Risks and Epidemiology of Infections After Lung or Heart–Lung Transplantation

Chapter

Abstract

Nowadays, lung transplantation is an established treatment option of end-stage pulmonary parenchymal and vascular disease. Post-transplant infections are a significant contributor to overall morbidity and mortality in the lung transplant recipient that, in turn, are higher than in other solid organ transplant recipients. This is likely due to several specific factors such as the constant exposure to the outside environment and the colonized native airway, and the disruption of usual mechanisms of defense including the cough reflex, bronchial circulation, and lymphatic drainage. This chapter will review the common infections that develop in the lung or heart–lung transplant recipient, including the general risk factors for infection in this population, and specific features of prophylaxis and treatment for the most frequent bacterial, viral, and fungal infections. The effects of infection on lung transplant rejection will also be discussed.

Keywords

Lung transplantation Heart transplantation Immunosuppression Bacterial infection Cytomegalovirus Respiratory viruses Aspergillus 

References

  1. 1.
    Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med. 1999;340:1081–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Webber SA, McCurry K, Zeevi A. Heart and lung transplantation in children. Lancet. 2006;368:53–69.PubMedCrossRefGoogle Scholar
  3. 3.
    Pierson III RN. Lung transplantation: current status and challenges. Transplantation. 2006;81:1609–15.PubMedCrossRefGoogle Scholar
  4. 4.
    Liou TG, Woo MS, Cahill BC. Lung transplantation for cystic fibrosis. Curr Opin Pulm Med. 2006;12:459–63.PubMedCrossRefGoogle Scholar
  5. 5.
    Mendeloff EN, Meyers BF, Sundt TM, et al. Lung transplantation for pulmonary vascular disease. Ann Thorac Surg. 2002;73:209–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Yusen RD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report—2014; focus theme: retransplantation. J Heart Lung Transplant. 2014;33:1009–24.PubMedCrossRefGoogle Scholar
  7. 7.
    Meyer KC, Raghu G, Verleden GM, et al. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014;44:1479–503.PubMedCrossRefGoogle Scholar
  8. 8.
    Weigt SS, DerHovanessian A, Wallace WD, Lynch 3rd JP, Belperio JA. Bronchiolitis obliterans syndrome: the Achilles’ heel of lung transplantation. Semin Respir Crit Care Med. 2013;34:336–51.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kumar D, Erdman D, Keshavjee S, et al. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant. 2005;5:2031–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Magnusson J, Westin J, Andersson LM, Brittain-Long R, Riise GC. The impact of viral respiratory tract infections on long-term morbidity and mortality following lung transplantation: a retrospective cohort study using a multiplex PCR panel. Transplantation. 2013;95:383–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Sato M, Waddell TK, Wagnetz U, et al. Restrictive allograft syndrome (RAS): a novel form of chronic lung allograft dysfunction. J Heart Lung Transplant. 2011;30:735–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Avery RK. Infections after lung transplantation. Semin Respir Crit Care Med. 2006;27:544–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Horvath J, Dummer S, Loyd J, et al. Infection in the transplanted and native lung after single lung transplantation. Chest. 1993;104:681–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Kramer MR, Marshall SE, Starnes VA, et al. Infectious complications in heart–lung transplantation: analysis of 200 episodes. Arch Intern Med. 1993;153:2010–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Maurer JR, Tullis DE, Grossman RF, et al. Infectious complications following isolated lung transplantation. Chest. 1992;101:1056–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Bando K, Paradis IL, Komatsu K, et al. Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation. J Thorac Cardiovasc Surg. 1995;109:49–57.PubMedCrossRefGoogle Scholar
  17. 17.
    Baz MA, Palmer SM, Staples ED, Greer DG, Tapson VF, Davis DD. Lung transplantation after long-term mechanical ventilation: results and 1-year follow-up. Chest. 2001;119:224–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Bartz RR, Love RB, Leverson GE, Will LR, Welter DL, Meyer KC. Pre-transplant mechanical ventilation and outcome in patients with cystic fibrosis. J Heart Lung Transplant. 2003;22:433–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Frias Perez MA, Ibarra de la Rosa I, Garcia ME, et al. [Invasive mechanical ventilation in cystic fibrosis: influence in lung transplant]. An Pediatr (Barc). 2009;71:128–34.CrossRefGoogle Scholar
  20. 20.
