez Romero, Pilar; Carratalà, Jordi; Sabé, Nuria; Niubó, Jordi; Cervera, Carlos; Cervilla, Anna; Bodro, Marta; Muñoz, Patricia; Fariñas, María Carmen; Codina, M. Gemma; Aranzamendi, Maitane; Montejo, Miguel; Len, Oscar; Marcos Maeso, Ma. Angeles
|
Abstract:
|
BACKGROUND: Current guidelines recommend that treatment of
resistant cytomegalovirus (CMV) in solid organ transplant (SOT)
recipients must be based on genotypic analysis. However, this
recommendation is not systematically followed. OBJECTIVES: To
assess the presence of mutations associated with CMV resistance
in SOT recipients with suspected resistance, their associated
risk factors and the clinical impact of resistance. STUDY
DESIGN: Using Sanger sequencing we prospectively assessed the
presence of resistance mutations in a nation-wide prospective
study between September 2013-August 2015. RESULTS: Of 39
patients studied, 9 (23%) showed resistance mutations. All had
one mutation in the UL 97 gene and two also had one mutation in
the UL54 gene. Resistance mutations were more frequent in lung
transplant recipients (44% p=0.0068) and in patients receiving
prophylaxis >/=6 months (57% vs. 17%, p=0.0180). The mean
time between transplantation and suspicion of resistance was
longer in patients with mutations (239 vs. 100days,
respectively, p=0.0046) as was the median treatment duration
before suspicion (45 vs. 16days, p=0.0081). There were no
significant differences according to the treatment strategies or
the mean CMV load at the time of suspicion. Of note,
resistance-associated mutations appeared in one patient during
CMV prophylaxis and also in a seropositive organ recipient.
Incomplete suppression of CMV was more frequent in patients with
confirmed resistance. CONCLUSIONS: Our study confirms the need
to assess CMV resistance mutations in any patient with criteria
of suspected clinical resistance. Early confirmation of the
presence of resistance mutations is essential to optimize the
management of these patients. |