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器官移植后巨细胞病毒耐药的处理

康一生 于立新

康一生, 于立新. 器官移植后巨细胞病毒耐药的处理[J]. 器官移植, 2017, 8(1): 73-77. doi: 10.3969/j.issn.1674-7445.2017.01.014
引用本文: 康一生, 于立新. 器官移植后巨细胞病毒耐药的处理[J]. 器官移植, 2017, 8(1): 73-77. doi: 10.3969/j.issn.1674-7445.2017.01.014

器官移植后巨细胞病毒耐药的处理

doi: 10.3969/j.issn.1674-7445.2017.01.014
详细信息
    通讯作者:

    于立新,Email:fiyiak@yeah.net

  • 中图分类号: R617, R511

  • 摘要: 巨细胞病毒(CMV)感染是器官移植术后常见的并发症,其耐药发生亦非罕见,且易导致临床预后不良。CMV耐药的危险因素来源于宿主、病毒以及抗病毒药物等各个方面,产生耐药的原因则主要由于药物发挥活性的基因(UL97基因)或病毒复制的基因(UL54基因)发生突变所致。目前临床上诊断CMV耐药的手段相对缺乏,主要依靠检测病毒基因突变,并以此指导下一步的临床决策。UL97基因突变的临床措施可以将更昔洛韦更换为西多福韦或膦甲酸钠,而UL54基因突变则通常可以更换为膦甲酸钠。目前一些新型抗CMV药物如letermovir、maribavir、brincidofovir以及一些用于其他指征的药物如来氟米特、青蒿酯也为CMV耐药的治疗带来了新的曙光。

     

