Infections after Lung Transplantation

ABSTRACT

Despite advances in prophylaxis and therapy, infections remain a major source of morbidity and mortality after lung transplantation. Lung transplant recipients are at increased risk for both community-acquired and nosocomial pathogens, which may develop at various time points. The risk of infections increases with the intensity of immunosuppression. Careful assessment of the recipient is essential to assure adequate prophylactic or preemptive therapy. Aggressive prophylaxis for some infections (e.g., cytomegalovirus) has substantially reduced the prevalence of serious infections due to this organism. Tuberculin-positive individuals should be treated with prophylactic isoniazid to reduce the chance for reactivation of tuberculosis following transplantation. Myriad opportunistic pathogens (including various viruses, bacteria, fungi, etc.) may complicate transplantation, owing to the effects of multiagent immunosuppressive therapy. This review addresses the salient pathogens that may infect organ transplant recipients, and discusses strategies to prevent or treat specific pathogens in this highly susceptible patient population.

KEYWORDS

Infections - lung transplant - prophylaxis

REFERENCES

• 1 Fishman J A, Rubin R H. Infection in organ-transplant recipients.  N Engl J Med. 1998;  338 1741-1751
• 2 United Network of Organ Sharing .http://www.unos.org/PoliciesandBylaws2/policies/docs/policy_2.doc Accessed July 16, 2006
• 3 Screening of donor and recipient prior to solid organ transplantation.  Am J Transplant. 2004;  4(Suppl 10) 10-20
• 4 Hartwig M G, Patel V, Palmer S M et al.. Hepatitis B core antibody positive donors as a safe and effective therapeutic option to increase available organs for lung transplantation.  Transplantation. 2005;  80 320-325
• 5 Viral hepatitis guidelines in hemodialysis and transplantation.  Am J Transplant. 2004;  4(Suppl 10) 72-82
• 6 Shitrit A B, Kramer M R, Bakal I, Morali G, Ari Z B, Shitrit D. Lamivudine prophylaxis for hepatitis B virus infection after lung transplantation.  Ann Thorac Surg. 2006;  81 1851-1852
• 7 Mycobacterium tuberculosis.  Am J Transplant. 2004;  4(Suppl 10) 37-41
• 8 Dosanjh A, Theodore J, Pappagianis D. Probable false-positive coccidioidal serologic results in patients with cystic fibrosis.  Pediatr Transplant. 1998;  2 313-317
• 9 Guidelines for vaccination of solid organ transplant candidates and recipients.  Am J Transplant. 2004;  4(Suppl 10) 160-163
• 10 Hayney M S, Welter D L, Reynolds A M, Francois M, Love R B. High-dose hepatitis B vaccine in patients waiting for lung transplantation.  Pharmacotherapy. 2003;  23 555-560
• 11 Avlonitis V S, Krause A, Luzzi L et al.. Bacterial colonization of the donor lower airways is a predictor of poor outcome in lung transplantation.  Eur J Cardiothorac Surg. 2003;  24 601-607
• 12 Goldfarb N S, Avery R K, Goormastic M et al.. Hypogammaglobulinemia in lung transplant recipients.  Transplantation. 2001;  71 242-246
• 13 Maurer J R, Tullis D E, Grossman R F, Vellend H, Winton T L, Patterson G A. Infectious complications following isolated lung transplantation.  Chest. 1992;  101 1056-1059
• 14 Kanj S S, Tapson V, Davis R D, Madden J, Browning I. Infections in patients with cystic fibrosis following lung transplantation.  Chest. 1997;  112 924-930
• 15 Aris R M, Gilligan P H, Neuringer I P, Gott K K, Rea J, Yankaskas J R. The effects of panresistant bacteria in cystic fibrosis patients on lung transplant outcome.  Am J Respir Crit Care Med. 1997;  155 1699-1704
• 16 Nunley D R, Grgurich W, Iacono A T et al.. Allograft colonization and infections with Pseudomonas in cystic fibrosis lung transplant recipients.  Chest. 1998;  113 1235-1243
