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Toxoplasmosis: Treatment & Medication
Updated: Dec 20, 2007
- Overview
- Differential Diagnoses & Workup
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Treatment
Emergency Department Care
- Care of the patient in the ED should be specific to the presenting manifestations of the disease.
- Adequate airway, breathing, and circulation must be assessed and treated accordingly.
- Adequate fluid resuscitation, pain control, and fever control must be ensured.
- Neuroimaging should be considered for an immunocompromised patient with new neurologic deficit, cranial nerve abnormality, or altered mental status.
- See Medication for medications regimens.
Consultations
Subspecialty consultation is required for the seriously ill patient, according to organ-specific involvement.
Medication
- Nonpregnant patients
- 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 (10-25 mg/d) should be given to all patients to prevent hematologic toxicity of pyrimethamine.
- May substitute sulfadiazine or clindamycin for azithromycin 500 mg daily or atovaquone 750 mg bid in immunocompetent patients or 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
- 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
or
- Pyrimethamine (25 mg/d PO) and sulfadiazine (4 g/d PO) divided bid/qid until delivery
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.
- Suppressive therapy for patients with AIDS is pyrimethamine 50 mg/d PO plus sulfadiazine 1-1.5 g/d PO plus folinic acid 10 mg/d PO for life.
Anti-infectives
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.
Adult
Pregnant patients:
1 g PO tid
If amniotic fluid test result for T gondii is positive:
3 wk of 50 mg/d pyrimethamine PO and 3 g/d sulfadiazine PO divided bid/tid alternating with 3-wk course of spiramycin 1 g tid
Alternatively, 25 mg/d pyrimethamine PO and 4 g/d sulfadiazine PO divided bid/qid until delivery
Add 10-25 mg/d leucovorin PO to prevent bone marrow suppression
Pediatric
50-100 mg/kg/d PO divided bid/qid for 3-4 wk
Decreases bioavailability of carbidopa leading to decrease of levodopa levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
GI toxicity most common adverse effect; IV administration associated with peripheral paresthesias, irritation at injection site, dysesthesia, giddiness, pain, stiffness, burning sensation, and hot flashes; long-term use may result in superinfection; caution in cardiovascular disease, may prolong QT; may elevate LFTs
Pyrimethamine (Daraprim)
Folic acid antagonist that selectively inhibits plasmodial dihydrofolate reductase. Highly selective against plasmodia and T gondii. Does not destroy gametocytes but arrests sporogony in mosquito. Possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. Extend regimens to include suppressive cure through any characteristic periods of early recrudescence and late relapse for at least 6-10 wk in each case.
Folinic acid should be given to all patients to prevent hematologic toxicity of pyrimethamine
Adult
Nonpregnant patients:
100 mg loading dose PO followed by 25-50 mg/d plus either sulfadiazine 2-4 g/d PO divided qid, clindamycin 300 mg PO qid; may substitute azithromycin for 6 wk
May substitute sulfadiazine or clindamycin for azithromycin 500 mg PO qd or atovaquone 750 mg PO bid in immunocompetent patients or patients with history of allergy to the former drugs
Pregnant patients:
50 mg/d PO for 3 wk plus sulfadiazine alternating with 3-wk course of spiramycin 1 g tid or 25 mg/d PO and sulfadiazine 4 g/d PO divided bid/qid until delivery and leucovorin 10-25 mg/d PO to prevent bone marrow suppression
Pediatric
1-2 mg/kg/d PO divided bid for 1-3 d initial; followed by 1 mg/kg/d bid for 4 wk; not to exceed 25 mg/d
Antifolic acids, such as methotrexate and pyrimethamine, may increase risk of bone marrow suppression; discontinue use if signs of folate deficiency develop; lorazepam may cause mild hepatotoxicity
Documented hypersensitivity; megaloblastic anemia resulting from folate deficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Exercise caution with hepatic or renal impairment; may precipitate hemolytic anemia with G-6-PD deficiency, generally in presence of other stressful events
Sulfadiazine (Microsulfon)
Through competitive antagonism of PABA, interferes with microbial growth. Useful in treatment of toxoplasmosis.
