Lower trimethoprim-sulfamethoxazole dose may be safer than standard for P. jirovecii pneumonia
Lower doses of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia may be as effective as the standard dose, but associated with fewer adverse events, according to a meta-analysis published in Open Forum Infectious Diseases.
“Trimethoprim-sulfamethoxazole (TMP-SMX) is an excellent drug for Pneumocystis jirovecii pneumonia (PJP) and was used with great success in the early days of the AIDS epidemic before antiretroviral treatment,” Guillaume Butler-Laporte, MD, of McGill University Health Centre’s department of medicine and division of infectious diseases, told Healio. “However, the dose was chosen somewhat arbitrarily a long time ago and we know that it leads to significant adverse events, which are usually dose dependent — that is, higher doses lead to more toxicity.”
These toxicities included renal failure and bone marrow suppression, according to Butler-Laporte.
“These adverse events were usually manageable for a patient with AIDS, given that these patients were usually young, and with generally good kidney and bone marrow function,” he told Healio. “However, people who are diagnosed with PJP how have diseases that put them at much higher risk for adverse events, including hematologic malignancies and organ transplantation.”
According to Butler-Laporte, several reports suggested outcomes that were equally as good with lower doses of TMP-SMX, which led to the current study.
The researchers conducted a systematic review, searching Medline, Embase and Cochrane Library from inception through March 2019 for peer-reviewed studies that discussed decreased doses of TMP-SMX, defined as 15 mg/kg per day of trimethoprim or less, for the treatment of PJP.
Butler-Laporte and colleagues identified 10 studies; six were included in the meta-analysis. The studies demonstrated no statistically significant difference in mortality (absolute risk difference, -9% in favor of reduced dose; 95% CI, –27% to 8%). Lower doses of TMP-SMX correlated with an 18% (95% CI, –31% to –5%) absolute risk reduction of grade 3 or higher adverse events.
“In carefully chosen patients, lower doses of TMP-SMX are likely to be as efficacious with less adverse events,” Butler-Laporte said. “However, the studies we found are of limited quality, and we need a randomized trial to truly assess the efficacy and safety of reduced TMP-SMX doses before this is recommended for all patients.” – by Caitlyn Stulpin
Disclosures: Butler-Laporte reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.