The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies

Abstract

Infection and rejection, the two major barriers to successful organ transplantation, are closely linked, with immunosuppressive therapy being central to the pathogenesis of both. After almost two decades when azathioprine and prednisone, supplemented by antilymphocyte antibody therapy, were the cornerstones of post-transplant immunosuppressive programs, there has been a major increase in the therapeutic armamentarium available to treat rejection: cyclosporine, tacrolimus, mycophenolate mofetil, rapamycin, and antibodies directed against the interleukin-2 receptor. These agents are potent inhibitors of microbial specific T cell function, thus potentiating opportunistic infection with herpes group viruses, fungal and mycobacterial species, Strongyloides stercoralis, and a variety of intracellular pathogens. The mechanisms by which each of these drugs exerts its effects are an important determinant of the antimicrobial strategies that will be necessary to combat infection. Indeed, strategies to limit these infections are being linked to the nature of the immunosuppressive therapy required in a particular patient. Thus, the therapeutic prescription for the transplant patient is said to have two components: an immunosuppressive component to prevent and treat rejection, and an antimicrobial one to make it safe. In addition to using antimicrobial agents therapeutically, in the transplant patient prevention is stressed in which antibiotics are deployed prophylactically or preemptively.

Delivery of rapamycin to dendritic cells using degradable microparticles

“…Long-term systemic administration of immunosuppressive drugs is associated with numerous side effects including, but not limited to, increased risk of cardiovascular diseases, and enhanced risk of malignancies and opportunistic infections[5, 6]. There have also been numerous reports describing their hepatic and renal toxicities[7, 8].…”

Infections and anti–tumor necrosis factor α therapy

“…In the absence of any established controlled clinical trials designed to investigate strategies to limit anti-TNF␣-associated infections, it is necessary to propose guidelines based on case reports, case series, anecdotal experience, and expert opinion. For other groups of immunocompromised patients, the concept of the therapeutic prescription (3) has been advocated, and it has been shown to be effective in the arena of transplantation. The therapeutic prescription has 2 components: an immunomodulating effect to control the underlying condition and an antimicrobial program to make disease-modifying therapy safer.…”

Development of a Rapid Serological Assay for the Diagnosis of Strongyloidiasis Using a Novel Diffraction-Based Biosensor Technology

“…With increasing use of corticosteroids and other immunosuppressive/immunomodulatory therapies for the treatment of a wide variety of disease states [12], [34]–[36], there is considerable cumulative life-time risk of release of S. stercoralis from immune control. Disseminated disease in these individuals can be associated with high mortality [12], [37]–[40].…”