Increased infections associated with the use of OKT3 for treatment of steroid-resistant rejection in renal transplantation.
We compared the infections encountered in 23 renal transplant patients given the monoclonal anti-T-cell antibody, Orthoclone OKT3 (OKT3), for treatment of steroid-resistant rejection in 1986 and in 23 control patients from 1984 to 1985 with resistant rejection matched demographically, for severity of rejection and for risk factors predisposing to infection, who did not receive OKT3; recipients of OKT3 received substantially less prednisone, cyclosporine, and antilymphocyte globulin (ALG) than control patients for treatment of the rejection episode. Fourteen (61%) patients given OKT3 developed one or more infections in the 3-month period following treatment as compared with 9 control patients (39%) given conventional antirejection therapy with high-dose steroids and, usually, ALG. Patients given OKT3 were significantly more likely to develop serious infections (pneumonia, bacteremia, meningitis, or severe viral infection; 16 episodes vs. 4, P = .02). Six recipients of OKT3 (26%) acquired infections typically encountered in states associated with depressed cell-mediated immunity (CMI)--Listeria sepsis (2), disseminated nocardiosis and Mycobacterium tuberculosis infection (1), cytomegalovirus (CMV) pneumonia (1), Yersinia infection with severe dermatophytosis (1), and Epstein-Barr virus-associated lymphoproliferative syndrome (1)--as compared with 1 case of mild CMV infection in the control group (P = .08). Trimethoprim-sulfamethoxazole (TMP-SMZ) was given to 19 patients in each group; all 4 recipients of OKT3 who did not receive TMP-SMZ prophylaxis developed life-threatening infection, 3, bacteremia (2 with Listeria) and 1, disseminated nocardiosis and M tuberculosis infection. These data suggest that OKT3 given for treatment of resistant rejection in renal transplantation predisposes the patient to serious infection, particularly with opportunistic pathogens characteristically associated with depressed cell-mediated immunity. Prophylaxis with TMP-SMZ, which is safe, well tolerated, and effective for reducing the incidence of infection in renal transplantation, may be especially important during OKT3 therapy.
Oh
C S
CS
Department of Surgery, University of Wisconsin Medical School, Madison 53792.
Stratta
R J
RJ
Fox
B C
BC
Sollinger
H W
HW
Belzer
F O
FO
Maki
D G
DG
D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D004351:Drug Resistance; D006084:Graft Rejection; D006801:Humans; D007239:Infections / Q000209:etiology*; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion / Q000009:adverse effects*; D011183:Postoperative Complications / Q000209:etiology*; D011241:Prednisone / Q000008:administration & dosage
D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D003524:Cyclosporins; D001379:Azathioprine; D011241:Prednisone