    Chan KM, Allen SA. Infectious pulmonary complications in lung transplant recipients. Semin Respir Infect. 2002;17:291–302.PubMedCrossRefGoogle Scholar
  21. 21.
    Schafers HJ, Wagner TO, Demertzis S, et al. Preoperative corticosteroids: a contraindication to lung transplantation? Chest. 1992;102:1522–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Venuta F, Boehler A, Rendina EA, et al. Complications in the native lung after single lung transplantation. Eur J Cardiothorac Surg. 1999;16:54–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Lowery EM, Bemiss B, Cascino T, et al. Low vitamin D levels are associated with increased rejection and infections after lung transplantation. J Heart Lung Transplant. 2012;31:700–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Fiser SM, Kron IL, Long SM, et al. Influence of graft ischemic time on outcomes following lung transplantation. J Heart Lung Transplant. 2001;20:1291–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Herve P, Silbert D, Cerrina J, et al. Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double lung transplantation: the Paris-Sud Lung Transplant Group. Chest. 1993;103:59–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Paradis IL, Marrari M, Zeevi A, et al. HLA phenotype of lung lavage cells following heart-lung transplantation. J Heart Transplant. 1985;4:422–5.PubMedGoogle Scholar
  27. 27.
    Zenati M, Dowling RD, Dummer JS, et al. Influence of the donor lung on development of early infections in lung transplant recipients. J Heart Transplant. 1990;9:50–8.Google Scholar
  28. 28.
    Ruiz I, Gavaldà J, Monforte V, et al. Donor-to-host transmission of bacterial and fungal infections in lung transplantation. Am J Transplant. 2006;6:178–82.PubMedCrossRefGoogle Scholar
  29. 29.
    Low DE, Kaiser LR, Haydock DA, et al. The donor lung: infectious and pathologic factors affecting outcome in lung transplantation. J Thorac Cardiovasc Surg. 1993;106:614–21.PubMedGoogle Scholar
  30. 30.
    Waller DA, Thompson AM, Wrightson WN, et al. Does the mode of donor death influence the early outcome of lung transplantation? A review of lung transplantation from donors involved in major trauma. J Heart Lung Transplant. 1995;14:318–21.PubMedGoogle Scholar
  31. 31.
    Len O, Garzoni C, Lumbreras C, et al. Recommendations for screening of donor and recipient prior to solid organ transplantation and to minimize transmission of donor-derived infections. Clin Microbiol Infect. 2014;20 Suppl 7:10–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Snell GI, Griffiths A, Macfarlane L, et al. Maximizing thoracic organ transplant opportunities: the importance of efficient coordination. J Heart Lung Transplant. 2000;19:401–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Kamineni R, Lui CY, Copeland JG. Severe obstruction of the left main coronary artery by mycotic aortic pseudoaneurysm following orthotopic heart transplantation. J Heart Lung Transplant. 2004;23:499–502.PubMedCrossRefGoogle Scholar
  34. 34.
    Dowling RD, Zenati M, Yousem SA, et al. Donor-transmitted pneumonia in experimental lung allografts. successful prevention with donor antibiotic therapy. J Thorac Cardiovasc Surg. 1992;103:767–72.PubMedGoogle Scholar
  35. 35.
    Walter S, Gudowius P, Bosshammer J, et al. Epidemiology of chronic Pseudomonas aeruginosa infections in the airways of lung transplant recipients with cystic fibrosis. Thorax. 1997;52:318–21.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Silveira FP, Husain S. Fungal infections in lung transplant recipients. Curr Opin Pulm Med. 2008;14:211–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Aris RM, Routh JC, LiPuma JJ, et al. Lung transplantation for cystic fibrosis patients with Burkholderia cepacia complex: survival linked to genomovar type. Am J Respir Crit Care Med. 2001;164:2102–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Chaparro C, Maurer J, Gutierrez C, et al. Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation. Am J Respir Crit Care Med. 2001;163:43–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Heath DG, Hohneker K, Carriker C, et al. Six-year molecular analysis of Burkholderia cepacia complex isolates among cystic fibrosis patients at a referral center for lung transplantation. J Clin Microbiol. 2002;40:1188–93.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Sun L, Jiang RZ, Steinbach S, et al. The emergence of a highly transmissible lineage of cbl + Pseudomonas (Burkholderia) cepacia causing CF centre epidemics in North America and Britain. Nat Med. 1995;1:661–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Boussaud V, Guillemain R, Grenet D, et al. Clinical outcome following lung transplantation in patients with cystic fibrosis colonized with Burkholderia cepacia complex: results from two French centers. Thorax. 2008;63:732–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Alexander BD, Petzold EW, Reller LB, et al. Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia cepacia complex. Am J Transplant. 2008;8:1025–30.PubMedCrossRefGoogle Scholar
  43. 43.
