According to the guidelines for prevention and treatment of Toxoplasmic encephalitis (TE) caused by the protozoan Toxoplasma gondii (T. gondii) in adults and adolescents with human immunodeficiency virus (HIV), the combination of pyrimethamine plus sulfadiazine plus leucovorin is recommended as the preferred regimen for the initial therapy (AI). In patients intolerant or not responding to the first-line regimen, pyrimethamine plus clindamycin plus leucovorin may be considered (AI). Use of pyrimethamine is preferred in the setting of TE mainly due to its characteristic of high penetration into the brain parenchyma, even in the absence of inflammation. [1]
With limited comparative trials, primarily small randomized trials or open-label observational studies (see Table 1), demonstrating similar efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) to pyrimethamine-sulfadiazine, the panel suggests TMP-SMX be utilized in place of pyrimethamine-sulfadiazine or pyrimethamine-clindamycin when pyrimethamine is not readily accessible (BI). Still, optimal regimens in patients who cannot take an oral regimen have yet to be well-established. As such, some specialists prefer to use parenteral TMP-SMX (BI) or oral pyrimethamine plus parenteral clindamycin (CIII) as initial treatment in severely ill patients who require parenteral therapy. [1]
Similar treatment protocols have also been discussed in the setting of toxoplasma disease in pediatric hematopoietic stem cell transplantation (HSCT) patients in compliance with guideline recommendations. In the presence of suspected or confirmed cases, patients should be treated immediately with anti-Toxoplasma therapy with first-line medications, including pyrimethamine, sulfadiazine, and leucovorin. Alternatively, intravenous (IV) TMP-SMX can be used until pyrimethamine becomes available or in patients with poor enteric absorption of oral medications (e.g., due to gastrointestinal graft-versus-host disease). Besides available statements extrapolated from published guidelines, the review article does not provide additional data in terms of comparative efficacy and safety between pyrimethamine, sulfadiazine, and leucovorin, and TMP-SMX. [2], [3]
A meta-analysis published in 2015 compared the efficacies of treatment options for T. gondii infections. The pooled cure rate of pyrimethamine-sulfadiazine (P-S) in TE was found to be 49.8% (95% confidence interval [CI] 38.8% to 60.8%) compared to 59.9% (95% CI 48.9% to 70%) with TMP-SMX. No significant difference was found between the two treatment modalities (p= 0.635). Of note, this analysis was limited to 7 publications utilizing P-S (n= 414 participants) and 3 publications utilizing TMP-SMX (n= 86 participants). [4]
Another meta-analysis published in 2021 evaluated the safety and efficacy of different antibiotic regimens in patients with ocular toxoplasmosis. Only one comparison of TMP-SMX and P-S was included in the analysis, which was derived from the study by Soheilian et al. (see Table 1). In this study, there was found to be no difference between TMP-SMX and P-S for resolution of vitreous inflammation (risk ratio 0.82; 95% CI 0.55 to 1.22). [5]
A review describing the treatment of toxoplasmosis notes that available data from meta-analyses and a limited number of clinical trials have observed no major differences between P-S regimens and TMP-SMX regimens in regard to safety and efficacy. While it is suggested that P-S is the current gold standard for treatment of acute TE in HIV patients, TMP-SMX seems to have similar clinical effectiveness. Regardless, the authors indicate that there has yet to be a regimen found to be superior to P-S. In general, the choice of therapy should be guided by drug availability, tolerability, costs, and the ability of patients to take medications enterally. [6]