Abstract
Invasive aspergillosis (IA) continues to be a significant cause of morbidity and mortality in solid organ transplant recipients. The highest incidence of IA is noted in lung transplant recipients, while the lowest incidence is in kidney transplant recipients. Common risk factors for the development of invasive aspergillosis include environmental exposures and net state of immunosuppression. Unique risk factors to lung transplants include airway colonization, and receipt of single lung transplant. Liver transplant recipients receiving renal replacement therapy on the other hand have the highest risk of IA. Liver transplant recipients also have the highest incidence of disseminated disease while tracheobronchitis is the most common manifestation of IA in lung transplant recipients. Prophylaxis with antifungal agents is recommended in lung and liver transplant recipients. The drug of choice for the treatment of IA remains to be voriconazole. The role of combination therapy for the treatment of IA in solid organ transplant recipients remains undetermined.
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References
Silveira, F. P. & Husain, S. (2007) Fungal infections in solid organ transplantation. Med Mycol, 45, 305–20.
Singh, N. & Paterson, D. L. (2005) Aspergillus infections in transplant recipients. Clin Microbiol Rev, 18, 44–69.
Cahill, B. C., Hibbs, J. R., Savik, K., Juni, B. A., Dosland, B. M., Edin-Stibbe, C. & Hertz, M. I. (1997) Aspergillus airway colonization and invasive disease after lung transplantation. Chest, 112, 1160–64.
Husain, S., Kwak, E. J., Obman, A., Wagener, M. M., Kusne, S., Stout, J. E., Mccurry, K. R. & Singh, N. (2004) Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Am J Transplant, 4, 796–802.
Husni, R. N., Gordon, S. M., Longworth, D. L., Arroliga, A., Stillwell, P. C., Avery, R. K., Maurer, J. R., Mehta, A. & Kirby, T. (1998) Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients. Clin Infect Dis, 26, 753–55.
Mehrad, B., Paciocco, G., Martinez, F. J., Ojo, T. C., Iannettoni, M. D. & Lynch, J. P., 3RD (2001) Spectrum of Aspergillus infection in lung transplant recipients: case series and review of the literature. Chest, 119, 169–75.
Minari, A., Husni, R., Avery, R. K., Longworth, D. L., Decamp, M., Bertin, M., Schilz, R., Smedira, N., Haug, M. T., Mehta, A. & Gordon, S. M. (2002) The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants. Transpl Infect Dis, 4, 195–200.
Westney, G. E., Kesten, S., De Hoyos, A., Chapparro, C., Winton, T. & Maurer, J. R. (1996) Aspergillus infection in single and double lung transplant recipients. Transplantation, 61, 915–19.
Singh, N. & Husain, S. (2003) Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management. J Heart Lung Transplant, 22, 258–66.
Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. A., Leung, A. N., Robbins, R. C. & Stevens, D. A. (2003) Invasive aspergillosis in the setting of cardiac transplantation. Clin Infect Dis, 37 Suppl 3, S281–92.
Munoz, P., Rodriguez, C., Bouza, E., Palomo, J., Yanez, J. F., Dominguez, M. J. & Desco, M. (2004) Risk factors of invasive aspergillosis after heart transplantation: protective role of oral itraconazole prophylaxis. Am J Transplant, 4, 636–43.
Singh, N. (2000) Antifungal prophylaxis for solid organ transplant recipients: seeking clarity amidst controversy. Clin Infect Dis, 31, 545–53.
Cornet, M., Fleury, L., Maslo, C., Bernard, J. F. & Brucker, G. (2002) Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. J Hosp Infect, 51, 288–96.
Morgan, J., Wannemuehler, K. A., Marr, K. A., Hadley, S., Kontoyiannis, D. P., Walsh, T. J., Fridkin, S. K., Pappas, P. G. & Warnock, D. W. (2005) Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med Mycol, 43 Suppl 1, S49–58.