    Esther Jr CR, Esserman DA, Gilligan P, Kerr A, Noone PG. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis. J Cyst Fibros. 2010;9:117–23.PubMedCrossRefGoogle Scholar
  44. 44.
    Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015;34:1–15.PubMedCrossRefGoogle Scholar
  45. 45.
    Brock MV, Borja MC, Ferber L, et al. Induction therapy in lung transplantation: a prospective, controlled clinical trial comparing OKT3, anti-thymocyte globulin, and daclizumab. J Heart Lung Transplant. 2001;20:1282–90.PubMedCrossRefGoogle Scholar
  46. 46.
    Clinckart F, Bulpa P, Jamart J, et al. Basiliximab as an alternative to antithymocyte globulin for early immunosuppression in lung transplantation. Transplant Proc. 2009;41:607–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Treede H, Klepetko W, Reichenspurner H, et al. Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols. J Heart Lung Transplant. 2001;20:511–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Keenan RJ, Konishi H, Kawai A, et al. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg. 1995;60:580–4.PubMedCrossRefGoogle Scholar
  49. 49.
    Chambers DC, Davies B, Mathews A, Yerkovich ST, Hopkins PM. Bronchiolitis obliterans syndrome, hypogammaglobulinemia, and infectious complications of lung transplantation. J Heart Lung Transplant. 2013;32:36–43.PubMedCrossRefGoogle Scholar
  50. 50.
    Ohsumi A, Chen F, Yamada T, et al. Effect of hypogammaglobulinemia after lung transplantation: a single-institution study. Eur J Cardiothorac Surg. 2014;45:e61–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Lederer DJ, Philip N, Rybak D, Arcasoy SM, Kawut SM. Intravenous immunoglobulin for hypogammaglobulinemia after lung transplantation: a randomized crossover trial. PLoS One. 2014;9:e103908.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Fishman JA, Emery V, Freeman R, et al. Cytomegalovirus in transplantation—challenging the status quo. Clin Transplant. 2007;21:149–58.PubMedCrossRefGoogle Scholar
  53. 53.
    Remund KF, Best M, Egan JJ. Infections relevant to lung transplantation. Proc Am Thorac Soc. 2009;6:94–100.PubMedCrossRefGoogle Scholar
  54. 54.
    Speich R, van der Bij W. Epidemiology and management of infections after lung transplantation. Clin Infect Dis. 2001;33:S58–65.PubMedCrossRefGoogle Scholar
  55. 55.
    Luong ML, Morrissey O, Husain S. Assessment of infection risks prior to lung transplantation. Curr Opin Infect Dis. 2010;23:578–83.PubMedCrossRefGoogle Scholar
  56. 56.
    Gregson AL, Wang X, Weight SS, et al. Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation. Am J Respir Crit Care Med. 2013;187:518–26.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Dudau D, CAmous J, Marchand S, et al. Incidence of nosocomial pneumonia and risk of recurrence after antimicrobial therapy in critically ill lung and heart-lung transplant patients. Clin Transplant. 2014;28:27–36.PubMedCrossRefGoogle Scholar
  58. 58.
    Palacio F, Reyes LF, Levine DJ, et al. Understanding the concept of health care-associated pneumonia in lung transplant recipients. Chest. 2015;148:516–22.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Bui KT, Mehta S, Khuu TH, et al. Extended spectrum β-lactamase-producing Enterobacteriaceae infection in heart and lung transplant recipients and in mechanical circulatory support recipients. Transplantation. 2014;97:590–4.PubMedCrossRefGoogle Scholar
  60. 60.
    Riera J, Caralt B, Lopez I, et al. Ventilator-associated respiratory infection following lung transplantation. Eur Respir J. 2015;45:726–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Aguilar-Guisado M, Gavaldá J, Ussetti P, et al. Pneumonia after lung transplantation in the RESITRA cohort: a multicenter prospective study. Am J Transplant. 2007;7:1989–96.PubMedCrossRefGoogle Scholar
  62. 62.
