Safety and efficacy of prophylaxis for Pneumocystis jirovecii pneumonia involving trimethoprim-sulfamethoxazole dose reduction in kidney transplantation

Abstract

Background Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti- Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear. Methods We performed a retrospective review of all patients transplanted between 2011 and 2015 prescribed daily single strength TMP-SMX for twelve months post-transplantation as PcP prophylaxis. Actual TMP-SMX dose and duration, adverse effects, number of dose reductions and reasons, and PcP events were captured. Multivariate logistic regression analyses for risk factors associated with dose reduction were performed. Results Of 438 KTR, 233 (53%) maintained daily TMP-SMX and 205 (47%) sustained ≥1 dose reduction, with the point prevalence of a reduced dose regimen being between 18 and 25%. 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. PcP 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 risked leukopenia (Odds Ratio 3.31, 95% CI 1.39–7.90, p = 0.006). Conclusions TMP-SMX dose reduction is frequent in the first post-transplant year but PcP does not occur. To limit the need for TMP-SMX dose reduction due to adverse effects, a clinical trial comparing daily to thrice weekly single strength TMP-SMX in de-novo KTR is justified.

Adverse effects of trimethoprim–sulfamethoxazole for the prophylaxis of Pneumocystis pneumonia in dermatology

“…Dermatologists frequently administrate TMP/SMX to patients with pemphigus, pemphigoid, dermatomyositis and systemic lupus erythematosus. Because we treat these patients with corticosteroids and/or immunosuppressants for a long period of time, adverse events often occur, so we often reduce the dose of TMP/SMX due to adverse events 3 . We have managed to use TMP/SMX without causing adverse events 4 .…”

“…Because we treat these patients with corticosteroids and/or immunosuppressants for a long period of time, adverse events often occur, so we often reduce the dose of TMP/SMX due to adverse events. 3 We have managed to use TMP/SMX without causing adverse events. 4 A non-blind randomized controlled trial is now in progress.…”

An open-label, randomized controlled trial of sulfamethoxazole–trimethoprim for Pneumocystis prophylaxis: results of 52-week follow-up

“…Prasad et al . [ 14 ] reported that SMX/TMP 400 mg/80 mg three times a week in renal transplant patients reduced AEs without affecting prophylaxis. Takenaka et al .…”

Lifelong, universal Pneumocystis jirovecii pneumonia prophylaxis: Patient uptake and adherence after kidney transplant

“…[11][12][13][14] Despite primary PJP prophylaxis, many studies report PJP cases and outbreaks occurring after prophylaxis, with an incidence of 44.6-176 cases per 100 000 person-years. 5,12,[14][15][16][17][18][19][20][21][22][23][24][25] Transmission of PJP occurs by two primary modes: contact with PJP-infected patients or asymptomatic carriers and environmental exposure. 18,20,21,23,24 This can result in spread amongst immunocompromised patients within a renal transplant centre leading to a PJP outbreak.…”

“…5,12,[14][15][16][17][18][19][20][21][22][23][24][25] Transmission of PJP occurs by two primary modes: contact with PJP-infected patients or asymptomatic carriers and environmental exposure. 18,20,21,23,24 This can result in spread amongst immunocompromised patients within a renal transplant centre leading to a PJP outbreak. 18,20,21,24 Universal prophylaxis has been used to manage such outbreaks, but evidence to guide the duration of prophylaxis is limited, leading to variability between transplant centres, ranging from 1 year after the last case to lifelong prophylaxis.…”