George, M. J., Snydman, D. R., Werner, B. G., Griffith, J., Falagas, M. E., Dougherty, N. N. & Rubin, R. H. (1997) The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med, 103, 106–13.
Snydman, D. R., Falagas, M. E., Avery, R., Perlino, C., Ruthazer, R., Freeman, R., Rohrer, R., Fairchild, R., O’rourke, E., Hibberd, P. & Werner, B. G. (2001) Use of combination cytomegalovirus immune globulin plus ganciclovir for prophylaxis in CMV-seronegative liver transplant recipients of a CMV-seropositive donor organ: a multicenter, open-label study. Transplant Proc, 33, 2571–75.
Snydman, D. R., Werner, B. G., Heinze-Lacey, B., Berardi, V. P., Tilney, N. L., Kirkman, R. L., Milford, E. L., Cho, S. I., Bush, H. L., JR., Levey, A. S. et al. (1987) Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med, 317, 1049–54.
Rubin, R. H. (1989) The indirect effects of cytomegalovirus infection on the outcome of organ transplantation. JAMA, 261, 3607–09.
Chan, K. M. & Allen, S. A. (2002) Infectious pulmonary complications in lung transplant recipients. Semin Respir Infect, 17, 291–302.
Higgins, R., Mcneil, K., Dennis, C., Parry, A., Large, S., Nashef, S. A., Wells, F. C., Flower, C. & Wallwork, J. (1994) Airway stenoses after lung transplantation: management with expanding metal stents. J Heart Lung Transplant, 13, 774–78.
Goldfarb, N. S., Avery, R. K., Goormastic, M., Mehta, A. C., Schilz, R., Smedira, N., Pien, L., Haug, M. T., Gordon, S. M., Hague, L. K., Dresing, J. M., Evans-Walker, T. & Maurer, J. R. (2001) Hypogammaglobulinemia in lung transplant recipients. Transplantation, 71, 242–46.
Crespo, M. M., Raza, K., Johnson, B. A., Mccurry, K. R., Pilewski, J. & Husain, S. (2006) Risk of pulmonary aspergillosis after bronchial stent placement in lung transplant (LTX) recipients. in 26th Annual Meeting and Scientific Sessions of the International Society of Heart and Lung Transplantation.. Madrid, Spain.
Kubak, B. M. (2002) Fungal infection in lung transplantation. Transpl Infect Dis, 4 Suppl 3, 24–31.
Gordon, S. M. & Avery, R. K. (2001) Aspergillosis in lung transplantation: incidence, risk factors, and prophylactic strategies. Transpl Infect Dis, 3, 161–67.
Paradis, I. L. & Williams, P. (1993) Infection after lung transplantation. Semin Respir Infect, 8, 207–15.
Nunley, D. R., Ohori, P., Grgurich, W. F., Iacono, A. T., Williams, P. A., Keenan, R. J. & Dauber, J. H. (1998) Pulmonary aspergillosis in cystic fibrosis lung transplant recipients. Chest, 114, 1321–29.
Husain, S., Raza, K., Paterson, D. L., Pilewski, J., Spichty, K., Zaldonis, D., Carey, M. E., Kowlaski, R., Post, D., Britz, J., Mccurry, K. R. & Zeevi, A. (2007) Impact of various infectious syndromes on the immune function profile in lung transplant recipients. Am J Transplant, 7, 245–6.
Fortun, J., Martin-Davila, P., Moreno, S., De Vicente, E., Nuno, J., Candelas, A., Barcena, R. & Garcia, M. (2002) Risk factors for invasive aspergillosis in Liver Transplant recipients. Liver Transpl, 8, 1065–70.
Singh, N., Pruett, T. L., Houston, S., Munoz, P., Cacciarelli, T. V., Wagener, M. M. & Husain, S. (2006) Invasive aspergillosis in the recipients of liver retransplantation. Liver Transpl, 12, 1205–9.
