# Risk factors for adverse events associated with trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia in non-human immunodeficiency virus-infected patients: a multicenter, retrospective, observational cohort study

## TL;DR

This study identifies risk factors for severe side effects of a common treatment for a type of pneumonia in non-HIV patients.

## Contribution

The study identifies pretreatment serum sodium, potassium levels, and initial drug dose as novel risk factors for adverse events in non-HIV PCP patients treated with SXT.

## Key findings

- Serum sodium, potassium levels, and initial trimethoprim dose per weight are independent risk factors for severe adverse events.
- Skin rashes, hyponatremia, and hyperkalemia were the most frequent adverse events in treatment failure cases.
- Baseline characteristics like electrolyte levels and drug dosing significantly differ between patients with and without adverse events.

## Abstract

Pneumocystis jirovecii pneumonia (PCP) is a severe opportunistic infection. Trimethoprim-sulfamethoxazole (SXT) is the first-choice treatment for PCP in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. However, the high incidence of adverse events makes treatment with SXT difficult. The risk factors for these adverse events in patients with non-HIV PCP remain unclear.

In this multicenter, retrospective, observational cohort study, we investigated these risk factors by analyzing data from patients with non-HIV PCP treated with SXT between June 2006 and March 2021 across three institutions. Patients were divided into two groups based on the presence of grade 3 or higher adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: the adverse event (n = 74) and no adverse event (n = 62) groups. Patient characteristics were compared, and multivariate regression analysis was used to identify factors contributing to adverse events. We also investigated the relationship between treatment failure and adverse events.

Baseline characteristics showed notable variations between the groups, notably in serum sodium, serum potassium levels, and the initial trimethoprim dose per weight. Logistic regression analysis revealed significant associations among adverse events and these three baseline variables. In the treatment failure group, the most frequent adverse events included skin rashes, hyponatremia, and hyperkalemia.

Pretreatment serum sodium and potassium levels and the initial SXT dose per weight were identified as independent risk factors for developing CTCAE grade 3 or higher adverse events associated with SXT treatment for non-HIV PCP. Further large-scale, prospective studies are essential to confirm these results.

The online version contains supplementary material available at 10.1186/s12879-026-12600-7.