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AI-Generated response:

What antibiotics are used to treat congenital toxoplasmosis?

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

The antibiotics used to treat congenital toxoplasmosis are pyrimethamine, sulfadiazine, and leucovorin.

Pyrimethamine should be used cautiously due to potential bone marrow suppression, and it is contraindicated in patients with known hypersensitivity or megaloblastic anemia due to folate deficiency.[1-4]

  • Pyrimethamine is administered orally, starting with a loading dose followed by a maintenance dose, often in combination with sulfadiazine and leucovorin to enhance efficacy and mitigate side effects like bone marrow suppression.[1-4]

  • Sulfadiazine is used in combination with pyrimethamine and is dosed based on patient weight and age, with specific adjustments for neonates and infants.[1-3]

  • Leucovorin is added to counteract the potential hematologic toxicity of pyrimethamine, particularly folate antagonism, and is dosed several times weekly.[1-3]

  • Treatment duration for congenital toxoplasmosis typically extends for one year to ensure comprehensive management of the infection.[1-3]

  • In cases involving severe chorioretinitis or high CSF protein levels, adjunctive therapy with prednisone may be considered, although its efficacy in this context is not well established.[2-3]

Additional info

It is crucial to monitor patients closely for side effects, especially hematologic effects like neutropenia and anemia, which can be mitigated by the concurrent administration of leucovorin. Regular blood tests are recommended to monitor the patient's blood counts and to adjust the medication doses if necessary. The combination of pyrimethamine, sulfadiazine, and leucovorin is supported by guidelines and clinical practice for the effective treatment of congenital toxoplasmosis, aiming to prevent or reduce the severity of long-term sequelae such as neurological damage or vision loss. Early and adequate treatment has been associated with better outcomes, emphasizing the importance of timely diagnosis and management.

References

Reference 1

1.

Elsevier ClinicalKey Drug Monograph

Content last updated: February 5, 2024.

Indications And Dosage Treatment is usually continued for 1 year. **for the treatment of congenital toxoplasmosis** Oral dosage Infants and Children: 75 mg/kg PO as a single dose, followed by 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin is recommended for infants/older children diagnosed beyond the neonatal period with active disease (chorioretinitis) by the American Academy of Pediatrics (AAP) guidelines. Continue treatment for at least 1 to 2 weeks after resolution of signs and symptoms and for 4 to 6 weeks total. Neonates: 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin is recommended by the American Academy of Pediatrics (AAP) guidelines. Treatment is usually continued for 1 year.

Reference 2

2.

Elsevier ClinicalKey Clinical Overview

Treatment For infections acquired at or after 18 weeks of gestation or if fetal infection is confirmed through amniocentesis, use pyrimethamine, leucovorin, and sulfadiazine in place of spiramycin Treat HIV-positive pregnant patients who have CD4 cell counts lower than 200 cells/mm³ with trimethoprim-sulfamethoxazole late in second and third trimesters to prevent reactivation and the (rare) possibility of transmission to the fetus Avoid trimethoprim in the first trimester, if possible, because it is a folic acid antagonist Congenital infection: Recommended for infected neonates for 12 months Treatment also consists of regimen of pyrimethamine, sulfadiazine, and leucovorin

Treatment Sulfadiazine Oral tablet; Neonates: 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin recommended by AAP guidelines; treatment should continue for 1 year. Sulfadiazine Oral tablet; Infants and Children: 75 mg/kg PO as single dose, followed by 50 mg/kg/dose PO twice daily in combination with pyrimethamine and leucovorin for infants/older children diagnosed beyond the neonatal period with active disease (chorioretinitis) recommended by AAP guidelines . Continue treatment for at least 1 to 2 weeks after resolution of signs and symptoms and for 4 to 6 weeks total. Leucovorin Leucovorin Calcium Oral tablet; Neonates: 10 mg PO 3 times weekly in combination with pyrimethamine and sulfadiazine for 1 year. Leucovorin Calcium Oral tablet; Infants and Children: 10 to 20 mg PO 3 times weekly in combination with pyrimethamine and sulfadiazine for at least 1 to 2 weeks after resolution of signs and symptoms and a total of 4 to 6 weeks. Prednisone Prednisone Oral tablet; Neonates: 0.5 mg/kg/dose PO twice daily in combination with pyrimethamine, sulfadiazine, and leucovorin recommended for patients with CSF protein 1 g/dL or more or severe chorioretinitis in vision-threatening macular area. Initiate after 72 hours of anti-Toxoplasma therapy and continue until CSF protein is less than 1 g/dL or resolution of severe chorioretinitis.

