Pediatric Toxoplasmosis Medication

Wright-Giemsa staining of body fluid sediments of biopsy tissue touch preparations is a rapid and simple method for visualizing the organisms. The currently recommended drugs for T gondii infection act primarily against the tachyzoite form but do not eradicate the encysted form (bradyzoite). Pyrimethamine is the most effective agent and is included in most drug regimens. Leucovorin (folinic acid) should be administered concomitantly to avoid bone marrow suppression. Unless circumstances arise that preclude using more than 1 drug, a second drug, such as sulfadiazine or clindamycin, should be added.

The efficacy of azithromycin, clarithromycin, atovaquone, dapsone, and cotrimoxazole (ie, trimethoprim-sulfamethoxazole) is unclear; therefore, they should be used only as alternatives in combination with pyrimethamine. The most effective available therapeutic combination is pyrimethamine plus sulfadiazine or trisulfapyrimidine (ie, combination of sulfamerazine, sulfamethazine, and sulfapyrazine). These agents are active against tachyzoites and are synergistic when used in combination.

Additional therapy with corticosteroids (prednisone, 1 mg/kg/day) should be considered with markedly elevated CSF protein (>1g/dL) and vision-threatening chorioretinitis.

Class Summary

These agents exert bacteriostatic action through competitive antagonism with para-aminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid (pteroylglutamic acid) are not susceptible to the action of sulfonamides. Resistant strains are capable of using folic acid precursors or preformed folic acid. In serum, these agents exist in 3 forms: free, conjugated (ie, acetylated and possibly others), and protein bound. The free form is considered to be therapeutically active.

Sulfadiazine (Microsulfon)

This is a bacteriostatic agent that acts synergistically with pyrimethamine to treat T gondii.

Class Summary

Protozoal infections occur throughout the world and are a major cause of morbidity and mortality in some regions. Patients who are immunocompromised are especially at risk. Primary immune deficiency is rare, whereas secondary deficiency is more common. Immunosuppressive therapy, cancer and its treatment, HIV infection, and splenectomy may increase vulnerability to infection. Infectious risk is proportional to neutropenia duration and severity. Protozoal infections are typically more severe in immunocompromised patients than in immunocompetent patients.

Dapsone, a sulfone that has been widely used in the treatment of leprosy, has been administered in combination with pyrimethamine for prophylaxis against malaria.

Dapsone with trimethoprim is used as an alternative to trimethoprim-sulfamethoxazole for the treatment of mild to moderate Pneumocystis carinii pneumonia; dapsone alone can be used for prophylaxis. Dapsone and pyrimethamine have also been used in patients with HIV and low CD4+ T-cell counts to prevent T gondii encephalitis.

Dapsone

Mechanism of action similar to that of sulfonamides—competitive antagonists of PABA prevent formation of folic acid, inhibiting growth.

Pyrimethamine (Daraprim)

Pyrimethamine is a folic acid antagonist that selectively inhibits dihydrofolate reductase. It is highly selective against plasmodia and T gondii. Pyrimethamine has a synergistic effect when used conjointly with a sulfonamide to treat T gondii.

Class Summary

These agents inhibit bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clindamycin (Cleocin)

Clindamycin is used as an alternative to sulfonamides. It may be beneficial when used with pyrimethamine in short-term treatment of CNS toxoplasmosis in patients with AIDS.

Class Summary

Azithromycin, which belongs to the azalide subclass of macrolide antibiotics, is administered orally. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring.

Azithromycin (Zithromax, Zmax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms, in that way interfering with microbial protein synthesis. Nucleic acid synthesis is not affected. Azithromycin 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. The drug is used to treat mild to moderate microbial infections.

Spiramycin

Spiramycin is the drug of choice for maternal or fetal toxoplasmosis. It is used as an alternative therapy in other patient populations when pyrimethamine and sulfadiazine cannot be used.

Class Summary

Supplemental folinic acid is coadministered to prevent hematologic adverse effects caused by bone marrow suppression.

Leucovorin

Leucovorin, also called folinic acid, is a derivative of folic acid used with folic acid antagonists, such as sulfonamides and pyrimethamine.