Gayowski, T., Marino, I. R., Singh, N., Doyle, H., Wagener, M., Fung, J. J. & Starzl, T. E. (1998) Orthotopic liver Transplantation in high-risk patients: risk factors associated with mortality and infectious morbidity. Transplantation, 65, 499–504.
Paterson, D. L., Singh, N., Gayowski, T. & Marino, I. R. (1998) Pulmonary nodules in liver transplant recipients. Medicine (Baltimore), 77, 50–8.
Paterson, D. L. & Singh, N. (1999) Invasive aspergillosis in transplant recipients. Medicine (Baltimore), 78, 123–38.
Helmi, M., Love, R. B., Welter, D., Cornwell, R. D. & Meyer, K. C. (2003) Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients. Chest, 123, 800–88.
Husain, S., Paterson, D. L., Studer, S., Pilewski, J., Crespo, M., Zaldonis, D., Shutt, K., Pakstis, D. L., Zeevi, A., Johnson, B., Kwak, E. J. & Mccurry, K. R. (2006) Voriconazole prophylaxis in lung transplant recipients. Am J Transplant, 6, 3008–16.
Kramer, M. R., Denning, D. W., Marshall, S. E., Ross, D. J., Berry, G., Lewiston, N. J., Stevens, D. A. & Theodore, J. (1991) Ulcerative tracheobronchitis after lung transplantation. A new form of invasive aspergillosis. Am Rev Respir Dis, 144, 552–56.
Singh, N., Arnow, P. M., Bonham, A., Dominguez, E., Paterson, D. L., Pankey, G. A., Wagener, M. M. & Yu, V. L. (1997) Invasive aspergillosis in liver transplant recipients in the 1990s. Transplantation, 64, 716–20.
Singh, N., Avery, R. K., Munoz, P., Pruett, T. L., Alexander, B., Jacobs, R., Tollemar, J. G., Dominguez, E. A., Yu, C. M., Paterson, D. L., Husain, S., Kusne, S. & Linden, P. (2003) Trends in risk profiles for and mortality associated with invasive aspergillosis among liver transplant recipients. Clin Infect Dis, 36, 46–52.
Rasmussen, C., Garen, C., Brining, S., Kincaid, R. L., Means, R. L. & Means, A. R. (1994) The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans. EMBO J, 13, 2545–52.
Singh, N. & Heitman, J. (2004) Antifungal attributes of immunosuppressive agents: new paradigms in management and elucidating the pathophysiologic basis of opportunistic mycoses in organ transplant recipients. Transplantation, 77, 795–800.
Kontoyiannis, D. P., Lewis, R. E., Osherov, N., Albert, N. D. & May, G. S. (2003) Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J Antimicrob Chemother, 51, 313–16.
Munoz, P., Alcala, L., Sanchez Conde, M., Palomo, J., Yanez, J., Pelaez, T. & Bouza, E. (2003) The isolation of Aspergillus fumigatus from respiratory tract specimens in heart transplant recipients is highly predictive of invasive aspergillosis. Transplantation, 75, 326–29.
Grossi, P., Farina, C., Fiocchi, R. & Dalla Gasperina, D. (2000) Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients. Transplantation, 70, 112–16.
Kusne, S., Torre-Cisneros, J., Manez, R., Irish, W., Martin, M., Fung, J., Simmons, R. L. & Starzl, T. E. (1992) Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation. J Infect Dis, 166, 1379–83.
Perfect, J. R., Cox, G. M., Lee, J. Y., Kauffman, C. A., De Repentigny, L., Chapman, S. W., Morrison, V. A., Pappas, P., Hiemenz, J. W. & Stevens, D. A. (2001) The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis. Clin Infect Dis, 33, 1824–33.
Weiland, D., Ferguson, R. M., Peterson, P. K., Snover, D. C., Simmons, R. L. & Najarian, J. S. (1983) Aspergillosis in 25 renal transplant patients. Epidemiology, clinical presentation, diagnosis, and management. Ann Surg, 198, 622–29.
