ORIGINAL RESEARCH|ARTICLES IN PRESS

Low- Versus Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Non-Human Immunodeficiency Virus-Infected Patients: A Multi-Center, Retrospective Observational Cohort Study

Tatsuya Nagai, Hiroki Matsui, Haruka Fujioka, et al

Chest Open AccessPublished:August 10, 2023

DOI:https://doi.org/10.1016/j.chest.2023.08.009

Abstract

Background

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without human immunodeficiency virus (HIV) infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited.

Research question

What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared to conventional-dose TMP-SMX after adjusting for patient background characteristics?

Study Design and Methods

In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low- (TMP <12.5 mg/kg/day) and conventional-dose groups (TMP 12.5–20 mg/kg/day). The primary endpoint was 30-day mortality, and the secondary endpoints were 180-day mortality, adverse events of grade 3 or greater per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores.

Results

Fifty-five patients in the low-dose and 81 in the conventional-dose groups were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of females was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/day in the low-dose group and 17.78 mg/kg/day in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs. 18.4%, P=0.080) or 180-day mortality (14.6% vs. 26.1%, P=0.141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs. 59.0%, P=0.005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P=0.158), respectively.

Interpretation

Survival was similar between the low- and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.