The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies.
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.
Rubin
R H
RH
Massachusetts General Hospital, Boston, Massachusetts 02114-2686, USA. rhrubin@partners.org
Ikonen
T
T
Gummert
J F
JF
Morris
R E
RE
D000890:Anti-Infective Agents / Q000627:therapeutic use*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000276:immunology; D016377:Organ Transplantation; D014181:Transplantation Immunology
D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents