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Semin Respir Crit Care Med 2011; 32(6): 717-726
DOI: 10.1055/s-0031-1295719
© Thieme Medical Publishers

Antifungal Prophylaxis in Lung Transplantation

Robin K. Avery1
  • 1Department of Infectious Disease, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
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Publication History

Publication Date:
13 December 2011 (online)

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ABSTRACT

Fungal infections are among the most serious complications of lung transplantation. The 1-year cumulative incidence of invasive fungal infections in lung transplant recipients is 6 to 10%, which is higher than most other solid organ transplant recipients. Aspergillus spp. are the most common etiologic agents, but Candida spp., non-Aspergillus mycelial fungi, Cryptococcus, Pneumocystis, and endemic mycoses can cause active infections in this population. Clinical manifestations of fungal infection in lung transplant recipients are protean, and include invasive pulmonary disease, airway and anastomotic infections, posttransplant empyemas, and disseminated infections. Most centers employ either universal or targeted antifungal prophylaxis in some form, but the agents, doses, durations, and monitoring strategies vary widely from one center to another. This review discusses the salient fungal organisms responsible for infection in lung transplant recipients and management strategies for prevention.

KEYWORDS

Fungal prophylaxis - aspergillosis - mold infection - invasive fungal infections - lung transplant

REFERENCES

  • 1 Singh N, Husain S. AST Infectious Diseases Community of Practice . Invasive aspergillosis in solid organ transplant recipients.  Am J Transplant. 2009;  9 (Suppl 4) S180-S191
    Search in Google Scholar
  • 2 Husain S, Paterson D L, Studer S et al.. Voriconazole prophylaxis in lung transplant recipients.  Am J Transplant. 2006;  6 (12) 3008-3016
    Search in Google Scholar
  • 3 Husain S, Mooney M L, Danziger-Isakov L et al.. A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients.  J Heart Lung Transplant. 2011;  30 (4) 361-374
    Search in Google Scholar
  • 4 Kubak B M. Fungal infection in lung transplantation.  Transpl Infect Dis. 2002;  4 (Suppl 3) 24-31
    Search in Google Scholar
  • 5 Danziger-Isakov L A, Worley S, Arrigain S et al.. Increased mortality after pulmonary fungal infection within the first year after pediatric lung transplantation.  J Heart Lung Transplant. 2008;  27 (6) 655-661
    Search in Google Scholar
  • 6 Pappas P G, Alexander B D, Andes D R et al.. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET).  Clin Infect Dis. 2010;  50 (8) 1101-1111
    Search in Google Scholar
  • 7 Husain S, Zaldonis D, Kusne S, Kwak E J, Paterson D L, McCurry K R. Variation in antifungal prophylaxis strategies in lung transplantation.  Transpl Infect Dis. 2006;  8 (4) 213-218
    Search in Google Scholar
  • 8 Neoh C F, Snell G I, Kotsimbos T et al.. Antifungal prophylaxis in lung transplantation—a world-wide survey.  Am J Transplant. 2011;  11 (2) 361-366
    Search in Google Scholar
  • 9 Singh N, Husain S. Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.  J Heart Lung Transplant. 2003;  22 (3) 258-266
    Search in Google Scholar
  • 10 Husni R N, Gordon S M, Longworth D L et al.. Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients.  Clin Infect Dis. 1998;  26 (3) 753-755
    Search in Google Scholar
  • 11 Cahill B C, Hibbs J R, Savik K et al.. Aspergillus airway colonization and invasive disease after lung transplantation.  Chest. 1997;  112 (5) 1160-1164
    Search in Google Scholar
  • 12 Flume P A, Egan T M, Paradowski L J, Detterbeck F C, Thompson J T, Yankaskas J R. Infectious complications of lung transplantation. Impact of cystic fibrosis.  Am J Respir Crit Care Med. 1994;  149 (6) 1601-1607
    Search in Google Scholar
  • 13 Husain S. Unique characteristics of fungal infections in lung transplant recipients.  Clin Chest Med. 2009;  30 (2) 307-313, vii
