MON-189 SAFETY AND EFFICACY OF PROPHYLAXIS FOR PNEUMOCYSTIS JIROVECII PNEUMONIA INVOLVING TRIMETHOPRIM-SULFAMETHOXAZOLE DOSE REDUCTION IN KIDNEY TRANSPLANTATION

Abstract

Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti-Pneumocystis jirovecii pneumonia (PJP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PJP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PJP are unclear. The approach to using TMP-SMX is highly variable; in the first post-transplant year TMP-SMX dosing regimens range from one double-strength tablet daily to one single-strength tablet on alternate days. We performed a retrospective review of all patients transplanted at our institution between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PJP prophylaxis. Actual TMP-SMX dose and duration, adverse effects including hyperkalemia and leukopenia, number of dose reductions and the corresponding reasons, and PJP events were captured. Multivariate logistic regression analysis for risk factors associated with each reason for dose reduction was performed. Of 438 KTR transplanted during the pre-specified period, 233 KTR (53%) maintained daily TMP-SMX and 205 KTR (47%) sustained ≥ 1 dose reduction, with the point prevalence of a reduced dose regimen being between 18-25% over the course of the first post-transplant year. Median duration for daily TMP-SMX was 8.45/12 months, contributing 4137 patient-months daily TMP-SMX and 1110 patient-months with a reduced dose. PJP did not occur in any patients. There were 84 documented dose reductions for hyperkalemia and 102 for leukopenia, with 12 and 7 patients requiring TMP-SMX cessation. In multivariate analysis, a living donor transplant protected against hyperkalemia (Odds Ratio 0.46, 95% CI 0.26-0.83, p<0.01) while acute rejection was a risk factor for leukopenia (Odds Ratio 3.31, 95% CI 1.39-7.90, p=0.006). TMP-SMX dose reduction for adverse effect management is frequent in the first post-transplant year, but PJP fortunately does not occur as a result. Although an alternate-day single strength TMP-SMX dosing regimen seems reasonable, to limit the need for TMP-SMX dose reduction due to adverse effects a prospective clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.