• 17 Bauldoff G S, Nunley D R, Manzetti J D, Dauber J H, Keenan R J. Use of aerosolized colistin sodium in cystic fibrosis patients awaiting lung transplantation.  Transplantation. 1997;  64 748-752
• 18 Balke B, Hogardt M, Schmoldt S, Hoy L, Weissbrodt H, Haussler S. Evaluation of the E test for the assessment of synergy of antibiotic combinations against multiresistant Pseudomonas aeruginosa isolates from cystic fibrosis patients.  Eur J Clin Microbiol Infect Dis. 2006;  25 25-30
• 19 Saiman L, Marshall B C, Mayer-Hamblett N et al.. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial.  JAMA. 2003;  290 1749-1756
• 20 Gerhardt S G, McDyer J F, Girgis R E, Conte J V, Yang S C, Orens J B. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study.  Am J Respir Crit Care Med. 2003;  168 121-125
• 21 Verleden G M, Vanaudenaerde B M, Dupont L J, Van Raemdonck D E. Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome.  Am J Respir Crit Care Med. 2006;  174 566-570
• 22 Nalca Y, Jansch L, Bredenbruch F, Geffers R, Buer J, Haussler S. Quorum-sensing antagonistic activities of azithromycin in Pseudomonas aeruginosa PAO1: a global approach.  Antimicrob Agents Chemother. 2006;  50 1680-1688
• 23 Snell G I, de Hoyos A, Krajden M, Winton T, Maurer J R. Pseudomonas cepacia in lung transplant recipients with cystic fibrosis.  Chest. 1993;  103 466-471
• 24 LiPuma J J. Burkholderia cepacia complex: a contraindication to lung transplantation in cystic fibrosis?.  Transpl Infect Dis. 2001;  3 149-160
• 25 De Soyza A, McDowell A, Archer L et al.. Burkholderia cepacia complex genomovars and pulmonary transplantation outcomes in patients with cystic fibrosis.  Lancet. 2001;  358 1780-1781
• 26 Aris R M, Routh J C, LiPuma J J, Heath D G, Gilligan P H. Lung transplantation for cystic fibrosis patients with Burkholderia cepacia complex: survival linked to genomovar type.  Am J Respir Crit Care Med. 2001;  164 2102-2106
• 27 Saiman L, Siegel J. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patient transmission.  Am J Infect Control. 2003;  31(Suppl 3) S1-62
• 28 Herridge M S, de Hoyos A L, Chaparro C, Winton T L, Kesten S, Maurer J R. Pleural complications in lung transplant recipients.  J Thorac Cardiovasc Surg. 1995;  110 22-26
• 29 Nunley D R, Grgurich W F, Keenan R J, Dauber J H. Empyema complicating successful lung transplantation.  Chest. 1999;  115 1312-1315
• 30 Steffenson D O, Dummer J S, Granick M S, Pasculle A W, Griffith B P, Cassell G H. Sternotomy infections with Mycoplasma hominis .  Ann Intern Med. 1987;  106 204-208
• 31 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 1131-1134
• 32 Hadjiliadis D, Howell D N, Davis R D et al.. Anastomotic infections in lung transplant recipients.  Ann Transplant. 2000;  5 13-19
• 33 Higgins R, McNeil K, Dennis C et al.. Airway stenoses after lung transplantation: management with expanding metal stents.  J Heart Lung Transplant. 1994;  13 774-778
• 34 Mughal M M, Gildea T R, Murthy S, Pettersson G, DeCamp M, Mehta A C. Short-term deployment of self-expanding metallic stents facilitates healing of bronchial dehiscence.  Am J Respir Crit Care Med. 2005;  172 768-771
• 35 Burns K E, Orons P D, Dauber J H et al.. Endobronchial metallic stent placement for airway complications after lung transplantation: longitudinal results.  Ann Thorac Surg. 2002;  74 1934-1941
• 36 Schenk P, Madl C, Kramer L et al.. Pneumatosis intestinalis with Clostridium difficile colitis as a cause of acute abdomen after lung transplantation.  Dig Dis Sci. 1998;  43 2455-2458