    Search in Google Scholar
  • 14 Choong C K, Sweet S C, Zoole J B et al.. Bronchial airway anastomotic complications after pediatric lung transplantation: incidence, cause, management, and outcome.  J Thorac Cardiovasc Surg. 2006;  131 (1) 198-203
    Search in Google Scholar
  • 15 Cuellar-Rodriguez J, Avery R K, Lard M et al.. Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area.  Clin Infect Dis. 2009;  49 (5) 710-716
    Search in Google Scholar
  • 16 Hadjiliadis D, Sporn T A, Perfect J R, Tapson V F, Davis R D, Palmer S M. Outcome of lung transplantation in patients with mycetomas.  Chest. 2002;  121 (1) 128-134
    Search in Google Scholar
  • 17 Weigt S S, Elashoff R M, Huang C et al.. Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome.  Am J Transplant. 2009;  9 (8) 1903-1911
    Search in Google Scholar
  • 18 Estenne M, Maurer J R, Boehler A et al.. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria.  J Heart Lung Transplant. 2002;  21 (3) 297-310
    Search in Google Scholar
  • 19 Valentine V G, Gupta M R, Walker Jr J E et al.. Effect of etiology and timing of respiratory tract infections on development of bronchiolitis obliterans syndrome.  J Heart Lung Transplant. 2009;  28 (2) 163-169
    Search in Google Scholar
  • 20 Valentine V G, Bonvillain R W, Gupta M R et al.. Infections in lung allograft recipients: ganciclovir era.  J Heart Lung Transplant. 2008;  27 (5) 528-535
    Search in Google Scholar
  • 21 Liu M, Worley S, Mallory Jr G B et al.. Fungal infections in pediatric lung transplant recipients: colonization and invasive disease.  J Heart Lung Transplant. 2009;  28 (11) 1226-1230
    Search in Google Scholar
  • 22 Luong M L, Morrissey O, Husain S. Assessment of infection risks prior to lung transplantation.  Curr Opin Infect Dis. 2010;  23 (6) 578-583
    Search in Google Scholar
  • 23 Issa N C, Fishman J A. Infectious complications of antilymphocyte therapies in solid organ transplantation.  Clin Infect Dis. 2009;  48 (6) 772-786
    Search in Google Scholar
  • 24 Peddi V R, Hariharan S, Schroeder T J, First M R. Role of granulocyte colony stimulating factor (G-CSF) in reversing neutropenia in renal allograft recipients.  Clin Transplant. 1996;  10 (1 Pt 1) 20-23
    Search in Google Scholar
  • 25 Palmer S M, Limaye A P, Banks M et al.. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial.  Ann Intern Med. 2010;  152 (12) 761-769
    Search in Google Scholar
  • 26 Goldfarb N S, Avery R K, Goormastic M et al.. Hypogammaglobulinemia in lung transplant recipients.  Transplantation. 2001;  71 (2) 242-246
    Search in Google Scholar
  • 27 Jordan S C, Toyoda M, Kahwaji J, Vo A A. Clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients.  Am J Transplant. 2011;  11 (2) 196-202
    Search in Google Scholar
  • 28 Husain S, Raza K, Pilewski J M et al.. Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.  Transplantation. 2009;  87 (12) 1852-1857
    Search in Google Scholar
  • 29 Kanj S S, Tapson V, Davis R D, Madden J, Browning I. Infections in patients with cystic fibrosis following lung transplantation.  Chest. 1997;  112 (4) 924-930
    Search in Google Scholar
  • 30 Gordon S M, LaRosa S P, Kalmadi S et al.. Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued?.  Clin Infect Dis. 1999;  28 (2) 240-246
    Search in Google Scholar
  • 31 Palmer S M, Perfect J R, Howell D N et al.. Candidal anastomotic infection in lung transplant recipients: successful treatment with a combination of systemic and inhaled antifungal agents.  J Heart Lung Transplant. 1998;  17 (10) 1029-1033
    Search in Google Scholar
  • 32 Hadjiliadis D, Howell D N, Davis R D et al.. Anastomotic infections in lung transplant recipients.  Ann Transplant. 2000;  5 (3) 13-19
    Search in Google Scholar
  • 33 Horvath J, Dummer S, Loyd J, Walker B, Merrill W H, Frist W H. Infection in the transplanted and native lung after single lung transplantation.  Chest. 1993;  104 (3) 681-685
    Search in Google Scholar
