metricas
covid
Buscar en
Enfermedades Infecciosas y Microbiología Clínica
Toda la web
Inicio Enfermedades Infecciosas y Microbiología Clínica Papel de la anidulafungina en el paciente con trasplante de órgano sólido
Información de la revista
Vol. 26. Núm. S14.
Anidulafungina en el tratamiento de la infección fúngica invasora
Páginas 29-34 (diciembre 2008)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 26. Núm. S14.
Anidulafungina en el tratamiento de la infección fúngica invasora
Páginas 29-34 (diciembre 2008)
Acceso a texto completo
Papel de la anidulafungina en el paciente con trasplante de órgano sólido
Role of anidulafungin in solid organ transplant recipients
Visitas
2509
José M. Aguadoa,
Autor para correspondencia
jaguadog@medynet.com

Correspondencia: Unidad de Enfermedades Infecciosas. Hospital Universitario 12 de Octubre. Edificio Materno-Infantil. Planta 6.ª. Avda. Andalucía, km 5,400. 28041 Madrid. España.
, Josefina Ayatsb
a Unidad de Enfermedades Infecciosas. Hospital Universitario 12 de Octubre. Madrid. España
b Servicio de Microbiología. Hospital Universitario de Bellvitge. L’Hospitalet de Llobregat. Barcelona. España
Este artículo ha recibido
Información del artículo

La incidencia de infección fúngica invasora (IFI) en pacientes con trasplante de órgano sólido (TOS) es variable según el tipo de trasplante. Una gran mayoría de estas infecciones son debidas a Candida spp. y menos frecuentemente a Aspergillus spp o a otros hongos, como Cryptococcus spp. En la actualidad, la mortalidad general por IFI en pacientes con TOS oscila entre el 25 y el 80% y la mitad de estas muertes están directamente relacionadas con la infección fúngica. Hay factores de riesgo bien caracterizados que favorecen el desarrollo de IFI en estos pacientes y que nos permiten dirigir la profilaxis antifúngica a los pacientes de mayor riesgo.

Las candinas son una nueva familia de fármacos antifúngicos potencialmente útiles tanto en el tratamiento como en la profilaxis de la IFI en el paciente con TOS. La anidulafungina tiene mejor espectro de acción y menor toxicidad que la caspofungina. Anidulafungina tiene buena actividad antifúngica in vitro contra Candida y Aspergillus spp. Uno de los aspectos más interesantes de anidulafungina, con respecto al paciente con TOS, es que no es metabolizada ni eliminada por el riñón, de forma que no exige ajustes de la dosis en estos pacientes en quienes son frecuentes las alteraciones de la función renal. Por otro lado, tampoco se metaboliza en el hígado, por lo que no hay interferencias con otros fármacos metabolizados en ese órgano ni se requiere modificaciones de la dosis en hepatopatías graves ni con el uso de inmunosupresores, como prednisona, ciclosporina A, tacrolimus, micofenolato mofetilo o sirolimus. Aunque la experiencia es todavía muy limitada, estos datos apuntan a que la anidulafungina será de gran ayuda en el manejo clínico de pacientes con TOS.

Palabras clave:
Anidulafungina
Trasplante de órgano sólido
Infección fúngica
Aspergillus
Candida

The incidence of invasive fungal infections in solid organ transplant recipients varies according to the type of transplant. Most of these infections are due to Candida spp. and less frequently to Aspergillus spp. or other fungi such as Cryptococcus spp. Currently, overall mortality due to invasive fungal infections in solid organ transplant recipients ranges between 25% and 80% and half of these deaths are directly related to the fungal infection. A number of well-defined risk factors favor the development of invasive fungal infections in these patients and allow antifungal prophylaxis in high-risk patients.

The candins are a new class of antifungal agent with potential use both in the treatment and in the prophylaxis of invasive fungal infections in solid organ transplant recipients. Anidulafungin has a wider spectrum of action and lower toxicity than caspofungin. Anidulafungin has good in vitro antifungal activity against Candida and Aspergillus spp. One of the most interesting features of anidulafungin in solid organ transplant recipients is that this drug is not metabolized by or eliminated through the kidney so that dosage adjustments are not required in these patients, who frequently show renal function alterations.

Moreover, anidulafungin is not metabolized in the liver and is consequently free of interactions with other drugs metabolized in this organ. Equally, dosage adjustments are not required in patients with severe liver disease or in those administered immunosuppressive agents such as prednisone, cyclosporin A, tacrolimus, mofetil mycophenolate or sirolimus. Although experience is still limited, these data suggest that anidulafungin will be highly useful in the clinical management of solid organ transplant recipients.

