Información del artículo
Resumen
Los receptores de un trasplante de pulmón tienen un riesgo incrementado de infección o enfermedad por citomegalovirus (CMV). Al prevenir este acontecimiento podemos evitar los efectos indirectos relacionados, como son las infecciones fúngicas invasivas y la bronquiolitis obliterante, siendo esta última uno de los factores limitantes de la supervivencia de los pacientes. Las estrategias de prevención han conllevado una importante disminución en la incidencia de la enfermedad por CMV y de su mortalidad relacionada. Las dos principales estrategias para la prevención de la enfermedad por CMV son la profilaxis universal y la terapia anticipada. En el trasplante pulmonar, la eficacia y seguridad del tratamiento anticipado no ha sido bien estudiada, por lo que no se recomienda su uso. La profilaxis universal constituye la mejor estrategia para la prevención de la enfermedad por CMV en los receptores de trasplante de pulmón. No hay un consenso en la comunidad científica acerca de la duración de la profilaxis, pero las guías 2011 de GESITRASEIMC/ REIPI 2011 sobre prevención y tratamiento de la infección por CMV en pacientes trasplantados de órgano sólido recomiendan prolongar 6 meses postrasplante con valganciclovir, excepto en los casos de D+/R–, que es hasta el año si existen dificultades de monitorización. El futuro de la prevención de la enfermedad por CMV debería pasar por las estrategias “inmunoguiadas”.
Palabras clave:
Citomegalovirus
Trasplante de pulmón
Profilaxis
Abstract
Lung transplant recipients, more than other organ transplant recipients, are at particular risk for cytomegalovirus (CMV) infection and disease. CMV prevention avoids the indirect effects of this virus, such as opportunistic fungal infections and obliterative bronchiolitis, the latter being the major limiting factor in the long-term success of lung-transplantation. CMV prevention strategies have significantly reduced CMV disease and CMV-related mortality. Two major strategies are commonly used for CMV prevention: universal prophylaxis and preemptive therapy. In lung transplant recipients, the efficacy and safety of preemptive treatment have not been studied and therefore, cannot be recommended. Universal prophylaxis is the best strategy for preventing CMV disease in lung transplant recipients. There is no consensus on the optimal duration of prophylaxis, but the recently published GESITRA-SEIMC/REIPI 2011 Guidelines for the management of CMV infection in solid-organ transplant patients recommend 6 months posttransplantation. In D+/R− recipients, this period can be prolonged to 12 months if there are difficulties in monitoring at 6 months posttransplantation. The future of prevention will probably depend on immunoguided strategies.
Keywords:
Cytomegalovirus
Lung transplantation
Prophylaxis
El Texto completo está disponible en PDF
Bibliografía
[1.]
S.R. Duncan, W.F. Grgurich, A.T. Iacono, G.J. Burckart, S.A. Yousem, I.L. Paradis, et al.
A comparison of ganciclovir and acyclovir to prevent cytomegalovirus after lung transplantation.
Am J Respir Crit Care Med, 150 (1994), pp. 146-152
[2.]
N.A. Ettinger, T.C. Bailey, E.P. Trulock, G.A. Storch, D. Anderson, S. Raab, et al.
Cytomegalovirus infection and pneumonitis. Impact after isolated lung transplantation. Washington University Lung Transplant Group.
Am Rev Respir Dis, 147 (1993), pp. 1017-1023
[3.]
J. Gavaldá, A. Román.
Infection in lung transplantation.
Enferm Infecc Microbiol Clin, 25 (2007), pp. 639-649
[4.]
M. Aguilar-Guisado, J. Givaldá, P. Ussetti, A. Ramos, P. Morales, M. Blanes, et al.
Pneumonia after lung transplantation in the RESITRA Cohort: a multicenter prospective study.
Am J Transplant, 7 (2007), pp. 1989-1996
[5.]
P. Jaksch, B. Zweytick, H. Kerschner, A.M. Hoda, M. Keplinger, G. Lang, et al.
Cytomegalovirus prevention in high-risk lung transplant recipients: comparison of 3- vs 12-month valganciclovir therapy.
J Heart Lung Transplant, 28 (2009), pp. 670-675
[6.]
V. Monforte, C. López, F. Santos, F. Zurbano, M. De la Torre, A. Sole, et al.
A multicenter study of valganciclovir prophylaxis up to day 120 in CMV-seropositive lung transplant recipients.
Am J Transplant, 9 (2009), pp. 1134-1141
[7.]
S.M. Palmer, A.P. Limaye, M. Banks, D. Gallup, J. Chapman, E.C. Lawrence, et al.
Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.