  • 34 Dowling R D, Baladi N, Zenati M et al.. Disruption of the aortic anastomosis after heart-lung transplantation.  Ann Thorac Surg. 1990;  49 (1) 118-122
    Search in Google Scholar
  • 35 Hamacher J, Spiliopoulos A, Kurt A M, Nicod L P. Geneva Lung Transplantation Group . Pre-emptive therapy with azoles in lung transplant patients.  Eur Respir J. 1999;  13 (1) 180-186
    Search in Google Scholar
  • 36 Minari A, Husni R, Avery R K et al.. The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants.  Transpl Infect Dis. 2002;  4 (4) 195-200
    Search in Google Scholar
  • 37 Hosseini-Moghaddam S M, Husain S. Fungi and molds following lung transplantation.  Semin Respir Crit Care Med. 2010;  31 (2) 222-233
    Search in Google Scholar
  • 38 Husain S, Alexander B D, Munoz P et al.. Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi.  Clin Infect Dis. 2003;  37 (2) 221-229
    Search in Google Scholar
  • 39 Costa S F, Alexander B D. Non-Aspergillus fungal pneumonia in transplant recipients.  Clin Chest Med. 2005;  26 (4) 675-690, vii
    Search in Google Scholar
  • 40 Sahi H, Avery R K, Minai O A et al.. Scedosporium apiospermum (Pseudoallescheria boydii) infection in lung transplant recipients.  J Heart Lung Transplant. 2007;  26 (4) 350-356
    Search in Google Scholar
  • 41 Das A, MacLaughlin E F, Ross L A et al.. Paecilomyces variotii in a pediatric patient with lung transplantation.  Pediatr Transplant. 2000;  4 (4) 328-332
    Search in Google Scholar
  • 42 Lee J, Yew W W, Chiu C S, Wong P C, Wong C F, Wang E P. Delayed sternotomy wound infection due to Paecilomyces variotii in a lung transplant recipient.  J Heart Lung Transplant. 2002;  21 (10) 1131-1134
    Search in Google Scholar
  • 43 Tamm M, Malouf M, Glanville A. Pulmonary scedosporium infection following lung transplantation.  Transpl Infect Dis. 2001;  3 (4) 189-194
    Search in Google Scholar
  • 44 Ambrosioni J, Bouchuiguir-Wafa K, Garbino J. Emerging invasive zygomycosis in a tertiary care center: epidemiology and associated risk factors.  Int J Infect Dis. 2010 14 (Suppl 3) e100-103
  • 45 Silveira F P, Kwak E J, Paterson D L, Pilewski J M, McCurry K R, Husain S. Post-transplant colonization with non-Aspergillus molds and risk of development of invasive fungal disease in lung transplant recipients.  J Heart Lung Transplant. 2008;  27 (8) 850-855
    Search in Google Scholar
  • 46 Singh N, Forrest G. AST Infectious Diseases Community of Practice . Cryptococcosis in solid organ transplant recipients.  Am J Transplant. 2009;  9 (Suppl 4) S192-S198
    Search in Google Scholar
  • 47 Singh N, Alexander B D, Lortholary O et al.. Pulmonary cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen.  Clin Infect Dis. 2008;  46 (2) e12-e18
    Search in Google Scholar
  • 48 Singh N, Lortholary O, Alexander B D Cryptococcal Collaborative Transplant Study Group et al. An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.  Clin Infect Dis. 2005;  40 (12) 1756-1761
    Search in Google Scholar
  • 49 Kontoyiannis D P, Lewis R E, Alexander B D et al.. Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis.  Antimicrob Agents Chemother. 2008;  52 (2) 735-738
    Search in Google Scholar
  • 50 Miller M B, Hendren R, Gilligan P H. Posttransplantation disseminated coccidioidomycosis acquired from donor lungs.  J Clin Microbiol. 2004;  42 (5) 2347-2349
    Search in Google Scholar
  • 51 Tripathy U, Yung G L, Kriett J M, Thistlethwaite P A, Kapelanski D P, Jamieson S W. Donor transfer of pulmonary coccidioidomycosis in lung transplantation.  Ann Thorac Surg. 2002;  73 (1) 306-308
    Search in Google Scholar
  • 52 Perfect J R, Dodds Ashley E, Drew R. Design of aerosolized amphotericin b formulations for prophylaxis trials among lung transplant recipients.  Clin Infect Dis. 2004;  39 (Suppl 4) S207-S210
    Search in Google Scholar
  • 53 Borro J M, Solé A, de la Torre M et al.. Efficiency and safety of inhaled amphotericin B lipid complex (Abelcet) in the prophylaxis of invasive fungal infections following lung transplantation.  Transplant Proc. 2008;  40 (9) 3090-3093
