Risk factors for adverse events of trimethoprim-sulfamethoxazole treatment in patients with non-HIV-PCP: a multi-centre, retrospective observational cohort study

<bold>Introduction:</bold> Pneumocystis pneumonia in nonhuman immunodeficiency virus (non-HIV-PCP) is a severe respiratory disease with a high mortality rate. Trimethoprim-sulfamethoxazole (TMP-SMX) treatment is the first-line treatment for PCP, but it is associated with a high frequency of adverse events (AEs). While previous studies have evaluated the risk factors for AEs of TMP-SMX administration in the treatment of HIV-PCP, studies assessing these risk factors for adverse reactions in non-HIV-PCP cases remain limited. <bold>Objective:</bold> This study aims to identify risk factors for the occurrence of AEs in TMP-SMX treatment specifically in patients with non-HIV-PCP. <bold>Methods:</bold> Patients diagnosed with non-HIV-PCP and treated with TMP-SMX at three tertiary care hospitals in Japan between June 2006 and March 2021 were included. AEs of grade ≥3 were evaluated using common terminology criteria for adverse events v5.0. Adjusted odds ratios (aOR) for adverse drug events were calculated using logistic regression analysis. <bold>Results:</bold> A total of 136 patients (mean age; 70.7 years, 55.1% women) were included in the study. Sixtyt-two of 136 patients (45.6%) had grade ≥3 AEs. In multivariate analysis, significant risk factors were the initial dose of TMP-SMX per body weight (TMP equivalent mg/kg/day, aOR; 1.176, 95%CI; 1.063–1.309), serum sodium level (mEq/L, aOR; 0.884, 95%CI; 0.793–0.978), and serum potassium level (mEq/L, aOR; 2.646, 95%CI; 1.174–6.418). <bold>Conclusions:</bold> In this study, TMP-SMX initial dose, hyponatremia, and hyperkalaemia were indepedent risk factors for AEs of TMP-SMX administraion in the treatment of non-HIV-PCP.