Ann Intern Med, 152 (2010), pp. 761-769
[8.]
M.R. Zamora, M.R. Nicolls, T.N. Hodges, J. Marquesen, T. Astor, T. Grazia, et al.
Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation.
Am J Transplant, 4 (2004), pp. 1635-1642
[9.]
M.R. Zamora.
DNA viruses (CMV, EBV, and the Herpesviruses).
Semin Respir Crit Care Med, 32 (2011), pp. 454-470
[10.]
V. Bohm, C.K. Seckert, C.O. Simon, D. Thomas, A. Renzaho, D. Gendig, et al.
Immune evasion proteins enhance cytomegalovirus latency in the lungs.
J Virol, 83 (2009), pp. 10293-10298
[11.]
O.A. Shlobin, E.E. West, N. Lechtzin, S.M. Miller, M. Borja, J.B. Orens, et al.
Persistent cytomegalovirus-specific memory responses in the lung allograft and blood following primary infection in lung transplant recipients.
J Immunol, 176 (2006), pp. 2625-2634
[12.]
A.J. Koffron, M. Hummel, B.K. Patterson, S. Yan, D.B. Kaufman, J.P. Fryer, et al.
Cellular localization of latent murine cytomegalovirus.
J Virol, 72 (1998), pp. 95-103
[13.]
M. Balthesen, L. Dreher, P. Lucin, M.J. Reddehase.
The establishment of cytomegalovirus latency in organs is not linked to local virus production during primary infection.
J Gen Virol, 75 (1994), pp. 2329-2336
[14.]
M. Balthesen, M. Messerle, M.J. Reddehase.
Lungs are a major organ site of cytomegalovirus latency and recurrence.
J Virol, 67 (1993), pp. 5360-5366
[15.]
J. Gavaldá, A. Román, A. Pahissa.
Risks and epidemiology of infections after lung or heart-lung transplantation.
Transplant Infections, 3rd, pp. 114-137
[16.]
D. Mitsani, M.H. Nguyen, D.M. Girnita, K. Spichty, E.J. Kwak, F.P. Silveira, et al.
A polymorphism linked to elevated levels of interferon-gamma is associated with an increased risk of cytomegalovirus disease among Caucasian lung transplant recipients at a single center.
J Heart Lung Transplant, 30 (2011), pp. 523-529
[17.]
P. Ljungman, P. Griffiths, C. Paya.
Definitions of cytomegalovirus infection and disease in transplant recipients.
Clin Infect Dis, 34 (2002), pp. 1094-1097
[18.]
J. Torre-Cisneros, M.C. Fariñas, J.J. Castón, J.M. Aguado, S. Cantisán, J. Carratalá, et al.
GESITRA-SEIMC/REIPI recommendations for the management of cytomegalovirus infection in solid-organ transplant patients.
Enferm Infecc Microbiol Clin, 29 (2011), pp. 735-758
[19.]
R.N. Husni, S.M. Gordon, D.L. Longworth, A. Arroliga, P.C. Stillwell, R.K. Avery, et al.
Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients.
Clin Infect Dis, 26 (1998), pp. 753-755
[20.]
D.R. Snydman, A.P. Limaye, L. Potena, M.R. Zamora.
Update and review: state-of-theart management of cytomegalovirus infection and disease following thoracic organ transplantation.
Transplant Proc, 433 (2011), pp. S1-S17
[21.]
O. Manuel, D. Kumar, G. Moussa, M.H. Chen, J. Pilewski, K.R. McCurry, et al.
Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis.
Transplantation, 87 (2009), pp. 719-725
[22.]
C. Chmiel, R. Speich, M. Hofer, D. Michel, T. Mertens, W. Weder, et al.
Ganciclovir/valganciclovir prophylaxis decreases cytomegalovirus-related events and bronchiolitis obliterans syndrome after lung transplantation.
Clin Infect Dis, 46 (2008), pp. 831-839
[23.]
E. Ruttmann, C. Geltner, B. Bucher, H. Ulmer, D. Hofer, H.B. Hangler, et al.
Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation.
Transplantation, 81 (2006), pp. 1415-1420
[24.]
H. Bonatti, W. Tabarelli, E. Ruttmann, R. Kafka, C. Larcher, D. Hofer, et al.
Impact of cytomegalovirus match on survival after cardiac and lung transplantation.
Am Surg, 70 (2004), pp. 710-714
[25.]
V.G. Valentine, D. Weill, M.R. Gupta, B. Raper, S.G. Laplace, G.A. Lombard, et al.
Ganciclovir for cytomegalovirus: a call for indefinite prophylaxis in lung transplantation.
