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The first two ganciclovir resistant cytomegalovirus isolates from kidney and pediatric stem cell transplant recipients in Turkey

Aysinn Zeytinoglu; Ajda Turhan; Ahmet Keskinoglu; Serap Aksoylar; Nida Dincel; Burcu Deveci; Ergul Utkun; Sevgi Mir.

Abstract
Background: The emergence of cytomegalovirus (CMV) resistance to antivirals causes an increasing problem in transplant recipients, complicating therapeutic and clinical management. Widely used antivirals for therapy, preemptive therapy, and prophylaxis are the causes for resistance. This study aimed to report the first two transplant recipients who had CMV ganciclovir (GCV) resistance assessed by UL97 viral gene sequencing in Turkey.
Case presentation: CMV infection was monitored by plasma quantitative viral DNA real-time polymerase chain reaction (Abbott Molecular Inc., Illýnois, USA) in the transplant recipients. Sequence analysis of CMV UL97 in CMV DNA–positive cases for GCV resistance was conducted, and while looking for UL97 GCV resistance in Ege University hospital, the first renal transplantation recipient with CMV mutation in Turkey was detected. Also, a stem cell transplant recipient was the first case for pediatric stem cell transplantation having UL97 GCV-resistant strain in Turkey. A594V and C603W mutations were the detected mutations, respectively.
Conclusion: Using GCV/valganciclovir (VGCV) for preemptive therapy, prophylaxis, treatment, and especially maintenance therapy for a long time with VGCV when CMV DNA is still detectable in peripheral blood might represent a risk factor for the emergence of CMV GCV resistance. The present findings indicate that resistance to widely used GCV as therapy, preemptive therapy, and prophylaxis should be monitored carefully in transplant recipients routinely for good patient management and effective antiviral therapy.

Key words: Cytomegalovirus;ganciclovir resistance;mutation;UL97


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