    Shields RK, Clancy CJ, Minces LR, et al. Epidemiology and outcomes of deep surgical site infections following lung transplantation. Am J Transplant. 2013;13:2137–45.PubMedCrossRefGoogle Scholar
  63. 63.
    Husain S, Chan KM, Palmer SM, et al. Bacteremia in lung transplant recipients in the current era. Am J Transplant. 2006;6:3000–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Mortensen E, Hellinger W, Keller C, et al. Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention. Transpl Infect Dis. 2014;16:67–75.PubMedCrossRefGoogle Scholar
  65. 65.
    Bravo C, Roldán J, Roman A, et al. Tuberculosis in lung transplant recipients. Transplantation. 2005;79:59–64.PubMedCrossRefGoogle Scholar
  66. 66.
    Knoll BM, Kappagoda S, Gill RR, et al. Non-tuberculous mycobacterial infection among lung transplant recipients: a 15-year cohort study. Transpl Infect Dis. 2012;14:452–60.PubMedCrossRefGoogle Scholar
  67. 67.
    Huang HC, Weigt SS, Derhovanessian A, et al. Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality. J Heart Lung Transplant. 2011;30:790–8.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Longworth SA, Vinnard C, Lee I, Sims KD, Barton TD, Blumberg EA. Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case-control study. Transpl Infect Dis. 2014;16:76–83.PubMedCrossRefGoogle Scholar
  69. 69.
    Chernenko SM, Humar A, Hutcheon M, et al. Mycobacterium abscessus infections in lung transplant recipients: the international experience. J Heart Lung Transplant. 2006;25:1447–55.PubMedCrossRefGoogle Scholar
  70. 70.
    Roberts SA, Franklin JC, Mijch A, et al. Nocardia infection in heart–lung transplant recipients at Alfred Hospital, Melbourne, Australia, 1989–1998. Clin Infect Dis. 2000;31:968–72.PubMedCrossRefGoogle Scholar
  71. 71.
    Khan BA, Duncan M, Reynolds J, et al. Nocardia infection in lung transplant recipients. Clin Transplant. 2008;22:562–6.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Lee JT, Hertz MI, Dunitz JM, et al. The rise of Clostridium difficile infection in lung transplant recipients in the modern era. Clin Transplant. 2013;27:303–10.PubMedCrossRefGoogle Scholar
  73. 73.
    Len O, Rodriguez-Pardo D, Gavalda J, et al. Outcome of Clostridium difficile-associated disease in solid organ transplant recipients: a prospective and multicenter cohort study. Transpl Int. 2012;25:1275–81.PubMedCrossRefGoogle Scholar
  74. 74.
    Doligalski CT, Benedict K, Cleveland AA, et al. Epidemiology of invasive mold infections in lung transplant recipients. Am J Transplant. 2014;14:1328–33.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Mehrad B, Paciocco G, Martinez FJ, et al. Spectrum of Aspergillus infection in lung transplant recipients: case series and review of the literature. Chest. 2001;119:169–75.PubMedCrossRefGoogle Scholar
  76. 76.
    Gavalda J, Len O, San Juan R, et al. Risk factors for invasive aspergillosis in solid organ transplant recipients: a case-control study. Clin Infect Dis. 2005;41:52–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Chong PP, Kennedy CC, HathcocK MA, Kremers WK, Razonable RR. Epidemiology of invasive fungal infections in lung transplant recipients on long-term azole antifungal prophylaxis. Clin Transplant. 2015;29:311–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Grossi P, Farina C, Fiocchi R, Dalla GD. 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. 2000;70:112–6.PubMedGoogle Scholar
  79. 79.
    Cahill BC, Hibbs JR, Savik K, et al. Aspergillus airway colonization and invasive disease after lung transplantation. Chest. 1997;112:1160–4.PubMedCrossRefGoogle Scholar
  80. 80.
    Wójtowicz A, Gresnight MS, Lecompte T, et al. IL1B and DEFB1 polymorphisms increase susceptibility to invasive mold infection after solid-organ transplantation. J Infect Dis. 2015;211:1646–57.PubMedCrossRefGoogle Scholar
  81. 81.