J Heart Lung Transplant, 27 (2008), pp. 875-881
[26.]
L.D. Sharples, K. McNeil, S. Stewart, J. Wallwork.
Risk factors for bronchiolitis obliterans: a systematic review of recent publications.
J Heart Lung Transplant, 21 (2002), pp. 271-281
[27.]
D.M. Zuk, A. Humar, J.G. Weinkauf, D.C. Lien, R.G. Nador, D. Kumar.
An international survey of cytomegalovirus management practices in lung transplantation.
Transplantation, 90 (2010), pp. 672-676
[28.]
D. Emanuel, I. Cunningham, K. Jules-Elysee, J.A. Brochstein, N.A. Kernan, J. Laver, et al.
Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin.
Ann Intern Med, 109 (1988), pp. 777-782
[29.]
D.R. Sokos, M. Berger, H.M. Lazarus.
Intravenous immunoglobulin: appropriate indications and uses in hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant, 8 (2002), pp. 117-130
[30.]
B.T. Alexander, L.M. Hladnik, K.M. Augustin, E. Casabar, P.S. McKinnon, R.M. Reichley, et al.
Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.
Pharmacotherapy, 30 (2010), pp. 554-561
[31.]
B.T. Alexander, L.M. Hladnik, K.M. Augustin, E. Casabar, P.S. McKinnon, R.M. Reichley, et al.
Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.
Pharmacotherapy, 30 (2010), pp. 554-561
[32.]
P. Ljungman, D. Engelhard, H. Link, P. Biron, L. Brandt, S. Brunet, et al.
Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group.
Clin Infect Dis, 14 (1992), pp. 831-835
[33.]
C.M. Isada, B. Yen-Lieberman, N.S. Lurain, R. Schilz, D. Kohn, D.L. Longworth, et al.
Clinical characteristics of 13 solid organ transplant recipients with ganciclovirresistant cytomegalovirus infection.
Transpl Infect Dis, 4 (2002), pp. 189-194
[34.]
M.R. Zamora, R.D. Davis, C. Leonard.
Management of cytomegalovirus infection in lung transplant recipients: evidence-based recommendations.
Transplantation, 80 (2005), pp. 157-163
[35.]
S. Chou, C.L. Meichsner.
A nine-codon deletion mutation in the cytomegalovirus UL97 phosphotransferase gene confers resistance to ganciclovir.
Antimicrob Agents Chemother, 44 (2000), pp. 183-185
[36.]
S. Chou, R.H. Waldemer, A.E. Senters, K.S. Michels, G.W. Kemble, R.C. Miner, et al.
Cytomegalovirus UL97 phosphotransferase mutations that affect susceptibility to ganciclovir.
J Infect Dis, 185 (2002), pp. 162-169
[37.]
I.L. Smith, J.M. Cherrington, R.E. Jiles, M.D. Fuller, W.R. Freeman, S.A. Spector.
High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes.
J Infect Dis, 176 (1997), pp. 69-77
[38.]
A. Weinberg, D.A. Jabs, S. Chou, B.K. Martin, N.S. Lurain, M.S. Forman, et al.
Mutations conferring foscarnet resistance in a cohort of patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.
J Infect Dis, 187 (2003), pp. 777-784
[39.]
J.C. Méndez, I.G. Sia, K.R. Tau, M.J. Espy, T.F. Smith, S. Chou, et al.
Novel mutation in the CMV UL97 gene associated with resistance to ganciclovir therapy.
Transplantation, 67 (1999), pp. 755-757
[40.]
N.S. Lurain, A. Weinberg, C.S. Crumpacker, S. Chou.
Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing.
Antimicrob Agents Chemother, 45 (2001), pp. 2775-2780
[41.]
S. Chou, N.S. Lurain, K.D. Thompson, R.C. Miner, W.L. Drew.
Viral DNA polymerase mutations associated with drug resistance in human cytomegalovirus.
J Infect Dis, 188 (2003), pp. 32-39
[42.]
I.L. Smith, J.M. Cherrington, R.E. Jiles, M.D. Fuller, W.R. Freeman, S.A. Spector.
High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes.
J Infect Dis, 176 (1997), pp. 69-77
[43.]
D. Mitsani, M.H. Nguyen, E.J. Kwak, F.P. Silveira, A. Vadnerkar, J. Pilewski, et al.
Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis.
J Heart Lung Transplant, 29 (2010), pp. 1014-1020
[44.]
A.J. Reddy, A.K. Zaas, K.E. Hanson, S.M. Palmer.
A single-center experience with ganciclovir-resistant cytomegalovirus in lung transplant recipients: treatment and outcome.
