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CMV disease resistant to Ganciclovir. Should valganciclovir plasma levels be monitored in high risk patients?
Enfermedad por CMV resistente a ganciclovir ¿Está indicado monitorizar niveles plasmáticos de valganciclovir en pacientes de alto riesgo ?
EUGENIA SOLAa, ENCARNACION VEGAa, CRISTINA GUTIERREZa, VERONICA LOPEZa, MERCEDES CABELLOa, DOLORES BURGOSa, MIGUEL GONZALEZ MOLINAa, JUAN SILESa
a SERVICIO DE NEFROLOGIA, HOSPITAL CARLOS HAYA, MALAGA, MALAGA, ESPAÑA,
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    "textoCompleto" => "<p class="elsevierStylePara">Dear Editor&#44;</p><p class="elsevierStylePara">We report the case of a patient who received a kidney transplant in June 2007&#46; The donor was Ig G CMV positive and the recipient was negative&#46; The immunosuppression consisted of steroids&#44; mycophenolate &#40;1g&#47;day&#41; and tacrolimus &#40;0&#46;1mg&#47;12 h&#41;&#46; Borderline&#47;acute rejection occurred on the 11th day post-transplant and was successfully treated with steroids&#46;</p><p class="elsevierStylePara">The patient was discharged with good renal function&#44; Cr 0&#46;9mg&#47;dl on prophylactic treatment with valganciclovir&#44; for six months having to repeatedly adjust the doses because of leucopenia&#46; CMV viral load was negative whilst on treatment&#46;</p><p class="elsevierStylePara">10 days after discontinuing treatment&#44; the patient presented with diarrhoea&#44; abdominal pain&#44; fever&#44; leucopenia and thrombocytopenia&#44; and deterioration of renal function&#44; blood and urine cultures were negative and CMV- PCR was positive&#44; 101&#44;000 copies&#47;ml&#46;</p><p class="elsevierStylePara">Treatment was started with valganciclovir and the dose of MMF was reduced&#46; The fever subsided and the CMV viral load began to decrease&#46;</p><p class="elsevierStylePara">The patient was discharged with stable kidney function &#40;1mg&#47;dl&#41;&#44; without leucopenia and on treatment with valganciclovir&#46;</p><p class="elsevierStylePara">A few days later&#44; the patient presented with low fever&#44; abdominal pain and persistent CMV viral load &#40;4&#44;900cop&#47;ml&#41;&#46; The patient received treatment with intravenous ganciclovir during 20 days until the CMV viral load was negative in blood&#46; The patient was discharged without symptoms&#44; with normal leucocyte count and on valganciclovir treatment&#46;</p><p class="elsevierStylePara">Three days after discharge&#44; the patient developed fever&#44; epigastrium pain and leucopenia again&#46; CMV- PCR was negative in blood&#46; Screening for acute febrile illness was negative except for discreet hepatosplenomegaly&#46; The upper endoscopy showed normal mucosa of which biopsies were taken&#46; The qualitative PCR of the gastric tissue was positive for CMVand HSV 6&#46; Intravenous gancyclovir was reinitiated&#46; Non-specific abdominal pain persisted along with anaemia and leucopenia&#44; needing treatment with granulocyte colony-stimulating factor&#44; transfusion of erythrocyte concentrate&#46; The patient continued to have low-grade fever&#46; The CMV serum PCR remained negative&#46;</p><p class="elsevierStylePara">Suspecting CMV disease resistant to ganciclovir&#44; a drug resistance test was carried out on the gastric specimen&#46; An L 595F mutation in UL97 was found&#46;</p><p class="elsevierStylePara">The UL97 gene regulates the phosphorylation of the ganciclovir associated with resistance to it&#46; We then began treatment with intravenous foscarnet and specific anti-CMV immunoglobulin 200mg&#47;kg every three weeks&#46; The patient became asymptomatic after 10 days of treatment with normal leukocyte count&#46; The complications of this treatment included transient acute kidney failure at two weeks&#44; with hypomagnesaemia and hypokalaemia&#46;</p><p class="elsevierStylePara">The treatment continued for one month&#44; followed by valganciclovir and foscarnet every 48 hours until the therapeutic levels of valganclovir were confirmed&#46; Since then&#44; the patient has remained asymptomatic and with excellent kidney function&#44; six months after the episode&#46;</p><p class="elsevierStylePara">The difficulty in diagnosing CMV Diease in this case was because of the false negative CMV viral load test requiring the confirmation of CMV and its resistance on gastric tissue&#46; The resistance of the treatment was probably enhanced by inadequate doses of valganciclovir&#44; which stresses the importance of monitoring vanganciclovir levels to ensure an adequate treatment thus avoiding the development of resistance to the treatment&#46;</p>"
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Article information
ISSN: 20132514
Original language: English
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