Brown, R. S., JR., Lake, J. R., Katzman, B. A., Ascher, N. L., Somberg, K. A., Emond, J. C. & Roberts, J. P. (1996) Incidence and significance of Aspergillus cultures following liver and kidney Transplantation. Transplantation, 61, 666–69.
Fortun, J., Martin-Davila, P., Alvarez, M. E., Sanchez-Sousa, A., Quereda, C., Navas, E., Barcena, R., Vicente, E., Candelas, A., Honrubia, A., Nuno, J., Pintado, V. & Moreno, S. (2001) Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. Transplantation, 71, 145–49.
Kwak, E. J., Husain, S., Obman, A., Meinke, L., Stout, J., Kusne, S., Wagener, M. M. & Singh, N. (2004) Efficacy of galactomannan antigen in the Platelia Aspergillus enzyme immunoassay for diagnosis of invasive aspergillosis in liver transplant recipients. J Clin Microbiol, 42, 435–38.
Pfeiffer, C. D., Fine, J. P. & Safdar, N. (2006) Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis, 42, 1417–27.
Husain, S., Paterson, D. L., Studer, S. M., Crespo, M., Pilewski, J., Durkin, M., Wheat, J. L., Johnson, B., Mclaughlin, L., Bentsen, C., Mccurry, K. R. & Singh, N. (2007) Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation, 83, 1330–36.
Clancy, C. J., Jaber, R. A., Leather, H. L., Wingard, J. R., Staley, B., Wheat, L. J., Cline, C. L., Rand, K. H., Schain, D., Baz, M. & Nguyen, M. H. (2007) Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol, 45, 1759–65.
Pasqualotto, A. C. & Sukiennik, T. C. (2008) Beta-glucan in the diagnosis of invasive fungal disease. Clin Infect Dis, 47, 292–3; author reply 3–4.
Yoshida, M., Obayashi, T., Iwama, A., Ito, M., Tsunoda, S., Suzuki, T., Muroi, K., Ohta, M., Sakamoto, S. & Miura, Y. (1997) Detection of plasma (1 –> 3)-beta-D-glucan in patients with Fusarium, Trichosporon, Saccharomyces and Acremonium fungaemias. J Med Vet Mycol, 35, 371–4.
Ascioglu, S., Rex, J. H., De Pauw, B., Bennett, J. E., Bille, J., Crokaert, F., Denning, D. W., Donnelly, J. P., Edwards, J. E., Erjavec, Z., Fiere, D., Lortholary, O., Maertens, J., Meis, J. F., Patterson, T. F., Ritter, J., Selleslag, D., Shah, P. M., Stevens, D. A. & Walsh, T. J. (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis, 34, 7–14.
Akamatsu, N., Sugawara, Y., Kaneko, J., Tamura, S. & Makuuchi, M. (2007) Preemptive treatment of fungal Infection based on plasma (1 –> 3)beta-D-glucan levels after liver transplantation. Infection, 35, 346–51.
Singh, N. (2003) Treatment of opportunistic mycoses: how long is long enough? Lancet Infect Dis, 3, 703–8.
Herbrecht, R., Denning, D. W., Patterson, T. F., Bennett, J. E., Greene, R. E., Oestmann, J. W., Kern, W. V., Marr, K. A., Ribaud, P., Lortholary, O., Sylvester, R., Rubin, R. H., Wingard, J. R., Stark, P., Durand, C., Caillot, D., Thiel, E., Chandrasekar, P. H., Hodges, M. R., Schlamm, H. T., Troke, P. F. & De Pauw, B. (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med, 347, 408–15.
Marty, F. M., Lowry, C. M., Cutler, C. S., Campbell, B. J., Fiumara, K., Baden, L. R. & Antin, J. H. (2006) Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant, 12, 552–59.
Pascual, A., Calandra, T., Bolay, S., Buclin, T., Bille, J. & Marchetti, O. (2008) Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clin Infect Dis, 46, 201–11.
