Are Lower Trimethoprim–Sulfamethoxazole Doses Effective for Pneumocystis Pneumonia?

Thomas Glück, MD reviewing Creemers-Schild D et al. Infection 2015 Oct 15.

Half of the currently recommended dose may be sufficient, and patients who improve rapidly can be switched to a low dose.

Current guidelines recommend treating Pneumocystis jirovecii pneumonia (PCP) with high-dose trimethoprim–sulfamethoxazole (TMP–SMX; TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day in 4 divided doses) for 2 to 3 weeks. Given the high frequency of adverse events associated with this regimen — including renal insufficiency, electrolyte disorders, and liver toxicity — researchers in the Netherlands retrospectively examined the efficacy of a TMP–SMX dose step-down strategy in 104 patients with confirmed PCP.

All patients received TMP–SMX doses lower than previously recommended. Eighty patients (77%) received standard therapy with intermediate-dose TMP–SMX (TMP 10–15 mg/kg/day and SMX 50–75 mg/kg/day) for ≥2 weeks; most patients (91%) were treated for 2 weeks and 9% for ≥3 weeks. Twenty-four patients (23%) were switched to low-dose TMP–SMX (TMP 4–6 mg/kg/day and SMX 20–30 mg/kg/day) after a median of 4.5 days (interquartile range, 2.8–7.0 days), either because of a favorable course, TMP–SMX toxicity, or both. The step-down and intermediate-dose groups did not vary significantly in prevalences of underlying conditions (HIV infection, 21% and 15%, respectively; solid organ transplantation, 25% and 34%; hematologic malignancy, 29% and 31%).

All-cause mortality tended to be lower in the step-down group than in the intermediate-dose group (30-day mortality, 4% and 16%; P=0.13; 100-day mortality, 8% and 25%; P=0.08). The median length of hospitalization was similar between groups (approximately 15 days), and ICU admission tended to be less frequent in the step-down group (P=0.13).

Citation(s):

Creemers-Schild D et al. Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim–sulfamethoxazole: Lessons from an observational cohort study. Infection 2015 Oct 15; [e-pub].