J Heart Lung Transplant, 26 (2007), pp. 1286-1292
[45.]
G. Boivin, N. Goyette, C. Gilbert, A. Humar, E. Covington.
Clinical impact of ganciclovirresistant cytomegalovirus infections in solid organ transplant patients.
Transpl Infect Dis, 7 (2005), pp. 166-170
[46.]
A.P. Limaye.
Antiviral resistance in cytomegalovirus: an emerging problem in organ transplant recipients.
Semin Respir Infect, 17 (2002), pp. 265-273
[47.]
S.M. Bhorade, N.S. Lurain, A. Jordan, J. Leischner, J. Villanueva, R. Durazo, et al.
Emergence of ganciclovir-resistant cytomegalovirus in lung transplant recipients.
J Heart Lung Transplant, 21 (2002), pp. 1274-1282
[48.]
A.P. Limaye, G. Raghu, D.M. Koelle, J. Ferrenberg, M.L. Huang, M. Boeckh.
High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy.
J Infect Dis, 185 (2002), pp. 20-27
[49.]
R.M. Kruger, W.D. Shannon, M.Q. Arens, J.P. Lynch, G.A. Storch, E.P. Trulock.
The impact of ganciclovir-resistant cytomegalovirus infection after lung transplantation.
Transplantation, 68 (1999), pp. 1272-1279
[50.]
D.R. Kaul, S. Stoelben, E. Cober, T. Ojo, E. Sandusky, P. Lischka, et al.
First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246.
Am J Transplant, 11 (2011), pp. 1079-1084
[51.]
T. Goldner, G. Hewlett, N. Ettischer, H. Ruebsamen-Schaeff, H. Zimmermann, P. Lischka.
The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase.
J Virol, 85 (2011), pp. 10884-10893
[52.]
P. Lischka, G. Hewlett, T. Wunberg, J. Baumeister, D. Paulsen, T. Goldner, et al.
In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246.
Antimicrob Agents Chemother, 54 (2010), pp. 1290-1297
[53.]
M.W. Gerbase, D. Dubois, C. Rothmeier, A. Spiliopoulos, W. Wunderli, L.P. Nicod.
Costs and outcomes of prolonged cytomegalovirus prophylaxis to cover the enhanced immunosuppression phase following lung transplantation.
Chest, 116 (1999), pp. 1265-1272
[54.]
J.L. Kelly, R.K. Albert, D.E. Wood, G. Raghu.
Efficacy of a 6-week prophylactic ganciclovir regimen and the role of serial cytomegalovirus antibody testing in lung transplant recipients.
Transplantation, 59 (1995), pp. 1144-1147
[55.]
M.R. Zamora.
Cytomegalovirus and lung transplantation.
Am J Transplant, 4 (2004), pp. 1219-1226
[56.]
S. Lefeuvre, P. Chevalier, C. Charpentier, R. Zekkour, L. Havard, M. Benammar, et al.
Valganciclovir prophylaxis for cytomegalovirus infection in thoracic transplant patients: retrospective study of efficacy, safety, and drug exposure.
Transpl Infect Dis, 12 (2010), pp. 213-219
[57.]
L.R. Minces, M.H. Nguyen, E.J. Kwak, F.P. Silveira, R.C. Abdel Massih, R.K. Shields, et al.
Indefinite valganciclovir prophylaxis (VGC px) among D+/R- lung transplant (LTx) recipients reduces CMV disease but is limited by toxicity. V-497.
51th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),
[58.]
R.M. Kruger, S. Paranjothi, G.A. Storch, J.P. Lynch, E.P. Trulock.
Impact of prophylaxis with cytogam alone on the incidence of CMV viremia in CMV-seropositive lung transplant recipients.
J Heart Lung Transplant, 22 (2003), pp. 754-763
[59.]
J.R. Maurer, G. Snell, A. DeHoyos, S. Kesten, T. Winton.
Outcomes of lung transplantation using three different cytomegalovirus prophylactic regimens.
Transplant Proc, 25 (1993), pp. 1434-1435
[60.]
F.K. Gould, R. Freeman, C.E. Taylor, T. Ashcroft, J.H. Dark, P.A. Corris.
Prophylaxis and management of cytomegalovirus pneumonitis after lung transplantation: a review of experience in one center.
J Heart Lung Transplant, 12 (1993), pp. 695-699
[61.]
H.A. Valantine, H. Luikart, R. Doyle, J. Theodore, S. Hunt, P. Oyer, et al.
Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.
Transplantation, 72 (2001), pp. 1647-1652
Copyright © 2011. Elsevier España S.L.. Todos los derechos reservados