• 37 Nichols L, Strollo D C, Kusne S. Legionellosis in a lung transplant recipient obscured by cytomegalovirus infection and Clostridium difficile colitis.  Transpl Infect Dis. 2002;  4 41-45
• 38 Singh N, Stout J E, Yu V L. Prevention of Legionnaires' disease in transplant recipients: recommendations for a standardized approach.  Transpl Infect Dis. 2004;  6 58-62
• 39 Chow J W, Yu V L. Legionella: a major opportunistic pathogen in transplant recipients.  Semin Respir Infect. 1998;  13 132-139
• 40 de Bruyn G, Whelan T P, Mulligan M S, Raghu G, Limaye A P. Invasive pneumococcal infections in adult lung transplant recipients.  Am J Transplant. 2004;  4 1366-1371
• 41 Glanville A R, Gencay M, Tamm M et al.. Chlamydia pneumoniae infection after lung transplantation.  J Heart Lung Transplant. 2005;  24 131-136
• 42 Husain S, McCurry K, Dauber J, Singh N, Kusne S. Nocardia infection in lung transplant recipients.  J Heart Lung Transplant. 2002;  21 354-359
• 43 Janssens W, Van Raemdonck D, Dupont L, Verleden G M. Listeria pleuritis 1 week after lung transplantation.  J Heart Lung Transplant. 2006;  25 734-737
• 44 Fungal infections.  Am J Transplant. 2004;  4(Suppl 10) 110-134
• 45 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 1029-1033
• 46 Gordon S M, Avery R K. Aspergillosis in lung transplantation: incidence, risk factors, and prophylactic strategies.  Transpl Infect Dis. 2001;  3 161-167
• 47 Sole A, Morant P, Salavert M, Peman J, Morales P. Aspergillus infections in lung transplant recipients: risk factors and outcome.  Clin Microbiol Infect. 2005;  11 359-365
• 48 Singh N, Husain S. Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.  J Heart Lung Transplant. 2003;  22 258-266
• 49 Nunley D R, Gal A A, Vega J D, Perlino C, Smith P, Lawrence E C. Saprophytic fungal infections and complications involving the bronchial anastomosis following human lung transplantation.  Chest. 2002;  122 1185-1191
• 50 Palmer S M, Drew R H, Whitehouse J D et al.. Safety of aerosolized amphotericin B lipid complex in lung transplant recipients.  Transplantation. 2001;  72 545-548
• 51 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;  77 232-237
• 52 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;  4 195-200
• 53 Singh N. Antifungal prophylaxis in solid-organ transplant recipients: considerations for clinical trial design.  Clin Infect Dis. 2004;  39(Suppl 4) S200-S206
• 54 Wu G, Vilchez R A, Eidelman B, Fung J, Kormos R, Kusne S. Cryptococcal meningitis: an analysis among 5,521 consecutive organ transplant recipients.  Transpl Infect Dis. 2002;  4 183-188
• 55 Miller M B, Hendren R, Gilligan P H. Posttransplantation disseminated coccidioidomycosis acquired from donor lungs.  J Clin Microbiol. 2004;  42 2347-2349
• 56 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;  73 306-308
• 57 Husain S, Munoz P, Forrest G et al.. Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome.  Clin Infect Dis. 2005;  40 89-99
• 58 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;  37 221-229
• 58a 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;  28 240-246
• 59 Ettinger N A, Bailey T C, Trulock E P et al.. Cytomegalovirus infection and pneumonitis: impact after isolated lung transplantation. Washington University Lung Transplant Group.  Am Rev Respir Dis. 1993;  147 1017-1023
• 60 Cerrina J, Le Roy Ladurie F, Herve P H et al.. Role of CMV pneumonia in the development of obliterative bronchiolitis in heart-lung and double-lung transplant recipients.  Transpl Int. 1992;  5(Suppl 1) S242-S245
• 61 Soghikian M V, Valentine V G, Berry G J, Patel H R, Robbins R C, Theodore J. Impact of ganciclovir prophylaxis on heart-lung and lung transplant recipients.  J Heart Lung Transplant. 1996;  15 881-887
