• Pyrimethamine 200 mg PO once, followed by dose based on body weight (AI):
  • Body weight ≤60 kg: pyrimethamine 50 mg PO daily plus sulfadiazine 1,000 mg PO every 6 hours plus leucovorin 10–25 mg PO daily (can increase to 50 mg daily or twice daily)
  • Body weight >60 kg: pyrimethamine 75 mg PO daily plus sulfadiazine 1,500 mg PO every 6 hours plus leucovorin 10–25 mg PO daily (can increase to 50 mg daily or twice daily)

or

• Trimethoprim-Sulfamethoxazole (trimethoprim 5 mg/kg and sulfamethoxazole 25 mg/kg) (IV or PO) twice daily (AII)

Note: if pyrimethamine is unavailable or cannot be obtained without delay due to cost or other factors, trimethoprim-sulfamethoxazole should be used in place of pyrimethamine plus sulfadiazine (AII).

• (Pyrimethamine plus leucovorin)^a plus clindamycin 600 mg IV or PO every 6 hours (AI); preferred alternative for patients intolerant of sulfadiazine or who do not respond to pyrimethamine-sulfadiazine; must add additional agent for PCP prophylaxis (AII), or
• Atovaquone^b 1,500 mg PO twice daily plus (pyrimethamine + leucovorin)^a (BII), or
• Atovaquone^b 1,500 mg PO twice daily plus sulfadiazine^c (BII), or
• Atovaquone^b 1,500 mg PO twice daily (BII)
• For patients with a history of sulfa allergy, rapid sulfa desensitization may be attempted using one of several published strategies (BI).
• During the desensitization phase, atovaquone 1,500 mg PO should be administered twice daily until therapeutic doses of trimethoprim-sulfamethoxazole (trimethoprim 5 mg/kg and sulfamethoxazole 25 mg/kg) twice daily are achieved (CIII).

• At least 6 weeks (BII); longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks
• After completion of the acute therapy, all patients should be continued on chronic maintenance therapy

• Adjunctive corticosteroids (e.g., dexamethasone) should only be administered when clinically indicated to treat a mass effect associated with focal lesions or associated edema (BIII) or for control of clinically significant immune reconstitution inflammatory syndrome (IRIS) symptoms in conjunction with antiretroviral therapy and anti-toxoplasma therapy (CIII); discontinue as soon as clinically feasible. For patients in whom the diagnosis of toxoplasma encephalitis is presumptive based in part on clinical response, one needs to be careful as central nervous system lymphoma may also respond to steroids clinically and radiologically.
• Antiseizure medications should be administered to patients with toxoplasma encephalitis and associated seizures (AII) and continued through at least the period of acute treatment (BII); antiseizure medications should not be used as prophylaxis in patients without seizures (BII).