    Weigt SS, Copeland CA, Derhovanessian A, et al. Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: a two-center validation study. Am J Transplant. 2013;13:919–27.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Kramer MR, Denning DW, Marshall SE, et al. Ulcerative tracheobronchitis after lung transplantation: a new form of invasive aspergillosis. Am Rev Respir Dis. 1991;144:552–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Nathan SD, Shorr AF, Schmidt ME, et al. Aspergillus and endobronchial abnormalities in lung transplant recipients. Chest. 2000;118:403–7.PubMedCrossRefGoogle Scholar
  84. 84.
    Husain S, Mooney ML, 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;30:361–74.PubMedCrossRefGoogle Scholar
  85. 85.
    Husain S, Paterson DL, Studer SM, et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation. 2007;83:1330–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Clancy CJ, Jaber RA, Leather HL, et al. Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary aspergillosis among solid-organ transplant recipients. J Clin Microbiol. 2007;45:1759–65.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Luong ML, Clancy CJ, Vadnerkar A, et al. Comparison of an Aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis. 2011;52:1218–26.PubMedCrossRefGoogle Scholar
  88. 88.
    Speziali G, McDougall JC, Midthun DE, et al. Native lung complications after single lung transplantation for emphysema. Transpl Int. 1997;10:113–5.PubMedCrossRefGoogle Scholar
  89. 89.
    Moreno A, Cervera C, Gavalda J, et al. Bloodstream infections among transplant recipients: results of a nationwide surveillance in Spain. Am J Transplant. 2007;7:2579–86.PubMedCrossRefGoogle Scholar
  90. 90.
    Palmer SM, Perfect JR, Howell DN, 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;17:1029–33.PubMedGoogle Scholar
  91. 91.
    Wang EH, Partovi N, Levy RD, Shapiro RJ, Yoshida EM, Greanya ED. Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past. Transpl Infect Dis. 2012;14:519–25.PubMedCrossRefGoogle Scholar
  92. 92.
    Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010;50:1101–11.PubMedCrossRefGoogle Scholar
  93. 93.
    Singh N, Alexander BD, Lortholary O, et al. Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality. J Infect Dis. 2007;195:756–64.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Datta K, Bartlett KH, Baer R, et al. Spread of Cryptococcus gattii into Pacific Northwest region of the United States. Emerg Infect Dis. 2009;15:1185–91.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Hagen F, Colom MF, Swinne D, et al. Autochthonous and dormant Cryptococcus gattii infections in Europe. Emerg Infect Dis. 2012;18:1618–24.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of America. Clin Infect Dis. 2010;50:291–322.PubMedCrossRefGoogle Scholar
  97. 97.
    Husain S, Wagener MM, Singh N. Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome. Emerg Infect Dis. 2001;7:375–81.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Cuenca-Estrella M, Bernal-Martinez L, Isla G, Gomez-Lopez A, Alcazar-Fuoli L, Buitrago MJ. Incidence of zygomycosis in transplant recipients. Clin Microbiol Infect. 2009;15 suppl 5:37–40.PubMedCrossRefGoogle Scholar
  99. 99.
    Carneiro HA, Coleman JJ, Restrepo A, Mylonakis E. Fusarium infection in lung transplant patients: report of 6 cases and review of the literature. Medicine (Baltimore). 2011;90:69–80.CrossRefGoogle Scholar
  100. 100.
    Lanternier F, Sun HY, Ribaud P, Singh N, Kontoyiannis DP, Lortholary O. Mucormycosis in organ and stem cell transplant recipients. Clin Infect Dis. 2012;54:1629–36.PubMedCrossRefGoogle Scholar
  101. 101.
    Singh N, Aguado JM, Bonatti H, et al. Zygomycosis in solid organ transplant recipients: a prospective, matched case-control study to assess risks for disease and outcome. J Infect Dis. 2009;200:1002–11.PubMedCrossRefGoogle Scholar
  102. 102.
    Sun HY, Forrest G, Gupta KL, et al. Rhino-orbital-cerebral zygomycosis in solid organ transplant recipients. Transplantation. 2010;90:85–92.PubMedCrossRefGoogle Scholar
  103. 103.
    Sole A, Salavert M. Fungal infections after lung transplantation. Curr Opin Pulm Med. 2009;15:243–53.PubMedCrossRefGoogle Scholar
  104. 104.