Key words:
Anidulafungin
Solid organ transplantation
Fungal infection
Aspergillus
Candida
El Texto completo está disponible en PDF
Bibliografía
[1.]
J. Briegel, H. Forst, B. Spill, A. Haas, B. Grabein, M. Haller, et al.
Risk factors for systemic fungal infections in liver transplant recipients.
Eur J Clin Microbiol Infect Dis, 14 (1995), pp. 375-382
[2.]
N. Singh, T. Gayowski, M.M. Wagener, H. Doyle, I.R. Marino.
Invasive fungal infections in liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent.
Clin Infect Dis, 24 (1997), pp. 179-184
[3.]
J. Gavalda, O. Len, R. San Juan, J.M. Aguado, J. Fortún, C. Lumbreras, et al.
Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case-control study.
Clin Infect Dis, 41 (2005), pp. 52-59
[4.]
D.L. Paterson, N. Singh.
Invasive aspergillosis in transplant recipients.
Medicine, 78 (1999), pp. 123-138
[5.]
S. Kusne, J. Torre Cisneros, R. Mañez, W. Irish, M. Martin, J. Fung, et al.
Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation.
J Infect Dis, 166 (1992), pp. 1379-1383
[6.]
N. Singh, P.M. Arnow, A. Bonham, E. Dominguez, D.L. Paterson, G.A. Pankey, et al.
Invasive aspergillosis in liver transplant recipients in the 1990.
Transplantation, 64 (1997), pp. 716-720
[7.]
S. Kusne, D. Tobin, A.W. Pasculle, D.H. Van Thiel, M. Ho, T.E. Starzl.
Candida carriage in the alimentary tract of liver transplant candidates.
Transplantation, 57 (1994), pp. 398-402
[8.]
C.V. Paya.
Fungal infections in solid-organ transplantation.
Clin Infect Dis, 16 (1993), pp. 677-688
[9.]
N. Singh.
Antifungal prophylaxis for solid organ transplant recipients: seeking clarity amidst controversy.
Clin Infect Dis, 31 (2000), pp. 545-553
[10.]
J. Fortún, P. Martín-Dávila, S. Moreno, E. De Vicente, J. Nuño, J. Candelas, et al.
Risk factors for invasive Aspergillosis in liver transplant recipients.
Liver Transplant, 8 (2002), pp. 1065-1070
[11.]
J. Canales, C.D. Gove, A.E. Gimson, S.P. Wilkinson, E.N. Wardle, R. Williams.
Reticuloendothelial system and hepatocyte function in fulminant hepatic failure.
Gut, 23 (1982), pp. 265
[12.]
M. Imawari, R.D. Hughes, C.D. Gove, R. Williams.
Fibronectin and Kupffer cell function in fulminant hepatic failure.
Dig Dis Sci, 30 (1985), pp. 1028
[13.]
R. Patel, D. Portela, A.D. Badley, W.S. Harmsen, J.H. Larson-Keller, D.M. Ilstrup, et al.
Risk factors of invasive candida and non-candida fungal infections after liver transplantation.
Transplantation, 62 (1996), pp. 926-934
[14.]
L.A. Collins, M.H. Samore, M.S. Roberts, R. Luzzati, R.L. Jenkins, W.D. Lewis, et al.
Risk factors for invasive fungal infections complicating orthotopic liver transplantation.
J Infect Dis, 170 (1994), pp. 644-652
[15.]
F.P. Silveira, S. Husain.
Fungal Infections in solid organ transplantation.
Med Mycol, 45 (2007), pp. 305-320
[16.]
S. Husain, B.D. Alexander, P. Munoz, R.K. Avery, S. Houston, T. Pruett, et al.
Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi.
Clin Infect Dis, 37 (2003), pp. 221-229
[17.]
M. Nucci.
Emerging moulds: Fusarium, Scedosporium and zygomycetes in transplant recipients.
Curr Opin infec Dis, 16 (2003), pp. 607-612
[18.]
W.J. Steinbach, W.A. Schell, J.R. Blankenship, C. Onyewu, J. Heitman, J.R. Perfect.
In vitro interactions between antifungals and immunosuppressants against Aspergillus fumigatus.
Antimicrob Agents Chemother, 48 (2004), pp. 1664-1669
[19.]
F.M. Marty, C.M. Lowry, C.S. Cutler, B.J. Campbell, K. Fiumara, L.R. Baden, et al.
Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant, 12 (2006), pp. 552-559
[20.]
N. Singh, A.P. Limaye, G. Forrest, N. Safdar, P. Muñoz, K. Pursall, et al.
Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.
Transplantation, 81 (2006), pp. 320-326
[21.]
J.A. Martínez Martínez, J. Mensa Pueyo, F. Marco.
Características generales y farmacocinética de caspogungina.
Drugs Today, 38 (2002), pp. 15-24
[22.]
C. Wagner, W. Graninger, E. Presterl, C. Joukhadar.
The echinocandins: Comparison of their pharmacokinetics, pharmacodynamics and clinical applications.
Pharmacology, 78 (2006), pp. 161-177
[23.]
J.A. Dowell, M. Stogniew, D. Krause, T. Henkel, B. Damle.
