Toxoplasma

Antimicrobial	Mode of action	Metabolism	Adverse effects	Recommended dosage (immunocompromised)	Recommended dosage (immunocompetent)
Pyrimethamine (Daraprim) oral	Inhibits folic acid synthesis	Readily absorbed by gut; hepatic metabolism, lipid soluble	Cytopenias, rash, GI intolerance	Acute: loading dose 200 mg then 50–75 mg daily; with oral folinic acid (leucovorin) 10–20 mg/d Maintenance: 25–50 mg/day with oral folinic acid 10–25 mg/d	Loading dose 200 mg daily for 2 d, then 50–75 mg daily for 2–4 wk; with oral folinic acid 10–20 mg/d
plus
Sulfadiazine ^a oral	Inhibits folic acid synthesis; acts synergistically and sequentially with pyrimethamine	Readily absorbed by the gut; penetrates blood–brain barrier; some hepatic metabolism	GI intolerance, rash (Stevens–Johnson syndrome), cytopenias, nephrolithiasis, crystalluria, interstitial nephritis, encephalopathy	Acute: 1–1.5 g q6h Maintenance: 500–1000 mg/day QID	1–1.5 g q6h, 2–4 wk
or
Clindamycin^a oral and IV	Unknown; possibly inhibition of plastid and/or mitochondrial protein synthesis	Readily absorbed by gut; excellent tissue penetration	GI intolerance, rash, pseudomembranous colitis	Acute: 600 mg q6h (up to IV 1200 mg q6h) Maintenance: 300–450 mg PO q6–8h	300 mg q6h, 4 wk, repeat as needed

Abbreviation: GI = gastrointestinal.

^a Used in combination with pyrimethamine.

Adapted from Mofenson et al. MMWR Recomm Rep. 2004;53(RR–14):1.

For ocular toxoplasmosis, the drugs of choice are pyrimethamine and sulfadiazine or trisulfapyrimidine with folinic acid in the same dosages as described earlier. Therapy is given for 4 weeks and repeated as needed. Treatment is required to prevent relapse with the risk of progressive vision loss and other complications such as glaucoma. Adjunctive therapy with systemic corticosteroids (prednisone, 80 to 120 mg/day, or an equivalent) is indicated if the macula, optic nerve, or papillomacular bundle is involved.

Immunocompromised host

For TE, the combination of pyrimethamine, 200 mg loading dose in two divided doses followed by 50 to 75 mg/day orally, plus sulfadiazine, 4 to 6 g/day orally in four doses, remains the mainstay of treatment (see Table 199.1). Oral folinic acid is added to preclude the hematologic toxicities associated with antifolate agents. Acute therapy is recommended for at least 6 weeks. Longer treatment durations may be needed if there is extensive clinical and radiographic disease or the response is incomplete at 6 weeks. Patients who cannot tolerate sulfas can be given clindamycin in combination with pyrimethamine as described. Prophylactic use of anticonvulsants is not recommended. Corticosteroids should not be used routinely but are indicated if there is evidence of increased intracranial pressure. In one study, 70% of AIDS patients treated for TE had a quantifiable clinical improvement by day 7 of therapy. Conversely, patients not responding to empiric therapy had evidence of progressive disease within the first 10 days. Ninety percent of patients had improvement on neuroradiographic studies within 6 weeks of starting therapy.

In immunocompromised hosts, maintenance therapy (secondary prophylaxis) should be initiated. The regimen is usually the same as that used for primary treatment but at half dose. Maintenance therapy should be continued for the life of the patient or until the underlying immunosuppression has resolved. In patients with AIDS, secondary prophylaxis can be discontinued if they have sustained CD4 counts greater than 200 cells/mm³ for longer than 6 months.

The same chemotherapeutic regimens are used for extraneural toxoplasmosis; however, there are limited data available on the optimal length and outcome of treatment. As a rule, ocular toxoplasmosis responds favorably to therapy, and treatment of pulmonary infection has been reported to be successful in 50% to 77% of patients.

Intravenous trimethoprim–sulfamethoxazole (TMP–SMX, Bactrim, Septra), at 5 mg/kg/day trimethoprim component, has been used when oral therapy is contraindicated. Although TMP–SMX is available for oral use, response rates have been lower than standard regimens. Recently, trials have shown higher initial response rates when the dose was increased (trimethoprim, 6.6 to 10 mg/kg body weight per day).

The drugs described thus far are active only against the tachyzoite form of T. gondii. Surviving tissue cysts can reinitiate TE and other manifestations of reactivated latent disease if treatment is discontinued. Therefore it is necessary to give long-term suppressive therapy. Pyrimethamine, 25 to 50 mg/day, and sulfadiazine, 2 to 4 g/day orally in four doses, with 10 mg/day of oral folinic acid is recommended because of the low relapse rate associated with this combination.

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