    Assi M, Martin S, Wheat LJ, et al. Histoplasmosis after solid organ transplant. Clin Infect Dis. 2013;57:1542–9.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Cuellar-Rodriguez J, Avery RK, 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;49:710–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Vikram HR, Dosanjh A, Blair JE. Coccidioidomycosis and lung transplantation. Transplantation. 2011;92:717–21.PubMedCrossRefGoogle Scholar
  107. 107.
    Gavaldà J, Meije Y, Fortún J, et al. Invasive fungal infections in solid organ transplant recipients. Clin Microbiol Infect. 2014;20 Suppl 7:27–48.PubMedCrossRefGoogle Scholar
  108. 108.
    Monforte V, Roman A, Gavalda J, et al. Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant. 2001;20:1274–81.PubMedCrossRefGoogle Scholar
  109. 109.
    Monforte V, Ussetti P, Lopez R, et al. Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant. 2009;28:170–5.PubMedCrossRefGoogle Scholar
  110. 110.
    Monforte V, Roman A, Gavalda J, et al. Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients. Transplantation. 2003;75:1571–4.PubMedCrossRefGoogle Scholar
  111. 111.
    Neoh CF, Snell GI, Levvey B, et al. Preemptive treatment with voriconazole in lung transplant recipients. Transpl Infect Dis. 2013;15:344–53.PubMedCrossRefGoogle Scholar
  112. 112.
    Luong ML, Hosseini-Moghaddam SM, Singer LG, et al. Risk factors for voriconazole hepatotoxicity at 12 weeks in lung transplant recipients. Am J Transplant. 2012;12:1929–35.PubMedCrossRefGoogle Scholar
  113. 113.
    Singer JP, Boker A, Metchnikoff C, et al. High cumulative dose exposure to voriconazole is associated with cutaneous squamous cell carcinoma in lung transplant recipients. J Heart Lung Transplant. 2012;31:694–9.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Zamora MR. Cytomegalovirus and lung transplantation. Am J Transplant. 2004;4:1219–26.PubMedCrossRefGoogle Scholar
  115. 115.
    Manuel O, Husain S, Kumar D, et al. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013;56:817–24.PubMedCrossRefGoogle Scholar
  116. 116.
    Cantisán S, Lara R, Montejo M, et al. Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant. 2013;13:738–45.PubMedCrossRefGoogle Scholar
  117. 117.
    Hooks MA, Perlino CA, Henderson JM, Millikan Jr WJ, Kutner MH. Prevalence of invasive cytomegalovirus disease with administration of muromonab CD-3 in patients undergoing orthotopic liver transplantation. Ann Pharmacother. 1992;26:617–20.PubMedCrossRefGoogle Scholar
  118. 118.
    Charpentier B, Rostaing L, Berthoux F, et al. A three-arm study comparing immediate tacrolimus therapy with antithymocyte globulin induction therapy followed by tacrolimus or cyclosporine A in adultrenal transplant recipients. Transplantation. 2003;75:844–51.PubMedCrossRefGoogle Scholar
  119. 119.
    Pescovitz MD. Benefits of cytomegalovirus prophylaxis in solid organ transplantation. Transplantation. 2006;82(2 suppl):S4–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Giulieri S, Manuel O. QuantiFERON(R)-CMV assay for the assessment of cytomegalovirus cell-mediated immunity. Expert Rev Mol Diagn. 2011;11:17–25.PubMedCrossRefGoogle Scholar
  121. 121.
    Snyder LD, Chan C, Kwon D et al. Polyfunctional T cell Responses Predict Protection from Cytomegalovirus After Lung Transplant. Am J Respir Crit Care Med. 2016;193(1):78-85.Google Scholar
  122. 122.
    Ghassemieh B, Ahya VN, Baz MA, et al. Decreased incidence of cytomegalovirus infection with sirolimus in a post hoc randomized, multicenter study in lung transplantation. J Heart Lung Transplant. 2013;32:701–6.PubMedCrossRefGoogle Scholar
  123. 123.
    DesJardin JA, Gibbons L, Cho E, et al. Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection. J Infect Dis. 1998;178:1783–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Fernandez-Ruiz M, Lopez-Medrano F, Varela-Peña P, et al. Monitoring of immunoglobulin levels identifies kidney transplant recipients at high risk of infection. Am J Transplant. 2012;12:2763–73.PubMedCrossRefGoogle Scholar
  125. 125.