Lack of pharmacokinetic interaction between anidulafungin and tacrolimus.
J Clin Pharmacol, 47 (2007), pp. 305-314
[24.]
J.A. Dowell, W. Knebel, T. Ludden, M. Stogniew, D. Krause, T. Henkel.
Population pharmacokinetic analysis of anidulafungin, an echinocandin antifungal.
J Clin Pharmacol, 44 (2004), pp. 590-598
[25.]
J.A. Dowell, M. Stogniew, D. Krause, T. Henkel, I.E. Weston.
Assessment of the safety and pharmacokinetics of anidulafungin when administered with cyclosporine.
J Clin Pharmacol, 45 (2005), pp. 227-233
[26.]
A. Philip, Z. Odabasi, J. Rodriguez, V.L. Paetznick, E. Chen, J.H. Rex, et al.
In vitro synergy testing of anidulafungin with itraconazole, voriconazole, and amphotericin B against Aspergillus spp. and Fusarium spp.
Antimicrob Agents Chemother, 49 (2005), pp. 3572-3574
[27.]
J.A. Dowell, J. Schranz, A. Baruch, G. Foster.
Safety and pharmacokinetics of coadministered voriconazole and anidulafungin.
J Clin Pharmacol, 45 (2005), pp. 1373-1382
[28.]
A.C. Reboli, C. Rotstein, P.G. Pappas, S.W. Chapman, D.M. Kett, D. Kumar, et al.
Anidulafungin versus fluconazole for invasive candidiasis.
N Engl J Med, 356 (2007), pp. 2472-2482
[29.]
B.D. Brielmaier, E. Casabar, C.M. Kurtzeborn, P.S. McKinnon, D.J. Ritchie.
Early clinical experience with anidulafungin at a large tertiary care medical center.
Pharmacotherapy, 28 (2008), pp. 64-73
[30.]
D.J. Winston, A. Pakrasi, R.W. Busuttil.
Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial.
Ann Intern Med, 131 (1999), pp. 729-737
[31.]
V. Monforte, A. Roman, J. Gavalda, C. Bravo, L. Tenorio, A. Ferrer, et al.
Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors.
J Heart Lung Transplant, 20 (2001), pp. 1274-1281
[32.]
J. Gavaldà, T. Martín, P. López, et al.
Efficacy of high loading doses of liposomal amphotericin B in the treatment of experimental invasive pulmonary aspergillosis.
Clin Microbiol Infect, 11 (2005), pp. 999-1004
[33.]
W.D. Colby, M.D. Sharpe, C.N. Ghent, D.R. Grant, L. Hunte, J. McDougall, et al.
Efficacy of itraconazole prophylaxis against systemic fungal infection in liver transplant recipients.
39th Interscience Conference on Antimicrobial Agents and Chemotherapy,
[34.]
N. Singh, L. Mieles, V.L. Yu, T. Gayowski.
Invasive aspergillosis in liver transplant recipients: association with candidemia and consumption coagulopathy and failure of prophylaxis with low-dose amphotericin B.
Clin Infect Dis, 17 (1993), pp. 906-908
[35.]
J. Tollemar, K. Hockerstedt, B.G. Ericzon, H. Jalanko, O. Ringden.
Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study.
Transplantation, 59 (1995), pp. 45-50
[36.]
N. Singh, D.L. Paterson, T. Gayowski, M.M. Wagener.
Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requering renal replacement therapy.
Transplantation, 71 (2001), pp. 910-913
[37.]
J. Fortún, P. Martin-Davila, M. Uriarte, A. Candela, R. Bárcena, E. De Vicente, et al.
Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients.
42nd ICAAC Abstracts. American Society for Microbiology, pp. 315
[38.]
T. Lorf, F. Braun, R. Ruchel, A. Muller, B. Sattler, B. Ringe.
Systemic mycoses during prophylactical use of liposomal amphotericin B (Ambisome) after liver transplantation.
Mycoses, 42 (1999), pp. 47-53
[39.]
E. Varo, S. Tome, M. Bustamante, et al.
Fungal infection prophylaxis in high-risk liver transplant recipients.
38th ICAAC Abstracts, American Society for Microbiology,
[40.]
R. Petraitiene, V. Petraitis, A.H. Groll, T. Sein, R.L. Schaufele, A. Francesconi, et al.
Antifungal efficacy of caspofungin (MK-0991) in experimental pulmonary aspergillosis in persistently neutropenic rabbits: pharmacokinetics, drug disposition, and relationship to galactomannan antigenemia.
Antimicrob Agents Chemother, 46 (2002), pp. 12-23
[41.]
J. Fortún, P. Muñoz, P. Martín-Dávila, et al.
GESITRA Prospective, Multicenter Study of Caspofungin for Prophylaxis in High Risk Liver Transplantation.
46th Interscience Conference on Antimicrobial Agents and Chemotherapy,
Copyright © 2008. Elsevier España S.L.. Todos los derechos reservados
Opciones de artículo
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos