Rates of Trimethoprim-Sulfamethoxazole Versus Alternative Pneumocystis Prophylaxis Agents in Patients Undergoing Hematopoietic Stem Cell Transplantation

BACKGROUND

Pneumocystis jirovecii pneumonia (PJP) is an established opportunistic infection following hematopoietic stem cell transplant (HSCT). While trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis (ppx) is preferred for its efficacy and coverage, a variety of adverse events may lead to discontinuation, ranging from laboratory abnormalities to symptomatic adverse effects. The objective of this study was to evaluate PJP prophylactic prescribing practices, rates of adverse events, and rates of TMP-SMX discontinuation in the first 100 days post-HSCT.

METHODS

We performed a single-center, retrospective cohort study of 265 patients undergoing autologous or allogeneic HSCT from January 1st, 2010 - December 31st, 2012 (early cohort) and January 1st, 2020 - December 31st, 2022 (late cohort). This was performed in order to compare outcomes across two populations. The primary outcome of interest was the rate of first-line PJP prophylaxis with TMP-SMX. Secondary outcomes included alternate PJP prophylaxis, duration of TMP-SMX use, reasons for TMP-SMX discontinuation, and infections within the first 100 days post-HSCT. Descriptive statistics were employed, and comparison between cohorts was performed using student t-test, fisher exact testing, and chi-square analysis.

RESULTS

We included 265 patients (116 early vs. 149 late). The median age was 57 years (IQR 46-64). The most common indications for HSCT were multiple myeloma (27%), acute myeloid leukemia (24%), and non-Hodgkin lymphoma (18%). PJP ppx with TMP-SMX was used in 168 subjects (65.4%). Atovaquone was the most prescribed alternative agent (n=114; 66%). There were no differences in prescribing patterns of primary PJP ppx with TMP-SMX between early and late cohorts (p=0.50), however, there were significant differences in use of alternative PJP ppx with higher rates of pentamidine use in the early cohort (p< 0.001). TMP-SMX was discontinued in 48% of patients during the first 100 days; reasons included cytopenia (44%), kidney injury (21%), rash (17%), transaminase elevation (8%), pruritus (3%), or allergy (3%). TMP-SMX discontinuation was higher in the early vs. the late cohort (p < 0.001). In addition, 32 of 116 patients in the early cohort had documented infections within the first 100 days, while 30 of 149 patients in the late cohort had documented infections. The most common organisms identified were Clostridioides Difficile, Cytomegalovirus, Human Herpesvirus 6, and Coagulase Negative Staphylococci.

CONCLUSIONS

In this single-center retrospective cohort study, TMP-SMX was the most commonly prescribed agent for PJP prevention after HSCT. Early discontinuation of TMP-SMX was frequent and noted in nearly half of patients, with cytopenia being the most cited reason for discontinuation along with rash and kidney injury noted as other common reasons. However we identified significantly decreased rates of discontinuation of TMP-SMX among the late cohort as compared the early cohort. Use of second- and third-line agents for PJP prophylaxis may provide gaps in antimicrobial coverage. Further data are needed as to whether TMP-SMX may be safely reintroduced in patients who have had the drug discontinued for non-allergy indications, in order to provide optimal PJP prophylaxis for patients who have undergone HSCT.

Alonso:Cidara Therapeutics: Consultancy; DSM-Firmenich: Consultancy; American Society of Health System Pharmacists and Clinical care options: Honoraria; Pfizer: Consultancy; Merck: Consultancy, Research Funding; AiCuris: Consultancy; Academy for Continued Healthcare Learning: Honoraria.