Toxicity and effectiveness of low-dose and conventional-dose co-trimoxazole for treatment of Pneumocystis jirovecii pneumonia in Christchurch, New Zealand: a retrospective cohort study

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection which primarily affects immunocompromised individuals. The recommended dose of co-trimoxazole for treatment of PJP is 15–20 mg/kg/day of the trimethoprim component based on an underpowered 1975 study in 20 children with cancer. While this dose is effective, a lower dose may be sufficient and cause less toxicity. We conducted a retrospective cohort study of patients treated for ‘proven’ or ‘probable’ PJP at Christchurch Public Hospital, New Zealand between January 2018 and November 2023. We compared treatment limiting adverse drug reactions (ADR) and 30-day all-cause mortality in patients initiated on a conventional dose of co-trimoxazole (≥12.5 mg/kg/day) versus those initiated on a low dose of co-trimoxazole (<12.5 mg/kg/day). A total of 148 patients with a positive Pneumocystis jirovecii PCR or immunofluorescence result were treated with co-trimoxazole of whom 139 were categorised as having ‘proven’ or ‘probable’ PJP (36 low-dose (25.9%), 103 conventional-dose (74.1%)). A higher proportion of patients receiving conventional-dose co-trimoxazole required a treatment alteration due to an ADR (43.7%, 45/103) than patients receiving low-dose co-trimoxazole (16.7%, 6/36). There was no statistically significant difference in 30-day all-cause mortality between the low- and conventional-dose groups (adjusted hazard ratio for low- versus conventional-dose = 0.76, 95% confidence interval 0.29–1.98, p = 0.57). In this comparatively large retrospective cohort, low-dose co-trimoxazole was associated with fewer treatment-limiting ADRs without an observed increase in mortality. These findings add to the growing body of observational evidence supporting the use of lower co-trimoxazole doses for the treatment of PJP. This large observational study demonstrated that low-dose co-trimoxazole was associated with fewer treatment-limiting ADRs than conventional dose regimens. No statistically significant mortality difference was observed. These findings add to the growing body of evidence supporting lower co-trimoxazole doses for PJP.