Opportunistic infections--coming to the limits of immunosuppression?

Abstract

Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients' recent and distant epidemiological exposures and all factors that contribute to the patient's net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future.

Figure 1.

The timeline of infections following organ transplantation. The risk for infection following organ transplantation follows a standard pattern with routine immunosuppression and infectious exposures. The potential pathogens for which the risk is modified by prophylaxis, including vaccinations and antimicrobial agents, are indicated (*). Individual risk is modified by events such as surgery, treatment of graft rejection, or malignancy. Note that graft rejection and drug reactions may be among noninfectious causes of fever in transplant recipients. (From Fishman 2007; modified, with permission, from the author.)

Figure 2.

The impact of infectious exposures, inflammation, the microbiome, heterologous immunity, and innate immune stimulation on transplantation. The microbiome is the sum of colonizing organisms, acute and chronic infections, and reflects alterations in this flora by the immune system, vaccination, or antimicrobial agents. Antigens and activating molecular patterns from microbes or damaged tissues are released during all phases of transplantation and are present during graft rejection, immunosuppression, and/or immune reconstitution following lymphocyte depletion. These antigenic exposures and inflammatory mediators shape immune function via both the innate and adaptive immune systems and impact the outcome of transplantation (see also Chong and Alegre 2012).