Tolerability of Low-Dose Sulfamethoxazole/Trimethoprim for Pneumocystis Jirovecii Pneumonia Prophylaxis in Kidney Transplant Recipients

Abstract

Background- Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection seen in immunosuppressed patients, including solid-organ transplant recipients. Sulfamethoxazole/trimethoprim (SMX/TMP) has long been considered first-line therapy for PCP prophylaxis. Optimal dosing regimens in solid-organ transplant recipients have not been fully defined. Objective-To examine the tolerability of a 1-year, 3-times weekly, prophylactic regimen of a single-strength SMX/TMP tablet. Study Design-Single-center, retrospective cohort study. Setting-A tertiary-care medical center, including inpatient hospitalizations and outpatient transplant clinic visits. Patients-Adult patients who received a kidney transplant between December 1, 2010, and November 30, 2012, at Hartford Hospital. Patients receiving a concurrent extrarenal transplant were excluded. Patients' charts were reviewed for up to 1 year after transplant. Results-A total of 88 patients were included in the analysis. Sixty-seven patients finished a full year of SMX/TMP after transplant, 10 patients discontinued SMX/TMP less than 1 year after transplant, and 11 patients started taking atovaquone instead of SMX/TMP after transplant. Documented reasons for discontinuation included hyperkalemia, leukopenia, diarrhea, and simplification of medication regimen. Patients without a documented reason for discontinuation did not have any obvious anomalies in laboratory values that would account for the discontinuation. Patients who received atovaquone for PCP prophylaxis had higher rates of recurrent urinary tract infections than did patients who received SMX/TMP for prophylaxis (33% vs 7%, P = .02). A longer postoperative stay (median [interquartile range, IQR] 13 [8.25-26] days vs 7 [6-9.5] days, P = .02), higher rates of delayed graft function (50% vs 10%, P = .004), as well as higher serum creatinine levels on postoperative day 7 (6.25 [2.4-10.1] mg/dL vs 1.8 [1.2-4.2] mg/dL, P= .01), postoperative month 1 (1.9 [0.8] mg/dL vs 1.4 [0.5] mg/dL, P = .002), and postoperative month 12 (1.6 [0.5] mg/dL vs 1.3 [0.3] mg/dL, P = .04) were associated with early SMX/TMP discontinuation. Conclusion-A low-dose prophylactic SMX/TMP regimen of 1 single-strength tablet 3 times weekly is well tolerated. Discontinuation rates were lower than other rates reported for higher-dose regimens.

Higher risk of urinary tract infections in renal transplant recipients receiving pentamidine versus trimethoprim‐sulfamethoxazole (TMP‐SMX) for Pneumocystis pneumonia prophylaxis

“…However, this suggestion is noted to be based on evidence of moderate quality 32 . Reported rates of TMP‐SMX intolerance in renal transplant recipients due to drug‐related adverse effects range from 2.6% to 38% 18,19,22,33 . These patients require PCP prophylaxis with alternate agents such as atovaquone, dapsone, or aerosolized pentamidine which lack coverage against other common infections including UTI.…”

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients

“…The avoidance of TMP‐SMX for reasons of myelosuppression also appears unfounded, as rates of leukopenia in solid organ transplant cohorts when TMP‐SMX is employed as prophylaxis have been reported at less than 2% . Modern studies have suggested that TMP‐SMX therapy when employed as prophylaxis in hematological malignancy does not impact on the degree or duration of neutropenia .…”

“…13 We observed suboptimal G6PD screening in our dapsone patient cohort, with less than half under- The avoidance of TMP-SMX for reasons of myelosuppression also appears unfounded, as rates of leukopenia in solid organ transplant cohorts when TMP-SMX is employed as prophylaxis have been reported at less than 2%. 16,17 Modern studies have suggested that TMP-SMX therapy when employed as prophylaxis in hematological malignancy does not impact on the degree or duration of neutropenia. 18 A recent Cochrane review of PJP prophylaxis in the non-HIV setting found no difference in adverse events requiring discontinuation when comparing TMP-SMX to no treatment or placebo.…”

Electrolyte and Acid-Base Disorders in the Renal Transplant Recipient

“…Medications used post-transplant are thought to be the major cause for post-transplant hyperkalemia in recipients with a well-functioning graft. Use of trimethoprim in Trimethoprim/Sulfamethoxazole (TMP/SMX) in standard doses contributes to hyperkalemia by ENaC blockade ( 7 ) but the incidence is low especially when the regimen comprises of single strength tablet three times weekly for Pneumocystis and urinary tract infection prophylaxis ( 8 ). Use of pentamidine can also cause hyperkalemia by a similar mechanism ( 9 ).…”