Toxoplasmosis in Emergency Medicine Medication

Nonpregnant patients

Immunocompetent, nonpregnant patients typically do not require treatment. Treatment of nonpregnant patients is described below.

• Six-week regimen

  • Pyrimethamine (100 mg loading dose PO followed by 25-50 mg/d) plus sulfadiazine (2-4 g/d divided qid) OR
  • Pyrimethamine (100 mg loading dose PO followed by 25-50 mg/d) plus clindamycin (300 mg PO qid)
  • Folinic acid (leucovorin) (10-25 mg/d) should be given to all patients to prevent hematologic toxicity of pyrimethamine.
  • TMP (10 mg/kg daily) SMX (50 mg/kg/daily) for 4 weeks
• May substitute sulfadiazine or clindamycin for azithromycin 500 mg daily or atovaquone 750 mg bid in immunocompetent patients or in patients with history of allergy to the former drugs
• Consider steroids in patients with radiologic midline shift, clinical deterioration after 48 hours, or elevated intracranial pressure.

Pregnant patients

• The diagnosis of acute infection is often difficult to make during pregnancy, and the administration of empiric antimicrobial therapy is discouraged.
• Substantial controversy exists regarding the efficacy of treatment during pregnancy in terms of reducing the risk of fetal exposure and the subsequent development of clinical disease such as chorioretinitis or CNS abnormalities.
• Controversy also exists regarding the optimal regimen for treating maternally acquired infection. Spiramycin and pyrimethamine-sulfonamide are both used, but given the infrequency of fetal infection and the asymptomatic nature of most fetal infections, treatment effects are difficult to measure. Spiramycin appears to be somewhat more easily tolerated than pyrimethamine-sulfonamide.

  • Spiramycin 1 g PO q8h
  • If amniotic fluid test result for T gondii is positive: 3 weeks of pyrimethamine (50 mg/d PO) and sulfadiazine (3 g/d PO in 2-3 divided doses) alternating with 3-week course of spiramycin 1 g tid for maternal treatment OR
  • Pyrimethamine (25 mg/d PO) and sulfadiazine (4 g/d PO) divided bid/qid until delivery (this agent may be associated with marrow suppression and pancytopenia) AND
  • Leucovorin 10-25 mg/d PO to prevent bone marrow suppression

Patients with AIDS

• Patients with AIDS are treated with pyrimethamine 200 mg PO initially, followed by 50-75 mg/d PO plus folinic acid 10 mg/d PO plus sulfadiazine 4-8 g/d PO for as long as 6 weeks, followed by lifelong suppressive therapy or until immune reconstitution.
• Suppressive therapy for patients with AIDS (CD4 < 100) is pyrimethamine 50 mg/d PO plus sulfadiazine 1-1.5 g/d PO plus folinic acid 10 mg/d PO for life or until immune reconstitution.
• Patients with AIDS, CNS toxoplasmosis, and evidence of midline shift or increased intracranial pressure may also benefit from steroid therapy (see above).
• Diagnosing toxoplasmosis in the absence of definitive tissue or culture evidence may be perilous because serology may be misleading and a false-positive IgM result is somewhat common, as such, empiric therapy should be avoided.

Class Summary

Empiric anti-infective therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Spiramycin (Rovamycine)

DOC for maternal or fetal toxoplasmosis. Alternative therapy in other patient populations when unable to use pyrimethamine and sulfadiazine.

Pyrimethamine (Daraprim)

Folic acid antagonist that selectively inhibits plasmodial dihydrofolate reductase. Highly selective against plasmodia and T gondii. Folinic acid should be given to all patients to prevent hematologic toxicity of pyrimethamine

Sulfadiazine (Microsulfon)

Through competitive antagonism of PABA, interferes with microbial growth. Useful in treatment of toxoplasmosis.

Clindamycin (Cleocin)

As alternative to sulfonamides, may be beneficial when used in combination with pyrimethamine in acute treatment of CNS toxoplasmosis in patients with AIDS.

Azithromycin (Zithromax)

Acts by binding to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected.

Concentrates in phagocytes and fibroblasts as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Treats mild-to-moderate microbial infections.

May substitute sulfadiazine or clindamycin for azithromycin in immunocompetent patients or in patients with history of allergy to the former drugs.

Atovaquone (Mepron)

A hydroxynaphthoquinone that inhibits mitochondrial electron transport chain by competing with ubiquinone at ubiquinone-cytochrome-c-reductase region (complex III). Inhibition of electron transport by atovaquone will result in inhibition of nucleic acid and ATP synthesis in parasites. Atovaquone has shown activity against bradyzoites in animal models of toxoplasmosis.

May substitute sulfadiazine or clindamycin for atovaquone.

Class Summary

These agents are used to replenish folic acid when the patient is being treated with folic acid antagonists.

Leucovorin (Wellcovorin)

Also called folinic acid. Derivative of folic acid used with folic acid antagonists, such as sulfonamides and pyrimethamine.