Randomized controlled trial of pyrimethamine plus sulfadiazine versus trimethoprim plus sulfamethoxazole for treatment of toxoplasmic encephalitis in AIDS patients

J Int Assoc Physicians AIDS Care (Chic). Jan-Feb 2008;7(1):11-6. doi: 10.1177/1545109707301244. Epub 2007 May 21.

Abstract

Background: Toxoplasmic encephalitis (TE), caused by Toxoplasma gondii, is common in AIDS patients. TE can result in tissue destruction via massive inflammation and brain abscess formation.

Methods: Randomized controlled trials were performed in AIDS patients to assess which drug regimen was optimally effective for the treatment of TE. AIDS patients with TE were randomly divided into 3 groups that received a 6-week course of either pyrimethamine (50 mg/day or 100 mg/day) plus sulfadiazine (4 g/day) and folinic acid (25 mg/day) or trimethoprim (10 mg/kg/day) plus sulfamethoxazole (50 mg/kg/day) (TMP-SMX), and results were evaluated with respect to clinical response, mortality, morbidity, and serious adverse events. The primary outcome was defined as death in the first 6-week period. The secondary outcome was successful treatment within 6 weeks without severe adverse events, bone marrow suppression, drug-induced rash, or any other event that caused a change in the treatment regimen.

Results: The results from this study showed that in AIDS patients, TE was most successfully treated with the combination of pyrimethamine (50 mg/day) plus sulfadiazidine (4 g/day) and folinic acid (25 mg/day); failure rates were not significantly different among the 3 treatment groups.

Conclusions: Available data suggest that of the currently available options, treatment of TE with pyrimethamine at 50 mg/day plus sulfadiazidine at 4 g/day provides the best primary outcome for AIDS patients with TE; however, because this study was terminated prematurely, we suggest that treatment with intravenous TMP-SMX be further evaluated to determine its efficacy.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / parasitology
  • Adult
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / adverse effects
  • Antiprotozoal Agents / therapeutic use*
  • Drug Therapy, Combination
  • Encephalitis / drug therapy*
  • Encephalitis / parasitology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pyrimethamine / administration & dosage
  • Pyrimethamine / adverse effects
  • Pyrimethamine / therapeutic use*
  • Sulfadiazine / administration & dosage
  • Sulfadiazine / adverse effects
  • Sulfadiazine / therapeutic use*
  • Toxoplasmosis, Cerebral / drug therapy*
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*

Substances

  • Antiprotozoal Agents
  • Sulfadiazine
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Pyrimethamine