Smith, J., Safdar, N., Knasinski, V., Simmons, W., Bhavnani, S. M., Ambrose, P. G. & Andes, D. (2006) Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother, 50, 1570–72.
Tan, K., Brayshaw, N., Tomaszewski, K., Troke, P. & Wood, N. (2006) Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol, 46, 235–43.
Monforte, V., Roman, A., Gavalda, J., Bravo, C., Tenorio, L., Ferrer, A., Maestre, J. & Morell, F. (2001) Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant, 20, 1274–81.
Corcoran, T. E., Venkataramanan, R., Mihelc, K. M., Marcinkowski, A. L., Ou, J., Mccook, B. M., Weber, L., Carey, M. E., Paterson, D. L., Pilewski, J. M., Mccurry, K. R. & Husain, S. (2006) Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients. Am J Transplant, 6, 2765–73.
Drew, R. H., Dodds Ashley, E., Benjamin, D. K., JR., Duane Davis, R., Palmer, S. M. & Perfect, J. R. (2004) Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation, 77, 232–37.
Lowry, C. M., Marty, F. M., Vargas, S. O., Lee, J. T., Fiumara, K., Deykin, A. & Baden, L. R. (2007) Safety of aerosolized liposomal versus deoxycholate amphotericin B formulations for prevention of invasive fungal infections following lung transplantation: a retrospective study. Transpl Infect Dis, 9, 121–25.
Singh, N., Limaye, A. P., Forrest, G., Safdar, N., Munoz, P., Pursell, K., Houston, S., Rosso, F., Montoya, J. G., Patton, P., Del Busto, R., Aguado, J. M., Fisher, R. A., Klintmalm, G. B., Miller, R., Wagener, M. M., Lewis, R. E., Kontoyiannis, D. P. & Husain, S. (2006) Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation, 81, 320–26.
Singh, N., Wagener, M. M., Cacciarelli, T. V. & Levitsky, J. (2008) Antifungal management practices in liver transplant recipients. Am J Transplant, 8, 426–31.
Dummer, J. S., Lazariashvilli, N., Barnes, J., Ninan, M. & Milstone, A. P. (2004) A survey of anti-fungal management in lung transplantation. J Heart Lung Transplant, 23, 1376–81.
Husain, S., Zaldonis, D., Kusne, S., Kwak, E. J., Paterson, D. L. & Mccurry, K. R. (2006) Variation in antifungal prophylaxis strategies in lung transplantation. Transpl Infect Dis, 8, 213–18.
Tollemar, J., Hockerstedt, K., Ericzon, B. G., Jalanko, H. & Ringden, O. (1995) Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study. Transplantation, 59, 45–50.
Lorf, T., Braun, F., Ruchel, R., Muller, A., Sattler, B. & Ringe, B. (1999) Systemic Mycoses during prophylactical use of liposomal amphotericin B (Ambisome) after liver transplantation. Mycoses, 42, 47–53.
Singh, N., Paterson, D. L., Gayowski, T., Wagener, M. M. & Marino, I. R. (2001) Preemptive prophylaxis with a lipid preparation of amphotericin B for invasive fungal infections in liver transplant recipients requiring renal replacement therapy. Transplantation, 71, 910–13.
Fortun, J., Martin-Davila, P., Moreno, S., Barcena, R., De Vicente, E., Honrubia, A., Garcia, M., Nuno, J., Candela, A., Uriarte, M. & Pintado, V. (2003) 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, 813–19.
Calvo, V., Borro, J. M., Morales, P., Morcillo, A., Vicente, R., Tarrazona, V. & Paris, F. (1999) Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Transplant Group. Chest, 115, 1301–04.
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Silveira, F.P., Husain, S. (2009). Invasive Pulmonary Aspergillosis in Solid Organ Transplant Recipients. In: Comarú Pasqualotto, A. (eds) Aspergillosis: From Diagnosis to Prevention. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2408-4_34
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