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Inicio Enfermedades Infecciosas y Microbiología Clínica Latest developments in fungal lung infection in solid organ transplantation (SOT...
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Vol. 26. Issue S3.
Pages 49-57 (April 2008)
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Vol. 26. Issue S3.
Pages 49-57 (April 2008)
Monographic: “update on infectious diseases”
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Latest developments in fungal lung infection in solid organ transplantation (SOT)
Últimos avances en las infecciones micóticas pulmonares ocurridas en el trasplante de órganos sólidos (TOS)
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Amparo Soléa,
Corresponding author
sole_amp@gva.es

Correspondence: Dra. A. Solé. Unidad de trasplante pulmonar. Hospital Universitario La Fe. Avda. Campanar, 21. 46009 Valencia. Spain.
, Jordi Carrataláb, Miguel Montejoc, Patricia Muñozd, Guillermo Quindóse, Mercedes Palomarf, Javier Pemáng, Juan Carlos Pozoh, Juan Luis Rodríguez Tudelai
a Hospital Universitario La Fe. Valencia. Spain
b Hospital Universitario de Bellvitge. Barcelona. Spain
c Hospital de Cruces. Universidad del País Vasco. Bilbao. Spain
d Hospital General Universitario Gregorio Marañón. Madrid. Spain
e Facultad de Medicina y Odontología. Universidad del País Vasco. Bilbao. Spain
f Hospital Vall d’Hebron. Barcelona. Spain
g Hospital Universitario La Fe. Valencia. Spain
h Hospital Reina Sofía. Córdoba. Spain
i Centro Nacional de Microbiología. Instituto de Salud Carlos III. Madrid. Spain
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The incidence of invasive mycoses following solid organ transplant (SOT) ranges from 5 to 42% depending on the organ transplanted. Despite the increasing impact of viral infections in SOT, fungal infections still have a main role in transplant recipients. In fact, they remain a common cause of morbidity and mortality in the early and late post-transplant periods. Aspergillus spp. and Candida spp. account for most IFI, but recent epidemiological and clinical studies suggest the emergence of mycelia fungi other than Aspergillus as well as resistant strains of Candida in these patients. Due to the difficulty in making a definitive diagnosis, the treatment is sometimes delayed or is not prescribed (post-mortem diagnosis). Serological and molecular detection of Aspergillus antigens or fungal DNA, in blood and/or BAL samples, may improve the diagnosis of pulmonary aspergillosis, but in SOT the sensitivity is variable and more studies are needed.

Another pendent issue is antifungal prophylaxis in SOT recipients; it is unknown which is the best agent or the time duration, and in which receptors must be applied.

Treatment combining AmB preparations, newer antifungal drugs, early surgical resection of infected tissue and discontinuation or modulation of immunosuppressive treatment can to be necessary in selected patients and in certain occasions, and all of them may improve prognosis of IFI. However, there are two main handicaps in the management of FI in transplant recipients: firstly, to establish an early diagnosis, secondly, delays in applying early treatment with antifungal drugs.

Development of new early diagnostic tools more precise and well-designed multicenter evaluations of diagnostic methods and therapeutic regimens available at present are the important work in the next 3-5 years. This review highlights changing spectrum of invasive fungal infections, risk factors, antifungal prophylaxis, and treatment following SOT.

Key words:
Fungal infections
Solid organ tranplantation
Opportunistic infections
Invasive aspergillosis
Prophylaxis

La incidencia de las micosis invasivas después del trasplante de órganos sólidos (TOS) oscila del 5 al 42%, según el órgano trasplantado. A pesar del creciente impacto de las infecciones víricas sobre el TOS, las infecciones micóticas desempeñan todavía un papel principal en los receptores de trasplantes. De hecho, siguen siendo una causa común de morbilidad y mortalidad en las fases precoz y tardía postrasplante.

