Toxoplasmosis treatment

Deron Z, Jablkowski M. Objawy uboczne w przebiegu lec-zenia toksoplazmozy. [Side effects of toxoplasmosis treatment.] Pol Tyg Lek 1980 35(23) 857-9. 

The sulfas also remain clinically useful in the treatment of chancroid, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and the fungus-related nocardiosis (7). In combination with pyrimethamine, they are recommended for toxoplasmosis (8) and have been used for chloroquine-resistant falciparium malaria (4,9). There has also been some use of sulfas for the prophylaxis of rheumatic fever. The sulfone, dapsone, remains an accepted treatment for all forms of leprosy (4). 

Other Infections. The slowly excreted sulfonamides (eg, sulfamethoxypyrida2ine, sulfadimethoxine) are used for treatment of minor infections such as sinusitis or otitis, or for prolonged maintenance therapy. Soluble sulfonamides are sometimes used for proto2oal infections in combination with other agents. Pyrimethamine, combined with sulfonamides, has been used for toxoplasmosis or leishmaniasis, and trimethoprim with sulfonamides has been used in some types of malaria. In nocardiosis, sulfonamides have been used with cycloserine [68-41-7] (17). 

Spiramycin is another macrolide, recently introduced into medicine for the treatment of toxoplasmosis, infections caused by the protozoan Toxoplasma gondii. This contains a 16-membered lactone ring (erythromycin has a 14-membered ring), and two aminosugars, o-mycaminose and o-forosamine. o-Forosamine is remarkable in having only one hydroxyl group, and that is bound up in the hemiacetal ring system. 

Dapsone (p. 280) has several therapeutic uses besides treatment of leprosy, it is used for prevention/prophylaxis of malaria, toxoplasmosis, and actinomycosis. 

Infants (younger than 2 months of age) - Contraindicated, except as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis. 

Used for malaria chemoprophylaxis and treatment the dihydrofolate reductase inhibitors do not cause pharmacological side-effects in the host. In the higher dose used for toxoplasmosis macrocytic anaemia and other adverse effects may occur. 

The treatment of choice for toxoplasmosis is pyrimethamine with sulfadiazine a folate supplement is also given to counteract the megaloblastic... 

Sulfonamides, such as sulfadiazine, in combination with pyrimethamine, are considered the treatment of choice of symptomatic toxoplasmosis. Patients should be well hydrated to prevent crystalluria this problem may be reduced with the use of triple sulfas (trisulfapyrimidine). Some regimens have included a sulfonamide (sul-fadoxine) in combination with pyrimethamine (Fansidar) for the treatment of chloroquine-resistant malaria caused by P. falciparum. 

In addition to its antimalarial effects, pyrimethamine is indicated (in combination with a sulfonamide) for the treatment of toxoplasmosis. The dosage required is 10 to 20 times higher than that employed in malarial infections. 

Unlabeled Uses Treatment of actinomycosis, babesiosis, erysipelas, malaria, otitis media, Pneumocystis carinii pneumonia, sinusitis, toxoplasmosis... 

It is used in the treatment of severe anaerobic infections caused by bacteroides and other anaerobes. It is also used in combination with aminoglycoside in the treatment of abdomen and GIT wounds, infections of female genital tract, pelvic abscesses, aspiration pneumonia and septic abortion. It is also used for prophylaxis of endocarditis. It is also used along with primaquine in Pneumocystis carinii pneumonia in AIDS patients and with pyrimethamine for toxoplasmosis. 

The combination is indicated in chloro-quine resistant malaria and prophylaxis. Pyrimethamine-sulfadiazine combination is used for treatment of toxoplasmosis. 

Clindamycin is indicated for the treatment of skin and soft-tissue infections caused by streptococci and staphylococci. It is often active against community-acquired strains of methicillin-resistant S aureus, an increasingly common cause of skin and soft tissue infections. Clindamycin is also indicated for treatment of anaerobic infection caused by bacteroides and other anaerobes that often participate in mixed infections. Clindamycin, sometimes in combination with an aminoglycoside or cephalosporin, is used to treat penetrating wounds of the abdomen and the gut infections originating in the female genital tract, eg, septic abortion and pelvic abscesses and aspiration pneumonia. Clindamycin is now recommended rather than erythromycin for prophylaxis of endocarditis in patients with valvular heart disease who are undergoing certain dental procedures. Clindamycin plus primaquine is an effective alternative to trimethoprim-sulfamethoxazole for moderate to moderately severe Pneumocystis jiroveci pneumonia in AIDS patients. It is also used in combination with pyrimethamine for AIDS-related toxoplasmosis of the brain. 

Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade (Figure 46-2). The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. 

Pyrimethamine and sulfadiazine have been used for treatment of leishmaniasis and toxoplasmosis. In falciparum malaria, the combination of pyrimethamine with sulfadoxine (Fansidar) has been used (see Chapter 52). 

Pyrimethamine, in combination with sulfadiazine, is first-line therapy in the treatment of toxoplasmosis, including acute infection, congenital infection, and disease in immunocompromised patients. For immunocompromised patients, high-dose therapy is required followed by chronic suppressive therapy. Folinic acid is included to limit myelosuppression. Toxicity from the combination is usually due primarily to sulfadiazine. The replacement of sulfadiazine with clindamycin provides an effective alternative regimen. 

Antibiotics also are active against other protozoans. Tetracycline and erythromycin are alternative therapies for the treatment of intestinal amebiasis. Clindamycin, in combination with other agents, is effective therapy for toxoplasmosis, pneumocystosis, and babesiosis. Spiramycin is a macrolide antibiotic that is used to treat primary toxoplasmosis acquired during pregnancy. Treatment lowers the risk of the development of congenital toxoplasmosis. 

Clinical Use. Atovaquone (Mepron) is used primarily to treat the protozoon that causes toxoplasmosis and the fungus that causes pneumocystis pneumonia in immunocompromised patients.6 This drug is not typically the primary treatment for pneumocystis, but is often reserved for patients who cannot tolerate more traditional treatments using sulfamethoxazole and trimethoprim (see Chapter 34) or pentamidine (see later). Atovaquone can also be used to prevent and treat resistant cases of malaria, and the antimalarial effects of this drug seem especially useful when combined with proguanil.48... 

One of the most common infections in man is caused by the protozoan, Toxoplasma gondii, which is transmitted to humans when they consume raw or inadequately cooked, infected meat. Infected pregnant women can transmit the organism to the fetus. Cats are the only animals that shed oocysts that can infect other animals as well as man. The treatment of choice for this condition is the antifolate drug, pyrimethamine [peer i METH a meen] (see p. 353). A combination of sulfadiazine (see p. 289) and pyrimethamine is also efficacious. Leucovorin is often administered to protect against folate deficiency. Other inhibitors of folate biosynthesis, such as trimethoprim (see p. 293) and sulfamethoxazole (see p. 289) are without therapeutic efficacy in toxoplasmosis. [Note At the first appearance of a rash, pyrimethamine should be discontinued since hypersensitivity to this drug can be severe.]... 

It should be noted that a recent, evidence-based, systematic review of published randomized clinical trials of therapy for toxoplasmic retinochoroiditis fitund only three studies that met the authors criteria for inclusion, two of which were carried out more than 35 years ago. Based on this evaluation the authors concluded that there was a lack of evidence to support routine antibiotic treatment for ocular toxoplasmosis, finding no evidence for a beneficial effect on the duration and severity of signs of the disease process. However, the preponderance of evidence supports the concept that appropriate antibiotic therapy is a community standard of care, which is bolstered by guidelines for treatment in many published sources, plus the responses of those practitioners recently surveyed about their preferred patterns of management of the condition. 

Two other agents show promise in treatment of ocular toxoplasmosis. Atovaquone, primarily used for mild to moderate episodes of Pneumocystis carinii pneumonia, has been effective in small series of patients with toxoplasmosis. It appears to have activity against both tachy-zoites and tissue cysts. More recent studies on atovaquone in toxoplasmosis are limited to murine models, and no further reports on this drug therapy in humans have been published. Azithromycin, a macrolide antibiotic, is efficacious against T. gondii and can also kill tissue cysts. A randomized study of 46 patients compared the combinations of azithromycin plus pyrimethamine versus pyrimethamine plus sulfadiazine in treatment of ocular toxoplasmosis efficacy was similar, but the azithromycin/ pyrimethamine regimen caused less adverse effects. 

Differential diagnosis of ocular toxocariasis includes retinoblastoma (frequently confused with toxocariasis). Coats disease, persistent hyperplastic primary vitreous, retinopathy of prematurity, femilial exudative vitreo-retinopathy, intermediate uveitis, toxoplasmosis, and idiopathic subretinal neovascular membranes. Because toxocariasis frequently mimics retinoblastoma, differential diagnosis is critical, because their treatments are radically different. 

Bosch-Driessen LH, Verbraak ED, Suttorp-Schulten MS, et al. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfediazine for the treatment of ocular toxoplasmosis. Am J Ophthalmol 2002 134 34. 

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