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

Year 2016, Volume: 1 Issue: 3, 53 - 57, 30.12.2016

Ajda Turhan

https://doi.org/10.5455/jicm.12.2016070

Cited By: 1

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., Illınois, 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.

Keywords

Cytomegalovirus, ganciclovir resistance, mutation, UL97

References

• Humar A, Snydman D. Cytomegalovirus in solid organ transplant recipients. Am J Transplant 2009; 9: 78-86.
• Limaye AP, Corey L, Koelle DM, Davis CL, Boeckh M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet 2000; 356: 645-649.
• Lurain NS, Bhorade SM, Pursell KJ, Avery RK, Yeldandi VV, Isada CM, et al. Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients. J Infect Dis 2002; 186:760-768.
• Marfori JE, Exner MM, Marousek GI, Chou S, Drew WL. Development of new cytomegalovirus UL97 and DNA polymerase mutations conferring drug resistance after valganciclovir therapy in allogeneic stem cell recipients. J Clin Virol 2007; 38: 120-125.
• Torres-Madriz G, Boucher HW. Immunocompromised hosts: perspectives in the treatment and prophylaxis of cytomegalovirus disease in solid-organ transplant recipients. Clin Infect Dis 2008; 47: 702-711.
• Limaye AP, Raghu G, Koelle DM, Ferrenberg J, Huang ML, Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis 2002; 185: 20-27.
• Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev 2010; 23: 689-712.
• Eckle T, Lang P, Prix L, Jahn G, Klingebiel T, Handgretinger R, et al. Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant 2002; 30: 433-439.
• Wolf DG, Yaniv I, Honigman A, Kassis I, Schonfeld T, Ashkenazi S. Early emergence of ganciclovir-resistant human cytomegalovirus strains in children with primary combined immunodeficiency. J Infect Dis 1998; 178: 535-538.
• Castor J, Cook L, Corey L, Jerome KR. Rapid detection directly from patient serum samples of human cytomegalovirus UL97 mutations conferring ganciclovir resistance. J Clin Microbiol 2007; 45: 2681-2683.
• Chou S, Waldemer RH, Senters AE, Michels KS, Kemble GW, Miner RC, Drew WL. Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir. J Infect Dis 2002; 185: 162-169.
• Opelz G, Dohler B, Ruhenstroth A. Cytomegalovirus prophylaxis and graft outcome in solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004; 4: 928-936.
• Erice A. Resistance of human cytomegalovirus to antiviral drugs. Clin Microbiol Rev 1999; 12: 286-297.
• Emery VC, Griffiths PD. Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy. Proc Natl Acad Sci USA 2000; 97: 8039-8044.
• Bueno J, Ramil C, Green M. Current management strategies for the prevention and treatment of cytomegalovirus infection in pediatric transplant recipients. Paediatr Drugs 2002; 4: 279-290.
• Eckle T, Prix L, Jahn G, Klingebiel T, Handgretinger R, Selle B, Hamprecht K. Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood 2000; 96: 3286-3289.
• Hantz S, Garnier-Geoffroy F, Mazeron MC, Garrigue I, Merville P, Mengelle C, et al. Drug-resistant cytomegalovirus in transplant recipients: a French cohort study. J Antimicrob Chemother 2010; 65: 2628-2640.
• Boutolleau D, Deback C, Bressollette-Bodin C, Varnous S, Dhedin N, Barrou B, et al. Resistance pattern of cytomegalovirus (CMV) after oral valganciclovir therapy in transplant recipients at high-risk for CMV infection. Antiviral Res 2009; 81: 174-179.