    Kijpittayarit S, Eid AJ, Brown RA, Paya CV, Razonable RR. Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation. Clin Infect Dis. 2007;44:1315–20.PubMedCrossRefGoogle Scholar
  126. 126.
    Cervera C, Balderramo D, Suarez B, et al. Donor mannose-binding lectin gene polymorphisms influence the outcome of liver transplantation. Liver Transpl. 2009;15:1217–24.PubMedCrossRefGoogle Scholar
  127. 127.
    Michaelides A, Glare EM, Spelman DW, et al. β-Herpesvirus (human cytomegalovirus and human herpesvirus 6) reactivation in at-risk lung transplant recipients and in human immunodeficiency virus-infected patients. J Infect Dis. 2002;186:173–80.PubMedCrossRefGoogle Scholar
  128. 128.
    Milstone AP, Brumble LM, Loyd JE, et al. Active CMV infection before lung transplantation: risk factors and clinical implications. J Heart Lung Transplant. 2000;19:744–50.PubMedCrossRefGoogle Scholar
  129. 129.
    Michaelides A, Liolios L, Glare EM, et al. Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis. Transplantation. 2001;72:141–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Barber L, Egan JJ, Lomax J, et al. A prospective study of a quantitative PCR ELISA assay for the diagnosis of CMV pneumonia in lung and heart-transplant recipients. J Heart Lung Transplant. 2000;19:771–80.PubMedCrossRefGoogle Scholar
  131. 131.
    Bhorade SM, Sandesara C, Garrity ER, et al. Quantification of cytomegalovirus (CMV) viral load by the hybrid capture assay allows for early detection of CMV disease in lung transplant recipients. J Heart Lung Transplant. 2001;20:928–34.PubMedCrossRefGoogle Scholar
  132. 132.
    Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–7.PubMedCrossRefGoogle Scholar
  133. 133.
    Bewig B, Haacke TC, Tiroke A, et al. Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells. Respiration. 2000;67:166–72.PubMedCrossRefGoogle Scholar
  134. 134.
    Limaye AP, Raghu G, Koelle DM, et al. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy. J Infect Dis. 2002;185:20–7.PubMedCrossRefGoogle Scholar
  135. 135.
    Iwasenko JM, Scott GM, Naing Z, Glanville AR, Rawlinson WD. Diversity of antiviral-resistant human cytomegalovirus in heart and lung transplant recipients. Transpl Infect Dis. 2011;13:145–53.PubMedCrossRefGoogle Scholar
  136. 136.
    Husni RN, Gordon SM, Longworth DL, et al. Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients. Clin Infect Dis. 1998;26:753–5.PubMedCrossRefGoogle Scholar
  137. 137.
    Stern M, Hirsch H, Cusini A, et al. Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment. Transplantation. 2014;98:1013–8.PubMedCrossRefGoogle Scholar
  138. 138.
    Paraskeva M, Bailey M, Levvey BJ, et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans syndrome. Am J Transplant. 2011;11:2190–6.PubMedCrossRefGoogle Scholar
  139. 139.
    Palmer SM, Limaye AP, Banks M, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med. 2010;152:761–9.PubMedCrossRefGoogle Scholar
  140. 140.
    Jaksch P, Zweytick B, Kerschner H, et al. Cytomegalovirus prevention in high-risk lung transplant recipients: comparison of 3- vs 12-month valganciclovir therapy. J Heart Lung Transplant. 2009;28:670–5.PubMedCrossRefGoogle Scholar
  141. 141.
    Manuel O, Kumar D, Moussa G, et al. Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis. Transplantation. 2009;87:719–25.PubMedCrossRefGoogle Scholar
  142. 142.
    Vu DL, Bridevaux PO, Aubert JD, Soccal PM, Kaiser L. Respiratory viruses in lung transplant recipients: a critical review and pooled analysis of clinical studies. Am J Transplant. 2011;11:1071–8.PubMedCrossRefGoogle Scholar
  143. 143.
    Gottlieb J, Schulz TF, Welte T, et al. Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study. Transplantation. 2009;87:1530–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Bridevaux PO, Aubert JD, Soccal PM, et al. Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study. Thorax. 2014;69:32–8.PubMedCrossRefGoogle Scholar
  145. 145.