    Search in Google Scholar
  • 54 Palmer S M, Drew R H, Whitehouse J D et al.. Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.  Transplantation. 2001;  72 (3) 545-548
    Search in Google Scholar
  • 55 Reichenspurner H, Gamberg P, Nitschke M et al.. Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis.  Transplant Proc. 1997;  29 (1-2) 627-628
    Search in Google Scholar
  • 56 Drew R H, Dodds Ashley E, Benjamin Jr D K, Duane Davis R, Palmer S M, Perfect J R. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.  Transplantation. 2004;  77 (2) 232-237
    Search in Google Scholar
  • 57 Lowry C M, Marty F M, Vargas S O et al.. Safety of aerosolized liposomal versus deoxycholate amphotericin B formulations for prevention of invasive fungal infections following lung transplantation: a retrospective study.  Transpl Infect Dis. 2007;  9 (2) 121-125
    Search in Google Scholar
  • 58 Corcoran T E, Venkataramanan R, Mihelc K M et al.. Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients.  Am J Transplant. 2006;  6 (11) 2765-2773
    Search in Google Scholar
  • 59 Monforte V, Ussetti P, López R et al.. Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety.  J Heart Lung Transplant. 2009;  28 (2) 170-175
    Search in Google Scholar
  • 60 Husain S, Capitano B, Corcoran T et al.. Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients.  Transplantation. 2010;  90 (11) 1215-1219
    Search in Google Scholar
  • 61 Monforte V, Román A, Gavaldà J et al.. Contamination of the nebulization systems used in the prophylaxis with amphotericin B nebulized in lung transplantation.  Transplant Proc. 2005;  37 (9) 4056-4058
    Search in Google Scholar
  • 62 Shitrit D, Ollech J E, Ollech A et al.. Itraconazole prophylaxis in lung transplant recipients receiving tacrolimus (FK 506): efficacy and drug interaction.  J Heart Lung Transplant. 2005;  24 (12) 2148-2152
    Search in Google Scholar
  • 63 Han K, Capitano B, Bies R et al.. Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients.  Antimicrob Agents Chemother. 2010;  54 (10) 4424-4431
    Search in Google Scholar
  • 64 Cadena J, Levine D J, Angel L F et al.. Antifungal prophylaxis with voriconazole or itraconazole in lung transplant recipients: hepatotoxicity and effectiveness.  Am J Transplant. 2009;  9 (9) 2085-2091
    Search in Google Scholar
  • 65 Mattner F, Chaberny I F, Weissbrodt H et al.. [Surveillance of invasive mold infections in lung transplant recipients: effect of antimycotic prophylaxis with itraconazole and voriconazole].  Mycoses. 2005;  48 (Suppl 1) 51-55
    Search in Google Scholar
  • 66 Mattner F, Weissbrodt H, Strueber M. Two case reports: fatal Absidia corymbifera pulmonary tract infection in the first postoperative phase of a lung transplant patient receiving voriconazole prophylaxis, and transient bronchial Absidia corymbifera colonization in a lung transplant patient.  Scand J Infect Dis. 2004;  36 (4) 312-314
    Search in Google Scholar
  • 67 Calvo V, Borro J M, Morales P Valencia Lung Transplant Group et al. Antifungal prophylaxis during the early postoperative period of lung transplantation.  Chest. 1999;  115 (5) 1301-1304
    Search in Google Scholar
  • 68 Eriksson M, Lemström K, Suojaranta-Ylinen R et al.. Control of early Aspergillus mortality after lung transplantation: outcome and risk factors.  Transplant Proc. 2010;  42 (10) 4459-4464
    Search in Google Scholar
  • 69 Boehler A, Vogt P, Zollinger A, Weder W, Speich R. Prospective study of the value of transbronchial lung biopsy after lung transplantation.  Eur Respir J. 1996;  9 (4) 658-662
    Search in Google Scholar
  • 70 Silveira F P, Husain S. Fungal infections in lung transplant recipients.  Curr Opin Pulm Med. 2008;  14 (3) 211-218
    Search in Google Scholar

Robin K AveryM.D. 

Department of Infectious Disease, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

9500 Euclid Ave., Desk G-21, Cleveland OH 44195

Email: averyr@ccf.org