Treatment of Pneumocystis pneumonia with intermediate-dose and step-down to low-dose trimethoprim–sulfamethoxazole: lessons from an observational cohort study

BACKGROUND: The recommended treatment of Pneumocystis jirovecii pneumonia (PCP) is high-dose trimethoprim–sulfamethoxazole (TMP–SMX) in an equivalent of TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day for 2 or 3 weeks. High rates of adverse events are reported with this dose, which raises the question if lower doses are possible. METHODS: All adult patients diagnosed with PCP in various immune dysfunctions and treated with TMP–SMX between January 1, 2003 and July 1, 2013 in a tertiary university hospital were included. Per institutional protocol, patients initiated treatment on intermediate-dose TMP–SMX (TMP 10–15 mg/kg/day) and could be stepped down to low-dose TMP–SMX (TMP 4–6 mg/kg/day) during treatment. Clinical variables at presentation, relapse rate and mortality rates were compared between intermediate- and step-down treatment groups by uni- and multivariate analyses. RESULTS: A total of 104 patients were included. Twenty-four patients (23 %) were switched to low-dose TMP–SMX after a median of 4.5 days (IQR 2.8–7.0 days). One relapse (4 %) occurred in the step-down group versus none in the intermediate-dose group. The overall 30-day mortality was 13 %. There was 1 death in the step-down group (4 %) compared to 13 deaths (16 %) in the intermediate-dose group. CONCLUSIONS: We observed high cure rates of PCP by treatment with intermediate-dose TMP–SMX. In addition, a step-down strategy to low-dose TMP–SMX during treatment in selected patients appears to be safe and does not compromise the outcome of treatment.