311 - Risk Factors and Approaches to Infections in Transplant Recipients

Abstract

Successful clinical organ transplantation dates from 1954, when the immunologic barrier to transplantation was ingeniously circumvented in a few patients with kidney failure by using organs from donors who were identical twins with the patients. Subsequently, transplantation of organs from genetically different individuals was attempted with lymphoid irradiation to suppress the recipient’s immune response to the allograft, but these efforts met with only occasional success. In the early 1960s, immunosuppressive regimens employing azathioprine and corticosteroids were introduced. These provided more effective control of allograft rejection that not only was sustainable but could be adjusted according to an individual patient’s circumstances. This development catapulted kidney transplantation beyond the experimental stage, and both living-related and cadaveric renal transplantation became part of regular clinical practice. Attempts at heart and liver transplantation proved more challenging, and these clinical efforts remained limited to a few dedicated programs for more than a decade. The next major watershed in the development of transplantation was the introduction of cyclosporine in the early 1980s. This development ushered in a marked expansion of heart and liver transplantation, promoted further growth of renal transplantation, and made lung transplantation possible. Currently, more than 28,000 solid organ transplantations are performed yearly in the United States, and most patients retain the grafts and survive many years after transplantation. As a result, patients with various types of transplants are now routinely encountered in general practice. Except for issues related to the function and rejection of the transplanted organ, infections are the most important problem after transplantation. The clinical manifestations of infection are variable and depend on the infecting pathogen, the prior immune status of the host, the type of transplantation, the time after transplantation, and the level of pharmacologic immunosuppression. With this complexity in mind, it is useful to address some general principles that may aid in the diagnosis, management, and understanding of infections after transplantation. The occurrence of infection requires a susceptible host and an available pathogen. Transplant recipients are not equally susceptible to all pathogens. For instance, most enteroviruses do not appear to infect transplant recipients with greater frequency or severity than they do normal hosts. A transplant recipient also may be quite susceptible to a given pathogen but may have a low risk of infection because of lack of exposure. For example, tuberculosis is rarely encountered at most transplantation centers in developed countries, but it can be a major problem in transplant recipients in parts of the world and in clinical settings in which infection cannot be avoided. Likewise, transplant recipients with no past exposure to cytomegalovirus (CMV) who receive organs from CMV-seronegative donors are at low risk for CMV infection, whatever their level of immunosuppression. In clinical practice, the clinician can and should use this sort of information to assess each patient’s individual susceptibility to important pathogens. Infections are most frequent and most varied during the first 6 months after transplantation. During this period, patients have all the risk factors for infection (Table 310-1): They may still be affected— either directly or indirectly—by their underlying disease; because they have undergone major surgery and been in the intensive care unit, they are at risk for wound and other nosocomial infections; and because they have received large doses of immunosuppressive drugs, the allograft may be malfunctioning as a result of rejection or other factors. This early period also covers the time of highest risk for infection by opportunistic microorganisms such as CMV and Nocardia, Aspergillus, Pneumocystis, or Toxoplasma organisms. These pathogens received much attention in the early literature on transplantation-related infections; more recently, their clinical impact has been diminished by the widespread use of antimicrobial prophylactic regimens early after transplantation. These regimens have virtually eliminated some infectious complications, such as Pneumocystis pneumonia, and have provided substantial but still imperfect control of others, such as CMV disease. With time—usually about 6 to 9 months after transplantation—the risk of infection tends to decrease. The level of vigilance may therefore be reduced, except for individual patients whose risk has remained high because of continued requirement for high doses of immunosuppression.