    Fuehner T, Dierich M, Duesberg C, et al. Single-centre experience with oral ribavirin in lung transplant recipients with paramyxovirus infections. Antivir Ther. 2011;16:733–40.PubMedCrossRefGoogle Scholar
  146. 146.
    McCurdy LH, Milstone A, Dummer S. Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin. J Heart Lung Transpl. 2003;22:745–53.CrossRefGoogle Scholar
  147. 147.
    Ng BJ, Glanville AR, Snell G, et al. The impact of pandemic influenza A H1N1 2009 on Australian lung transplant recipients. Am J Transplant. 2011;11:568–74.PubMedCrossRefGoogle Scholar
  148. 148.
    Soccal PM, Aubert JD, Bridevaux PO, et al. Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients. Clin Infect Dis. 2010;51:163–70.PubMedCrossRefGoogle Scholar
  149. 149.
    Kumar D, Husain S, Chen MH, et al. A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients. Transplantation. 2010;89:1028–33.PubMedCrossRefGoogle Scholar
  150. 150.
    Billings JL, Hertz MI, Wendt CH. Community respiratory virus infections following lung transplantation. Transpl Infect Dis. 2001;3:138–48.PubMedCrossRefGoogle Scholar
  151. 151.
    Garcia-Vidal C, Royo-Cebrecos C, Peghin M, et al. Environmental variables associated with an increased risk of invasive aspergillosis. Clin Microbiol Infect. 2014;20:O939–45.PubMedCrossRefGoogle Scholar
  152. 152.
    Wigle DA, Chaparro C, Humar A, et al. Epstein–Barr virus serology and posttransplant lymphoproliferative disease in lung transplantation. Transplantation. 2001;72:1783–6.PubMedCrossRefGoogle Scholar
  153. 153.
    Baldanti F, Rognoni V, Cascina A, Oggioni T, Tinelli C, Meloni F. Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients. Virol J. 2011;8:421.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Muchtar E, Kramer MR, Vidal L, et al. Posttransplantation lymphoproliferative disorder in lung transplant recipients: a 15-year single institution experience. Transplantation. 2013;96:657–63.PubMedCrossRefGoogle Scholar
  155. 155.
    Manuel O, Kumar D, Singer LG, et al. Incidence and clinical characteristics of herpes zoster after lung transplantation. J Heart Lung Transplant. 2008;27:11–6.PubMedCrossRefGoogle Scholar
  156. 156.
    Zuk DM, Humar A, Weinkauf JG, Lien DC, Nador RG, Kumar D. An international survey of cytomegalovirus management practices in lung transplantation. Transplantation. 2010;90:672–6.PubMedCrossRefGoogle Scholar
  157. 157.
    Lumbreras C, Manuel O, Len O, ten Berge IJM, Sgarabotto D, Hirsch HH. on behalf of the ESCMID Study Group of Infection in Compromised Hosts (ESGICH). Cytomegalovirus infection in solid organ transplant recipients. Clin Microbiol Infect. 2014;20 Suppl 7:19–26.PubMedCrossRefGoogle Scholar
  158. 158.
    Mitsani D, Nguyen MH, Kwak EJ, et al. Cytomegalovirus disease among donor-positive/recipient-negative lung transplant recipients in the era of valganciclovir prophylaxis. J Heart Lung Transplant. 2010;29:1014–20.PubMedCrossRefGoogle Scholar
  159. 159.
    Gross AE, Bryson ML. Oral ribavirin for the treatment of noninfluenza respiratory viral infections: a systematic review. Ann Pharmacother. 2015;49:1125–35.PubMedCrossRefGoogle Scholar
  160. 160.
    Burrows FS, Carlos LM, Benzimra M, et al. Oral ribavirin for respiratory syncytial virus infection after lung transplantation: efficacy and cost-efficiency. J Heart Lung Transplant. 2015;34:958–62.PubMedCrossRefGoogle Scholar
  161. 161.
    ter Meulen CG, Wetzels JF, Hilbrands LB. The influence of mycophenolate mofetil on the incidence and severity of primary cytomegalovirus infections and disease after renal transplantation. Nephrol Dial Transplant. 2000;15:711–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Infectious DiseasesHospital Universitari Vall d’HebronBarcelonaSpain
  2. 2.Department of PulmonologyHospital Universitari Vall d’HebronBarcelonaSpain

Personalised recommendations