Bacterial, mycobacterial, and protozoal infections after liver transplantation—Part I

Infection is one of the leading causes of morbidity and mortality in liver transplant recipients. More than two-thirds of liver transplant recipients have infection in the first year after transplantation, and infection is the leading cause of death in these patients.1 In addition, release of cytokines during the infection may have other indirect and negative effects, including allograft injury, opportunistic superinfection, and malignancy.1 The risk of infection in liver transplant recipients is determined by the intensity of exposure to infectious agents (hospital or community sources) and the overall immunosuppression level. This “net state of immunosuppression”2 is influenced by the dose, duration, sequence, and choice of immunosuppressive medications, underlying immune deficiencies, the presence of neutropenia or lymphopenia, mucocutaneous barrier integrity, the presence of necrotic tissue, ischemia or fluid collection, metabolic conditions such as diabetes mellitus, and the activity of immunomodulating viruses.2 After solid organ transplantation, there are 3 time periods when specific infections are likely to occur. The patient’s susceptibility to infection during these periods is strongly influenced by surgical factors, the level of immunosuppression and environmental exposure, and the dose, duration, and types of prophylaxis.3,4 Figure 1 depicts an infection time line of typical organisms after solid organ transplantation. During the first period, the month immediately after transplantation, most infections are related to technical or surgical issues and complications. Exposure to infectious agents through prolonged hospitalization before transplantation or during postoperative care may also result in infection. Bacterial and candidal wound infections, urinary infections, catheter-related infections, pneumonias, and Clostridium difficile colitis predominate during this period, and the etiologic organisms are similar to hospital-acquired infections common in other surgical patients.4,5 Although its incidence has markedly diminished with prophylaxis, reactivated human herpesvirus 1 (herpes simplex virus) is also a common viral illness in this time frame. The next period encompasses the second through sixth posttransplant months. During this time, infections from opportunistic organisms predominate as a result of cumulative immunosuppression. Typical infectious organisms of this period include cytomegalovirus, Pneumocystis jiroveci, and Aspergillus species. Other viruses (human herpesvirus 6, hepatitis B and C, human herpesvirus 3 [varicella-zoster virus], and others), fungi (Cryptococcus, Histoplasma, and Coccidioides species), and bacteria (Nocardia species, Listeria species, or Mycobacterium tuberculosis) may also be seen.4 From approximately the seventh to 12th posttransplant months and beyond, most recipients acquire infections such as influenza, urinary tract infections, and community-acquired pneumonias, which are similar to the infections acquired by patients who have not received transplants.4,6,7 Reactivation of human herpesvirus 3 may manifest as herpes zoster, and although it is uncommon, cytomegalovirus infections can occur. Three notable scenarios may enhance patient susceptibility to opportunistic infections, including (1) acute organ rejection necessitating increased immunosuppression therapy, (2) retransplantation, which “restarts” the immunosuppression and infection time line, and (3) chronic viral infections such as human immunodeficiency virus or hepatitis B or C.4 Kusne et al.8 studied 101 consecutive liver transplantation patients for 1 year or longer. The patients received antibiotics for wound prophylaxis for 5 days and nystatin for antifungal prophylaxis for 30 days. No prophylaxis was administered for pneumocystic or viral infections. Figure 2 shows the timing of all severe infections and separately profiles the rates of bacterial, fungal, viral, and protozoal infections. The majority of infections occurred within 6 months of transplantation. Abbreviations: OLT, orthotopic liver transplantation; VRE, vancomycin-resistant enterococci. From the Division of Infectious Diseases, Mayo Clinic, Scottsdale, AZ. Received September 7, 2005; accepted September 13, 2005. Address reprint requests to: Janis E. Blair, MD, Division of Infectious Diseases, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259. Copyright © 2005 by the American Association for the Study of Liver Diseases Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/lt.20624