Treatment Sulfadiazine Oral tablet; Adolescents: 2 to 4 g PO daily divided in 2 to 4 doses in combination with pyrimethamine and leucovorin, or alternatively with atovaquone, recommended by HIV guidelines. Sulfadiazine Oral tablet; Adults: 2 to 4 g PO daily divided in 2 to 4 doses in combination with pyrimethamine and leucovorin, or alternatively with atovaquone, recommended by HIV guidelines. Leucovorin Leucovorin Calcium Oral tablet; Infants and Children: 5 mg PO every 3 days in combination with pyrimethamine and sulfadiazine or clindamycin. Leucovorin Calcium Oral tablet; Adolescents: 10 to 25 mg PO once daily in combination with pyrimethamine and sulfadiazine or clindamycin. Leucovorin Calcium Oral tablet; Adults: 10 to 25 mg PO once daily in combination with pyrimethamine and sulfadiazine or clindamycin. For management of ocular disease Pyrimethamine Pyrimethamine Oral tablet; Infants and Children: 2 mg/kg PO once on day 1, followed by 1 mg/kg PO daily. Used in combination with sulfadiazine and leucovorin for at least 4 to 6 weeks. Pyrimethamine Oral tablet; Adults: 100 mg PO once on day 1, followed by 25 to 50 mg PO daily. Used in combination with sulfadiazine and leucovorin for at least 4 to 6 weeks. Sulfadiazine Sulfadiazine Oral tablet; Infants and Children: 50 mg/kg PO twice daily. Used in combination with pyrimethamine and leucovorin for at least 4 to 6 weeks. Sulfadiazine Oral tablet; Adults: 2 to 4 grams PO daily for 2 days, followed by 500 mg to 1 g PO four times per day.

Reference 3

3.

McLeod, Rima, Boyer, Kenneth M. (2025). Toxoplasmosis (Toxoplasma gondii). In Nelson Textbook of Pediatrics (pp. 2186). DOI: 10.1016/B978-0-323-88305-4.00336-9

Delay in maternal treatment during gestation results in greater brain and eye disease in the infant. Diagnostic amniocentesis should be performed at >17-18 weeks of gestation in pregnancies when there is high suspicion of fetal infection. After 24 weeks of gestation, incidence of transmission is relatively high, and all pregnant women who are infected acutely after that time are treated with pyrimethamine, sulfadiazine, and leucovorin to treat the fetus. The approach in France to congenital toxoplasmosis includes systematic serologic screening of all pregnant women beginning at ≤11 weeks of gestational age. For women who are seronegative, testing is performed again each month during gestation, at birth, and 1 month after birth. Mothers with acute infection early in gestation and without evidence of involvement of the fetus are treated with spiramycin to prevent transmission and sulfadiazine and pyrimethamine to treat possible fetal infection. Ultrasonography and amniocentesis for PCR at approximately week 17-18 of gestation are used for fetal diagnosis and have 97% sensitivity and 100% specificity. Confidence intervals for sensitivity are larger early and late in gestation. Fetal infection is treated with pyrimethamine, sulfadiazine, and leucovorin after 14 weeks of gestation, and termination of pregnancy is very rare at present. Prompt initiation of treatment with pyrimethamine, sulfadiazine, and leucovorin during pregnancy usually results in an excellent outcome, with normal development of children in most cases. Only 19% of infants have findings of congenital infection, including intracranial calcifications (13%) and chorioretinal scars (6%), although the prevalence of chorioretinal scars is 39% at follow-up later in childhood. Several studies have demonstrated improved outcomes with shorter times between diagnosis and initiation of treatment.

All fetuses and newborns infected withT. gondiishould be treated regardless of whether they have clinical manifestations of infection, because treatment may be effective in interrupting acute disease that damages vital organs (seeTable 336.2). The fetus is treated by treating the pregnant woman with pyrimethamine, sulfadiazine, and leucovorin after the first trimester. Infants should be treated for 1 year with pyrimethamine (2 mg/kg/day orally [PO] bid for 2 days, then 1 mg/kg/day for 2-6 months, and then 1 mg/kg given on Monday, Wednesday, and Friday), sulfadiazine (100 mg/kg/day PO bid), and leucovorin (5-10 mg PO given on Monday, Wednesday, and Friday, or more often depending on neutrophil count). The relative efficacy in reducing sequelae of infection and the safety of treatment with 2 months vs 6 months of the higher dosage of pyrimethamine are being compared in the U.S. National Collaborative Study. (Updated information about this study and these regimens is available from Dr. Rima McLeod, 773-834-4131.) Pyrimethamine and sulfadiazine are available only in tablet form but can be prepared as suspensions.Prednisone(1 mg/kg/day PO bid) has been used in addition when active chorioretinitis involves the macula or otherwise threatens vision or when the CSF protein is >1,000 mg/dL at birth, but the efficacy of this adjunctive therapy is not established. Prednisone is continued only for as long as the active inflammatory process in the posterior pole of the eye is vision-threatening or the CSF protein is >1,000 mg/dL and is then tapered rapidly if the duration of treatment has been brief.

Reference 4

4.

Food and Drug Administration (DailyMed).

Publish date: July 6, 2021.

Pediatric Use Pediatric Use: See DOSAGE AND ADMINISTRATION section.

Indications And Usage INDICATIONS AND USAGE Treatment of Toxoplasmosis: Pyrimethamine is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination.

Contraindications CONTRAINDICATIONS Use of pyrimethamine is contraindicated in patients with known hypersensitivity to pyrimethamine or to any component of the formulation. Use of the drug is also contraindicated in patients with documented megaloblastic anemia due to folate deficiency.

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