# Clinical outcomes after switching from sulfamethoxazole-trimethoprim to atovaquone due to intolerance in patients with non-HIV Pneumocystis pneumonia: a single-center retrospective study

## TL;DR

This study found that switching from sulfamethoxazole-trimethoprim to atovaquone in non-HIV Pneumocystis pneumonia patients due to intolerance does not worsen survival outcomes.

## Contribution

The study provides evidence on the safety and efficacy of atovaquone in non-HIV Pneumocystis pneumonia patients intolerant to sulfamethoxazole-trimethoprim.

## Key findings

- Switching to atovaquone was not associated with higher mortality compared to continuing sulfamethoxazole-trimethoprim.
- Over 30% of patients with non-HIV PCP were unable to tolerate sulfamethoxazole-trimethoprim therapy.
- The 30-day survival rate was similar between patients who switched to atovaquone and those who remained on sulfamethoxazole-trimethoprim.

## Abstract

Atovaquone (Atov), a second-line drug, is used to treat patients with Pneumocystis pneumonia (PCP) who cannot tolerate sulfamethoxazole/trimethoprim (SMX/TMP). However, the efficacy and safety of Atov are based on clinical trials conducted in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome, with limited data available on HIV-uninfected individuals with PCP (non-HIV PCP). In this study, we retrospectively evaluated the clinical outcomes of switching from SMX/TMP to Atov in patients with non-HIV PCP.

The study included patients with non-HIV PCP who were admitted to Fukuoka University Hospital between 2016 and 2023 and initially received SMX/TMP therapy. The primary endpoint was 30-day survival rate from the date of PCP diagnosis. Secondary endpoints included factors associated with mortality and the cumulative incidence of switching from SMX/TMP to Atov.

Of the 56 patients receiving SMX/TMP therapy for PCP, 17 were switched to Atov due to SMX/TMP-related side effects. The Kaplan–Meier estimated 30-day survival was 76.9% in the “remained on” SMX/TMP group and 82.4% in the “switched to” Atov group (log-rank test, P = 0.58). Univariable logistic regression analysis of 30-day mortality showed that switching to Atov was not associated with higher mortality compared with continued SMX/TMP therapy (odds ratio 0.71, 95% confidence interval 0.17 to 3.05). The Kaplan–Meier estimated cumulative incidence of switching from SMX/TMP to Atov during the PCP treatment period was 33.8%.

Our data suggest that switching from SMX/TMP to Atov may not be associated with worse survival. Long-term administration of SMX/TMP is often challenging due to its side effects, and in this study, more than 30% of patients were unable to tolerate its therapeutic dose. Our findings support the role of Atov as a viable second-line treatment for PCP in immunocompromised patients, such as those with non-HIV PCP.