Management of Multidrug-Resistant CMV Infection in Immunocompromised Patients: Case Report of a Heart-Transplant Recipient and Review of the Literature
Free accessCase reportFirst published online February, 2015
Management of Multidrug-Resistant CMV Infection in Immunocompromised Patients: Case Report of a Heart-Transplant Recipient and Review of the Literature
Cytomegalovirus (CMV) remains a leading cause of morbidity after solid organ transplantation. The efficiency of antivirals for the treatment of CMV infections may be hampered because of the emergence of CMV resistance to antivirals. The development of CMV multidrug resistance, which remains uncommon but does occur, constitutes a clinically challenging complication and may contribute to difficult therapeutic management and adverse clinical outcome. We report here the observation of the emergence of a multidrug-resistant CMV infection in a heart-transplant recipient and review the literature on similar cases to identify the potential strategies for the successful management of CMV multidrug resistance among immunocompromised patients.
References
1.
LurainN.S., ChouS.Antiviral drug resistance of human cytomegalovirus.Clin Microbiol Rev2010; 23: 689–712.
2.
KottonC.N., KumarD., CaliendoA.M.Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation.Transplantation2013; 96: 333–360.
3.
DebackC., FilletA.M., DhedinN.Monitoring of human cytomegalovirus infection in immunosuppressed patients using real-time PCR on whole blood.J Clin Virol2007; 40: 173–179.
4.
BoutolleauD., DebackC., Bressollette-BodinC.Resistance pattern of cytomegalovirus (CMV) after oral valganciclovir therapy in transplant recipients at high-risk for CMV infection.Antiviral Res2009; 81: 174–179.
5.
SacreK., NguyenS., DebackC.Expansion of human cytomegalovirus (HCMV) immediate-early 1-specific CD8+ T cells and control of HCMV replication after allogeneic stem cell transplantation.J Virol2008; 82: 10143–10152.
6.
LiF., KenyonK.W., KirbyK.A., FishbeinD.P., BoeckhM., LimayeA.P.Incidence and clinical features of ganciclovir-resistant cytomegalovirus disease in heart transplant recipients.Clin Infect Dis2007; 45: 439–447.
7.
IwasenkoJ.M., ScottG.M., NaingZ., GlanvilleA.R., RawlinsonW.D.Diversity of antiviral-resistant human cytomegalovirus in heart and lung transplant recipients.Transpl Infect Dis2011; 13: 145–153.
8.
BlackmanS.C., LurainN.S., WitteD.P., FilipovichA.H., GroenP., SchleissM.R.Emergence and compartmentalization of fatal multi-drug-resistant cytomegalovirus infection in a patient with autosomal-recessive severe combined immune deficiency.J Pediatr Hematol Oncol2004; 26: 601–605.
9.
ChouS., MarousekG., GuentzelS.Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease.J Infect Dis1997; 176: 786–789.
10.
ChouS., MinerR.C., DrewW.L.A deletion mutation in region V of the cytomegalovirus DNA polymerase sequence confers multidrug resistance.J Infect Dis2000; 182: 1765–1768.
11.
GoldsmithP.M., HusainM.M., CarmichaelA., ZhangH., MiddletonS.J.Case-report: Multidrug-resistant cytomegalovirus in a modified multivisceral transplant recipient.Transplantation2012; 93: e30–e32.
12.
HantzS., Garnier-GeoffroyF., MazeronM.C.Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.J Antimicrob Chemother2010; 65: 2628–2640.
13.
KaulD.R., StoelbenS., CoberE.First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246.Am J Transplant2011; 11: 1079–1084.
14.
LeviM.E., MandavaN., ChanL.K., WeinbergA., OlsonJ.L.Treatment of multidrug-resistant cytomegalovirus retinitis with systematically administered leflunomide.Transpl Infect Dis2006; 8: 38–43.
15.
StrasfeldL., LeeI., TatarowiczW., VillanoS., ChouS.Virologic characterization of multidrug-resistant cytomegalovirus infection in 2 transplant recipients treated with maribavir.J Infect Dis2010; 202: 104–108.
16.
DunnJ.H., WeinbergA., ChanL.K., MandavaN., LeviM.E., OlsonJ.L.Long-term suppression of multi-drug-resistant cytomegalovirus retinitis with systemically administered leflunomide.JAMA Ophthalmol2013; 131: 958–960.
17.
VerkaikN.J., HoekR.A., van BergeijikH.Leflunomide as part of the treatment for multi-drug-resistant cytomegalovirus disease after lung transplantation: case report and review of the literature.Transpl Infect Dis2013; 15: E243–E249.
18.
GermiR., MarietteC., AlainS.Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus.Antiviral Res2014; 101: 57–61.
19.
EmeryV.C., SabinC.A., CopeA.V., GorD., Hassan-WalkerA.F., GriffithsP.D.Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation.Lancet2000; 355: 2032–2036.
20.
AveryR.K.Update in management of ganciclovir-resistant cytomegalovirus infection.Curr Opin Infect Dis2008; 21: 433–437.
21.
AveryR.K., MossadS.B., PoggioE.Utility of leflunomide in the treatment of complex cytomegalovirus syndromes.Transplantation2010; 90: 419–426.
22.
BrennanD.C., LegendreC., PatelD.Cytomegalovirus incidence between everolimus versus mycophenolate in de novo renal transplants: pooled analysis of three clinical trials.Am J Transplant2011; 11: 2453–2462.
23.
GoldnerT., HewlettG., EttischerN., Rubsamen-SchaeffH., ZimmermannH., LischkaP.The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.J Virol2011; 85: 10884–10893.
24.
BrennanD.C., AguadoJ.M., PotenaL.Effect of maintenance immunosuppressive drugs on virus pathobiology: evidence and potential mechanisms.Rev Med Virol2013; 23: 97–125.
25.
SabéN., Gonzalez-CostelloJ., RamaI.Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.Transpl Int2012; 25: e78–e82.