Aunque Aspergillus spp. y Candida spp. son responsables de la mayoría de infecciones fúngicas invasivas (IFI), recientes estudios epidemiológicos y clínicos sugieren la eclosión de micelios diferentes de Aspergillus, así como de cepas resistentes de Candida, en estos pacientes. Debido a la dificultad de realizar un diagnóstico definitivo, a veces se retrasa el tratamiento o no llega a prescribirse (diagnóstico post-mortem). La detección serológica y molecular de los antígenos de Aspergillus o del ADN fúngico, en muestras de sangre y/o lavado broncoalveolar (LBA), puede mejorar el diagnóstico de la aspergilosis pulmonar, pero en el TOS la sensibilidad es variable y es necesario realizar nuevos estudios al respecto. Otro tema pendiente es la profilaxis antifúngica en los receptores de TOS; se desconoce cuál es el agente más idóneo, así como la duración adecuada de la profilaxis y a qué receptores debe aplicarse. Los tratamientos combinados con preparados de anfotericina B, nuevos fármacos antifúngicos, resección quirúrgica precoz de los tejidos infectados e interrupción o modulación del tratamiento inmunosupresor, pueden ser necesarios en determinados pacientes y en ciertas ocasiones, y todos ellos pueden mejorar el pronóstico de las IFI. Sin embargo, existen dos obstáculos importantes para el tratamiento de las infecciones fúngicas en los receptores de trasplantes: en primer lugar, el establecimiento de un diagnóstico precoz; y en segundo lugar, los retrasos en el tratamiento precoz con fármacos antifúngicos. El desarrollo de nuevos métodos de diagnóstico precoz más precisos, y los estudios multicéntricos bien diseñados sobre los métodos diagnósticos y las pautas terapéuticas disponibles actualmente, son trabajos importantes a realizar durante los próximos 3-5 años. En la presente revisión se subrayan el espectro cambiante de las infecciones fúngicas invasivas, la profilaxis antifúngica y el tratamiento después del TOS.