  • [1] Beam E, Razonable RR. Cytomegalovirus in solid organ transplantation: epidemiology, prevention, and treatment[J]. Curr Infect Dis Rep, 2012, 14(6): 633-641. DOI: 10.1007/s11908-012-0292-2.
    [2] Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004[J]. Clin Infect Dis, 2010, 50(11): 1439-1447. DOI: 10.1086/652438.
    [3] Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection[J]. Rev Med Virol, 2010, 20(4): 202-213. DOI: 10.1002/rmv.655.
    [4] Torre-Cisneros J, Aguado JM, Caston JJ, et al. Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations[J]. Transplant Rev, 2016, 30(3): 119-143. DOI: 10.1016/j.trre.2016.04.001.
    [5] Razonable R. Direct and indirect effects of cytomegalovirus:can we prevent them?[J]. Enferm Infecc Microbiol Clin, 2010, 28(1): 1-5. DOI: 10.1016/j.eimc.2009.07.008.
    [6] Arthurs SK, Eid AJ, Deziel PJ, et al. The impact of invasive fungal diseases on survival after lung transplantation[J]. Clin Transplant, 2010, 24(3): 341-348. DOI: 0.1111/j.1399-0012.2009.01076.x.
    [7] Luscalov S, Loga L, Dican L, et al. Cytomegalovirus infection in immunosuppressed patients after kidney transplantation[J]. Clujul Med, 2016, 89(3): 343-346. DOI: 10.15386/cjmed-587.
    [8] Fehr T, Cippà PE, Mueller NJ. Cytomegalovirus post kidney transplantation: prophylaxis versus pre-emptive therapy?[J]. Transpl Int, 2015, 28(12): 1351-1356. DOI: 10.1111/tri.12629.
    [9] Kotton CN, Kumar D, Caliendo AM, et al. International consensus guidelines on the management of cytomegalovirus in solid organ transplantation[J]. Transplantation, 2010, 89(7): 779-795. DOI: 10.1097/TP.0b013e3181cee42f.
    [10] Santos CA. Cytomegalovirus and other β-Herpesviruses[J]. Semin Nephrol, 2016, 36(5): 351-361. DOI: 10.1016/j.semnephrol.2016.05.012.
    [11] Cameron BM, Kennedy SE, Rawlinson WD, et al. The efficacy of valganciclovir for prevention of infections with cytomegalovirus and Epstein-Barr virus after kidney transplant in children[J]. Pediatr Transplant, 2016, DOI: 10.1111/petr.12816[Epubaheadofprint].
    [12] Lautenschlager I, Loginov R, Mäkisalo H, et al. Prospective long-term study on primary CMV infections in adult liver transplant (D+/R-) patients after valganciclovir prophylaxis[J]. J Clin Virol, 2015, 71: 73-75. DOI: 10.1016/j.jcv.2015.08.009.
    [13] Plosa EJ, Esbenshade JC, Fuller MP, et al. Cytomegalovirus infection[J]. Pediatr Rev, 2012, 33(4): 156-163. DOI: 10.1542/pir.33-4-156.
    [14] Boeckh M. Complications, diagnosis, management, and prevention of CMV infections: current and future[J]. Hematology Am Soc Hematol Educ Program, 2011: 305-309. DOI: 10.1182/asheducation-2011.1.305.
    [15] Sellar RS, Peggs KS. Management of multidrug-resistant viruses in the immunocompromised host[J]. Br J Haematol, 2012, 156(5): 559-572. DOI: 10.1111/j.1365-2141.2011.08988.x.
    [16] Einsele H, Mielke S, Grigoleit GU. Diagnosis and treatment of cytomegalovirus 2013[J]. Curr Opin Hematol, 2014, 21(6): 470-475. DOI: 10.1097/MOH.0000000000000090.
    [17] Chou S. Approach to drug-resistant cytomegalovirus in transplant recipients[J]. Curr Opin Infect Dis, 2015, 28(4): 293-299. DOI: 10.1097/QCO.0000000000000170.
    [18] Hakki M, Chou S. The biology of cytomegalovirus drug resistance[J]. Curr Opin Infect Dis, 2011, 24(6): 605-611. DOI: 10.1097/QCO.0b013e32834cfb58.
    [19] Limaye AP. Ganciclovir-resistant cytomegalovirus in organ transplant recipients[J]. Clin Infect Dis, 2002, 35(7): 866-872. doi: 10.1086/cid.2002.35.issue-7
    [20] Myhre HA, Haug Dorenberg D, Kristiansen KI, et al. Incidence and outcomes of ganciclovir-resistant cytomegalovirus infections in 1244 kidney transplant recipients[J]. Transplantation, 2011, 92(2): 217-223. DOI: 10.1097/TP.0b013e31821fad25.
    [21] Couzi L, Helou S, Bachelet T, et al. High incidence of anticytomegalovirus drug resistance among D+R-kidney transplant recipients receiving preemptive therapy[J]. Am J Transplant, 2012, 12(1): 202-209. DOI: 10.1111/j.1600-6143.2011.03766.x.
    [22] Boivin G, Goyette N, Rollag H, et al. Cytomegalovirus resistance in solid organ transplant recipients treated with intravenous ganciclovir or oral valganciclovir[J]. Antivir Ther, 2009, 14(5): 697-704. https://www.researchgate.net/profile/Anders_Asberg/publication/26764329_Cytomegalovirus_resistance_in_solid_organ_transplant_recipients_treated_with_intravenous_ganciclovir_or_oral_valganciclovir/links/0912f50a1310c19769000000.pdf
    [23] Beam E, Dioverti V, Razonable RR. Emerging cytomegalovirus management strategies after solid organ transplantation: challenges and opportunities[J]. Curr Infect Dis Rep, 2014, 16(9): 419. DOI: 10.1007/s11908-014-0419-8.
    [24] Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation[J]. Drugs, 2010, 70(8): 965-981. DOI: 10.2165/10898540-000000000-00000.
    [25] Le Page AK, Jager MM, Iwasenko JM, et al. Clinical aspects of cytomegalovirus antiviral resistance in solid organ transplant recipients[J]. Clin Infect Dis, 2013, 56(7): 1018-1029. DOI: 10.1093/cid/cis1035.
    [26] Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation[J]. Transplantation, 2013, 96(4): 333-360. DOI: 10.1097/TP.0b013e31829df29d.
    [27] Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus[J]. Clin Microbiol Rev, 2010, 23(4): 689-712. DOI: 10.1128/CMR.00009-10.
    [28] Garrigue I, Moulinas R, Recordon-Pinson P, et al. Contribution of next generation sequencing to early detection of cytomegalovirus UL97 emerging mutants and viral subpopulations analysis in kidney transplant recipients[J]. J Clin Virol, 2016, 80: 74-81. DOI: 10.1016/j.jcv.2016.04.017.
    [29] Komatsu TE, Pikis A, Naeger LK, et al. Resistance of human cytomegalovirus to ganciclovir/valganciclovir: a comprehensive review of putative resistance pathways[J]. Antiviral Res, 2014, 101: 12-25. DOI: 10.1016/j.antiviral.2013.10.011.
    [30] Kleiboeker S, Nutt J, Schindel B, et al. Cytomegalovirus antiviral resistance: characterization of results from clinical specimens[J]. Transpl Infect Dis, 2014, 16(4): 561-567. DOI: 10.1111/tid.12241.
    [31] Chou S, Ercolani RJ, Marousek G, et al. Cytomegalovirus UL97 kinase catalytic domain mutations that confer multidrug resistance[J]. Antimicrob Agents Chemother, 2013, 57(7): 3375-3379. DOI: 10.1128/AAC.00511-13.
    [32] Drouot E, Piret J, Lebel MH, et al. Characterization of multiple cytomegalovirus drug resistance mutations detected in a hematopoietic stem cell transplant recipient by recombinant phenotyping[J]. J Clin Microbiol, 2014, 52(11): 4043-4046. DOI: 10.1128/JCM.02205-14.
    [33] Fischer L, Laib Sampaio K, Jahn G, et al. Generation and characterization of a GCV resistant HCMV UL97-mutation and a drug sensitive UL54-mutation[J]. Antiviral Res, 2013, 100(3): 575-577. DOI: 10.1016/j.antiviral.2013.09.026.
    [34] Komazin-Meredith G, Chou S, Prichard MN, et al. Human cytomegalovirus UL97 kinase is involved in the mechanism of action of methylenecyclopropane analogs with 6-ether and -thioether substitutions[J]. Antimicrob Agents Chemother, 2014, 58(1): 274-278. DOI: 10.1128/AAC.01726-13.
    [35] Zhang Y, Zhao Z, Sun J, et al. A new mutation in the human cytomegalovirus UL97 gene may confer ganciclovir resistance in Chinese kidney transplant recipients[J]. Arch Virol, 2013, 158(1): 247-250. DOI: 10.1007/s00705-012-1479-4.
    [36] Campos AB, Ribeiro J, Boutolleau D, et al. Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art[J]. Rev Med Virol, 2016, 26(3): 161-182. DOI: 10.1002/rmv.1873.
    [37] Bacigalupo A, Boyd A, Slipper J, et al. Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients[J]. Expert Rev Anti Infect Ther, 2012, 10(11): 1249-1264. DOI: 10.1586/eri.12.115.
    [38] Razonable RR. Antiviral drugs for viruses other than human immunodeficiency virus[J]. Mayo Clin Proc, 2011, 86(10): 1009-1026. DOI: 10.4065/mcp.2011.0309.
    [39] Boeckh M, Murphy WJ, Peggs KS. Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies[J]. Biol Blood Marrow Transplant, 2015, 21(1): 24-29. DOI: 10.1016/j.bbmt.2014.11.002.
    [40] Fusconi M, Grasso M, Greco A, et al. Recurrent respiratory papillomatosis by HPV : review of the literature and update on the use of cidofovir[J]. Acta Otorhinolaryngol Ital, 2014, 34(6): 375-381. http://emedicine.medscape.com/article/302648-overview
    [41] Lischka P, Hewlett G, Wunberg T, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246[J]. Antimicrob Agents Chemother, 2010, 54(3): 1290-1297. DOI: 10.1128/AAC.01596-09.
    [42] Price NB, Prichard MN. Progress in the development of new therapies for herpesvirus infections[J]. Curr Opin Virol, 2011, 1(6): 548-554. DOI: 10.1016/j.coviro.2011.10.015.
    [43] Kaul DR, Stoelben S, Cober E, et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246[J]. Am J Transplant, 2011, 11(5): 1079-1084. DOI: 10.1111/j.1600-6143.2011.03530.x.
    [44] Golder T, Hewlett G, Ettischer N, et al. The novel anticytomegalovirus compound AIC246 (letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase[J]. J Virol, 2011, 85(20): 10884-10893. DOI: 10.1128/JVI.05265-11.
    [45] Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation[J]. N Engl J Med, 2013, 369(13): 1227-1236. DOI: 10.1056/NEJMoa1303688.
    [46] Marty FM, Ljungman P, Papanicolaou GA, et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial[J]. Lancet Infect Dis, 2011, 11(4): 284-292. DOI: 10.1016/S1473-3099(11)70024-X.
    [47] Marty FM, Boeckh M. Maribavir and human cytomegalovirus-what happened in the clinical trials and why might the drug have failed?[J]. Curr Opin Virol, 2011, 1(6): 555-562. DOI: 10.1016/j.coviro.2011.10.011.
    [48] Verkaik NJ, Hoek RA, van Bergeijk H, et al. Leflunomide as part of the treatment for multidrug-resistant cytomegalovirus disease after lung transplantation: case report and review of the literature[J]. Transpl Infect Dis, 2013, 15(6): E243-E249. DOI: 10.1111/tid.12156.
    [49] Morita S, Shinoda S, Tamaki S, et al. Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: a case report and literature review[J]. J Clin Virol, 2016, 82(S1): 133-138. DOI: 10.1016/j.jcv.2016.07.015.
    [50] Avery RK, Mossad SB, Poggio E, et al. Utility of leflunomide in the treatment of complex cytomegalovirus syndromes[J]. Transplantation, 2010, 90(4): 419-426. DOI: 10.1097/TP.0b013e3181e94106.
    [51] Sellar RS, Ward KN, Thomson KJ, et al. Evidence for clinical activity of artesunate in multidrug-resistant herpes simplex infection following HSCT[J]. Bone Marrow Transplant, 2012, 47(11): 1482-1483. DOI: 10.1038/bmt.2012.46.
    [52] Ho WE, Peh HY, Chan TK, et al. Artemisinins: pharmacological actions beyond anti-malarial[J]. Pharmacol Ther, 2014, 142(1): 126-139. DOI: 10.1016/j.pharmthera.2013.12.001.
    [53] Uhlin M, Gertow J, Uzunel M, et al. Rapid salvage treatment with virus-specific T cells for therapy-resistant disease[J]. Clin Infect Dis, 2012, 55(8): 1064-1073. doi: 10.1093/cid/cis625
    [54] Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation[J]. Blood, 2013, 121(26): 5113-5123. DOI: 10.1182/blood-2013-02-486324.
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  • 收稿日期:  2016-10-28
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2017-01-15

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