Adult
Nonpregnant patients:
2-4 g/d PO divided qid plus 100 mg pyrimethamine loading dose followed by 25-50 mg/d pyrimethamine
Pregnant patients:
3 g/d PO divided bid/tid plus 50 mg/d pyrimethamine PO for 3 wk plus alternating with 3-wk course of spiramycin 1 g tid or 25 mg/d pyrimethamine PO and sulfadiazine 4 g/d PO divided bid/qid until delivery plus leucovorin 10-25 mg/d PO to prevent bone marrow suppression
Pediatric
<2 months: Not recommended
>2 months: 75 mg/kg or 2 g/m2 initial; followed by 150 mg/kg/d or 4 g/m2/d in 4-6 divided doses; not to exceed 6 g/d
May enhance anticoagulant action of warfarin; may enhance anesthetic effects of thiopental; may increase serum phenytoin levels; may decrease cyclosporine concentrations and increase risk of nephrotoxicity
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with impaired renal or hepatic function, or G-6-PD deficiency; adjust dose with renal insufficiency
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.
Adult
Nonpregnant patients:
300 mg PO qid plus 100 mg pyrimethamine loading dose PO followed by 25-50 mg/d pyrimethamine
Pediatric
8-16 mg/kg/d IV/IM divided tid/qid
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose for severe hepatic dysfunction, but no adjustment needed for renal insufficiency; use associated with severe and possibly fatal colitis
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 patients with history of allergy to the former drugs
Adult
500 mg PO qd for 6 wk
Toxoplasmic encephalitis in patients with AIDS: 1200-1500 mg PO qd for 3-6 wk
Pediatric
Not established
May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Site reactions can occur with IV route; bacterial or fungal overgrowth may result from prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function or prolonged QT intervals
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
Adult
750 mg PO bid for 6 wk in nonpregnant immunocompetent patients or patients with history of allergy to alternative drugs
Pediatric
Not established
May increase zidovudine serum levels; coadministration with rifampin or rifabutin may decrease atovaquone levels; atovaquone may decrease levels of TMP-SMZ
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in elderly persons and in hepatic and renal impairment
Antidote, Folic Acid Antagonist
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.
Adult
Nonpregnant and pregnant patients:
10-25 mg/d PO to prevent bone marrow suppression
Pediatric
Administer as in adults
Decreases effect of methotrexate, phenytoin, phenobarbital, and sulfamethoxazole and trimethoprim combinations; increases toxicity of fluorouracil
Documented hypersensitivity; pernicious anemia or vitamin-deficient megaloblastic anemias
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer intrathecally or intraventricularly
More on Toxoplasmosis |
| Overview: Toxoplasmosis |
| Differential Diagnoses & Workup: Toxoplasmosis |
 Treatment & Medication: Toxoplasmosis |
| Follow-up: Toxoplasmosis |
| Multimedia: Toxoplasmosis |
| References |
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References
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Hardman JG, Limbird LE. Protozoal infections. In: Goodman LS, et al, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill; 1992:989.
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Robert-Gangneux F, Gavinet MF, Ancelle T, Raymond J, Tourte-Schaefer C, Dupouy-Camet J, et al. Value of prenatal diagnosis and early postnatal diagnosis of congenital toxoplasmosis: retrospective study of 110 cases. J Clin Microbiol. Sep 1999;37(9):2893-8. [Medline].
Sanford JP, Gilbert DN, Moellering RC. The Sanford Guide to Antimicrobial Therapy. Hyde Park, Vt: Antimicrobial Therapy, Inc; 1997:86-87.
Wong SY, Remington JS. Biology of Toxoplasma gondii. AIDS. Mar 1993;7(3):299-316. [Medline].
Buzoni-Gatel D, Werts C. Toxoplasma gondii and subversion of the immune system. Trends Parasitol. Oct 2006;22(10):448-52. [Medline].
Davaro RE, Thirumalai A. Life-threatening complications of HIV infection. J Intensive Care Med. Mar-Apr 2007;22(2):73-81. [Medline].
Dodds EM. Toxoplasmosis. Curr Opin Ophthalmol. Dec 2006;17(6):557-61. [Medline].
Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. Jun 12 2004;363(9425):1965-76. [Medline].
Further Reading
Keywords
Toxoplasma gondii, T gondii, T gondii infection, toxoplasmosis, ocular toxoplasmosis cat feces, undercooked meat , congenital toxoplasmosis, acquired toxoplasmosis, toxoplasmosis in immunocompromised host, exposure to cats, retinochoroiditis, food-borne disease