Palabras clave:
Infecciones fúngicas
Trasplante de órganos sólidos
Infecciones oportunistas
Aspergilosis invasiva
Profilaxis
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References
[1.]
R.M. Kotloff, V.N. Ahya, S.W. Crawford.
Pulmonary complications of solid organ and hematopoietic stem cell transplantation.
Am J Respir Crit Care M, 170 (2004), pp. 22-48
[2.]
N. Singh.
Fungal infections in the recipients of solid organ transplantation.
Infect. Dis. Clin. North Am, 17 (2003), pp. 113-134
[3.]
P.E. Marik.
Fungal infections in solid organ Transplantation.
Expert Opin Pharmacother, 7 (2006), pp. 297-305
[4.]
N. Singh, D.L. Paterson.
Aspergillus infections in transplant recipients.
Clin Microbiol Rev, 18 (2005), pp. 44-69
[5.]
N. Singh, A. Limaye, G. Forrest, N. Safdar, P. Muñoz, K. Pursell, et al.
Lateonset invasive aspergillosis in organ transplant recipients in the current era.
Medical Mycology, 44 (2006), pp. 445-449
[6.]
J. Gavalda, O. Len, R. San Juan, et al.
Risk factors for invasive aspergillosis in solid-organ transplant recipients: a case control study.
Clin Infect Dis, 41 (2005), pp. 52-59
[7.]
R. San Juan Garrido, J.M. Aguado, C. Díaz-Pedroche, O. Len, M. Montejo, A. Moreno, et al.
A review of critical periods for opportunistic infection in the new transplantation era.
Transplantation, 82 (2006), pp. 1457-1462
[8.]
R. San Juan Garrido, J.M. Aguado, C. Lumbreras, C. Díaz-Pedroche, F. López Medrano, M. Lizasoain, et al.
Incidence, clinical characteristics and risk factor late infection in solid organ transplant recipients. Data from RESITRA study group.
Am J Transplant, 7 (2007), pp. 964-971
[9.]
N.G. Almyroudis, D.A. Suttone, P. Linden, M.G. Rinaldie, J. Fung, S. Kusne.
Zygomycosis in solid organ transplant recipients in a tertiary transplant center and review of the literature.
Am J Transplant, 6 (2006), pp. 2365-2374
[10.]
S. Husain, B.D. Alexander, P. Muñoz, 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
[11.]
N. Singh, R.K. Avery, P. Muñoz, et al.
Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients.
Clin Infect Dis, 36 (2003), pp. 46-52
[12.]
N. Singh, M.M. Wagener, I.R. Marino, T. Gayoski.
Trends in invasive fungal infections in liver transplant recipients: correlation with evolution in transplantation practices.
Transplantation, 73 (2002), pp. 63-67
[13.]
A. Solé, P. Morant, M. Salavert, J. Pemán, P. Morales, Valencia Lung Transplant Group.
Aspergillus infections in lung transplant recipients: risk factors and outcome.
Clin Microbiol Infect, 11 (2005), pp. 359-365
[14.]
B. Mehrad, G. Paciocco, F.J. Martínez, et al.
Spectrum of Aspergillus infection in lung transplant recipients: case series and review of the literature.
Chest, 119 (2001), pp. 169-175
[15.]
N. Singh, S. Husain.
Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.
J Heart Lung Transplant, 22 (2003), pp. 258-266
[16.]
P. Muñoz, C. Rodríguez, E. Bouza, et al.
Risk factors of invasive aspergillosis after heart transplantation: protective role of oral itraconazole prophylaxis.
Am J Transplant, 4 (2004), pp. 636-643
[17.]
B.H. Segal, T.J. Walsh.
Current approaches to diagnosis and treatment of invasive aspergillosis.
Am J Respir Crit Care Med, 173 (2006), pp. 707-717
[18.]
R.A. Vilchez, E.J. Kwak, S. Kusne.
Advances in diagnosis and management of invasive fungal infections in organ transplant recipients.
Current Opinion in Organ Transplantation, 7 (2002), pp. 320-324
[19.]
Zaas AK, Alexander BD. Galactomannan and advances in fungal diagnostics. Current Opinion in Organ Transplantation. 200;10:307-11.
[20.]
E.J. Kwak, S. Husain, A. Obman, et al.
Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay for diagnosis of invasive aspergillosis in liver transplant recipients.
J Clin Microbiol, 42 (2004), pp. 435-438
[21.]
C.D. Pfeiffer, J.P. Fine, N. Safdar.
Diagnosis of invasive Aspergillosis using a galactomannan assay: A meta-analysis.
Clin Infect Dis, 42 (2006), pp. 1417-1427
[22.]
S.S. Magill.
Antifungal prophylaxis in transplant recipients: where do we go from here?.
Transpl Infect Dis, 8 (2006), pp. 187-189
[23.]
Playford EG, Webster AC, Sorrell TC, Craig JC. Systematic review and meta-analysis of antifungal agents for preventing fungal infections in liver transplant recipients. Eur J Clin Microbiol Infect 2006 Dis DOI 10.1007/s10096-006-0182-3.
[24.]
R.R. Razonable, C.V. Paya.
Fungal infections in liver transplantation: prophylaxis, surveillance, and treatment.
Current Opinion in Organ Transplantation, 7 (2002), pp. 137-143
[25.]
N. Sing, D.L. Paterson, T. Gayowski, M.M. Wagener, I.R. Marino.
Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy.
Transplantation, 71 (2001), pp. 910-913
[26.]
J. Fortun, P. Martín-Davila, S. Moreno, et al.
Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients.
J Antimicrob Chemother, 52 (2003), pp. 813-819
[27.]
S. Husain, D. Zaldonis, S. Kusne, E.J. Kwak, D.L. Paterson, K.R. McCurry.
Variation in antifungal prophylaxis strategies in lung transplantation.
Transpl Infect Dis, 8 (2006), pp. 213-218
[28.]
M.B. Covarrubias, A.B. Milstone.
An overview of fungal prophylaxis in lung transplantation.
Current Opinion in Organ Transplantation, 10 (2005), pp. 227-232
[29.]
V. Monforte, A. Roman, J. Gavalda, et al.
Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients.
Transplantation, 75 (2003), pp. 1571-1574
[30.]
S.M. Palmer, R.H. Drew, J.D. Whitehouse, et al.
Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.
Transplantation, 72 (2001), pp. 545-548
[31.]
R.H. Drew, A.E. Dodds, D.K. Benjamin Jr, et al.
Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.
Transplantation, 77 (2004), pp. 232-237
[32.]
N. Singh, A.P. Limaye, G. Forrest, 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
[33.]
R. Herbrecht, D.W. Denning, T.F. Patterson, et al.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis.
N Engl J Med, 347 (2002), pp. 408
[34.]
C. Viscoli.
Combination therapy for invasive aspergillosis.
Clin Infect Dis, 39 (2004), pp. 803
[35.]
D.W. Denning.
Echinocandin antifungal drugs.
Lancet, 362 (2003), pp. 1142-1151
[36.]
Cancidas (caspofungin acetate) Summary of product characteristics. Document European Public Assessment Report, The European Agency for the Evaluation of Medicinal Products (2005).
[37.]
B.H. Segal, L.A. Barnhart, V.L. Anderson, T.J. Walsh, et al.
Posaconazole as salvage therapy in patients with chronic granulomatous disease with invasive filamentous fungal infection.
Clin Infect Dis, 40 (2005), pp. 1684-1688
[38.]
T.J. Walsh, I. Raad, T.F. Patterson, et al.
Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An external controlled trial.
Clin Infect Dis, 44 (2007), pp. 2-12
[39.]
B.H. Segal, J.K. Chung, T. Walsh, et al.
Immunotherapy for fungal infections.
Clin Infectious Dis, 42 (2006), pp. 507-515
[40.]
J. Pachl, et al.
A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis.
Clin Infectious Dis, 42 (2006), pp. 507-515
Copyright © 2008. Elsevier España S.L.. All rights reserved
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