Portal de Periódicos da CAPES

INFECTIOUS COMPLICATIONS OF SOLID ORGAN TRANSPLANTATIONS

2001; Elsevier BV; Volume: 15; Issue: 2 Linguagem: Inglês

10.1016/s0891-5520(05)70158-6

1557-9824

David M. Simon, Stuart Levin,

Parvovirus B19 Infection Studies

Solid organ transplantation (SOT) has emerged as a lifesaving therapy for many patients with end organ failure. Allograft and patient survival rates continue to improve. For example, less than 40% of liver transplant recipients survived to one year before 1980, compared to greater than an 80% survival rate today.16 The major factor in improved clinical outcome is the dramatic decline in death secondary to infection. Before 1980, nearly two-thirds of kidney and liver transplant recipients developed at least one infectious complication in the first year post-transplant that was associated with a mortality rate approaching 50%. Currently, 1-year mortality caused by infection has decreased to less than 5% for renal transplant patients and is down to 10% in liver allograft recipients.16, 22 Advances in surgical techniques, organ preservation, and improved postoperative care have contributed to more favorable outcome in these patients. Other factors that have positively impacted infection rates in these patients include pretransplant evaluation by infectious disease experts, vaccination, primary antibiotic prophylaxis, improved diagnostics, pre-emptive antibiotic therapy in high risk patients, and effective infection control practices. More selective immunosuppressive agents and more attention to prevention of cytomegalovirus (CMV) infection have been among the most significant changes. Despite these advancements, infection remains a serious life-threatening complication of solid organ transplantation. The risk of infection is directly related to the functional status of the immune system. A complex interplay of factors determines the net state of immunosuppression in solid organ transplant recipients.18 These factors include the presence of underlying diseases, postoperative metabolic factors, and concurrent infection with immunomodulatory viruses such as CMV, Ebstein-Barr virus (EBV), and HIV. More importantly, the type, dose, and duration of immunosuppressive therapy required to prevent and treat allograft rejection is the critical determinant of immune competence in SOT patients. The immunosuppressive drugs currently available are summarized in Table 1. In general, these agents prevent the initiation and coordination of allograft rejection by CD4 T lymphocytes. Other effects of these drugs include leukopenia and inhibition of antibody production. The use of cyclosporine (CsA)-based regimens has led to a decline in the number of rejection episodes, decreasing the requirement for corticosteroids and antilymphocyte globulin (ALG). This decrease in overall immunosuppression has been followed by a decrease in the number of life-threatening opportunistic infections.34 The incidence of infection is determined by the interaction between epidemiologic exposures and net state of immunosuppression. These epidemiologic exposures include community exposures to endemic mycoses, mycobacteria, strongyloides, and viruses such as influenza. Nosocomial exposures to aspergillus and legionella have led to outbreaks. The donor organ has been identified as a source for transmitting various infectious agents (Table 2).26 Transfusion-related infection has been dramatically reduced by prescreening blood products or by using leukocyte filtering techniques to decrease the risk of CMV transmission from unscreened blood products. Post-transplantation, the presence of central lines, urinary catheters, open wounds, and endotracheal intubation provide portals of entry for bacterial and fungal organisms. The type of infection in SOT patients follows certain predictable patterns based on the time following transplantation and conveniently are divided into three periods.18 An aggressive approach to determine the causative agent is mandatory for optimal selection of anti-infective agents and the need for surgical intervention. Infections in the early period (the first month after transplant) are similar to infections that occur in immunocompetent postoperative patients. Infections caused by endogenous flora from the gastrointestinal tract, including Candida, and hospital acquired bacteria are common. Typically the specific site of transplantation and allograft are the most likely site of infection. Tissue ischemia contributes to infection risk. For example, liver transplant recipients are at risk for biliary sepsis and liver abscess. Heart transplant patients are at risk for mediastinitis, mycotic aneurysm at the aortic suture line, and pneumonia. The bronchial anastomosis in the lung transplant can be disrupted by infection. The only significant viral infection observed during the early period after transplant is caused by recurrent herpes simplex virus (HSV). The incidence of HSV infection has been reduced by prophylactic antiviral therapy. The middle period from the beginning of the second month until 6 months post-transplantation is the period of maximum T-cell immune dysfunction. Infectious agents typically associated with this period often can be categorized as intracellular pathogens, and include CMV, human herpes virus-6 (HHV-6), Pneumocystis carinii (PC), Listeria monocytogenes, Cryptococcus neoformans, and Toxoplasma gondii. Reactivation syndromes caused by Mycobacterium tuberculosis, and endemic mycoses such as histoplasmosis and coccidiomycosis emerge generally during this period. Infections that occur during the third period beyond 6 months post-transplant are dependent on the net state of immunosuppression of the patient. Patients suffering from recurrent episodes of rejection and requiring excessive doses of immunosuppressive agents remain at risk for infection caused by PC, cryptococci, aspergillis, and others. Patients who require less immunosuppressive therapy still remain at risk for community-acquired infection caused by pneumococci and influenza. In addition, cryptococcal disease and CMV retinitis may occur in this period despite minimum immunosuppression.