• 62 Kroshus T J, Kshettry V R, Savik K, John R, Hertz M I, Bolman III R M. Risk factors for the development of bronchiolitis obliterans syndrome after lung transplantation.  J Thorac Cardiovasc Surg. 1997;  114 195-202
• 63 Tamm M, Aboyoun C L, Chhajed P N, Rainer S, Malouf M A, Glanville A R. Treated cytomegalovirus pneumonia is not associated with bronchiolitis obliterans syndrome.  Am J Respir Crit Care Med. 2004;  170 1120-1123
• 64 Sharples L D, McNeil K, Stewart S, Wallwork J. Risk factors for bronchiolitis obliterans: a systematic review of recent publications.  J Heart Lung Transplant. 2002;  21 271-281
• 65 Neurohr C, Huppmann P, Leuchte H et al.. Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation: a risk factor for bronchiolitis obliterans syndrome?.  Am J Transplant. 2005;  5 2982-2991
• 66 Limaye A P, Raghu G, Koelle D M, Ferrenberg J, Huang M L, Boeckh M. High incidence of ganciclovir-resistant cytomegalovirus infection among lung transplant recipients receiving preemptive therapy.  J Infect Dis. 2002;  185 20-27
• 67 Hertz M I, Jordan C, Savik S K et al.. Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.  J Heart Lung Transplant. 1998;  17 913-920
• 68 Zamora M R, Nicolls M R, Hodges T N et al.. Following universal prophylaxis with intravenous ganciclovir and cytomegalovirus immune globulin, valganciclovir is safe and effective for prevention of CMV infection following lung transplantation.  Am J Transplant. 2004;  4 1635-1642
• 69 Zamora M R. Use of cytomegalovirus immune globulin and ganciclovir for the prevention of cytomegalovirus disease in lung transplantation.  Transpl Infect Dis. 2001;  3(Suppl 2) 49-56
• 70 Reams B D, McAdams H P, Howell D N, Steele M P, Davis R D, Palmer S M. Posttransplant lymphoproliferative disorder: incidence, presentation, and response to treatment in lung transplant recipients.  Chest. 2003;  124 1242-1249
• 71 Benden C, Aurora P, Burch M et al.. Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction.  J Heart Lung Transplant. 2005;  24 2103-2108
• 72 Community-acquired respiratory viruses.  Am J Transplant. 2004;  4(Suppl 10) 105-109
• 73 Adenovirus.  Am J Transplant. 2004;  4(Suppl 10) 101-104
• 74 Khalifah A P, Hachem R R, Chakinala M M et al.. Respiratory viral infections are a distinct risk for bronchiolitis obliterans syndrome and death.  Am J Respir Crit Care Med. 2004;  170 181-187
• 75 Billings J L, Hertz M I, Savik K, Wendt C H. Respiratory viruses and chronic rejection in lung transplant recipients.  J Heart Lung Transplant. 2002;  21 559-566
• 76 Hodges T N, Torres F P, Marqueson J, Diercks M, Zamora M R. Community acquired respiratory viruses in lung transplant patients: incidence and outcomes.  J Heart Lung Transplant. 2001;  20 169-170
• 77 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 2031-2036
• 78 Gerna G, Vitulo P, Rovida F et al.. Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients.  J Med Virol. 2006;  78 408-416
• 79 Ong J P, Barnes D S, Younossi Z M et al.. Outcome of de novo hepatitis C virus infection in heart transplant recipients.  Hepatology. 1999;  30 1293-1298
• 80 Cotler S J, Jensen D M, Kesten S. Hepatitis C virus infection and lung transplantation: a survey of practices.  J Heart Lung Transplant. 1999;  18 456-459
• 81 Kumar D, Prasad G V, Zaltzman J, Levy G A, Humar A. Community-acquired West Nile virus infection in solid-organ transplant recipients.  Transplantation. 2004;  77 399-402
• 82 Kumar D, Humar A. Emerging viral infections in transplant recipients.  Curr Opin Infect Dis. 2005;  18 337-341
• 83 Kumar D, Humar A. Pandemic influenza and its implications for transplantation.  Am J Transplant. 2006;  6 1512-1517