Toxoplasmosis sulfadiazine

Have a wide spectrum, but use as individual agents is limited by resistance. Common uses include nocardial infections (DOC), simple UT infections (sulfisoxazole), ulcerative colitis (sulfasalazine), trachoma (sulfacetamide, topical), burns (Ag sulfadiazine, topical), and toxoplasmosis (sulfadiazine + pyrimethamine). 

Pyrimethamine in combination with sulfadiazine or trisnlfapyrimidine is the dmg of choice for toxoplasmosis. A synonym of this combined dmg is daraprim. 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

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

Sulfadiazine 1-1.5 g orally or i.v. 6-hourly -f Pyrimethamine 50 to 100 mg orally initially, then 25-50 mg daily Sulfadiazine 500 mg orally 6-hourly or 1 g orally 12-hourly -f Pyrimethamine 25 to 50 mg orally daily Prophylaxis for P. carinii with cotrimoxazole is effective prophylaxis for toxoplasmosis... 

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. 

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

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). 

Sulfadiazine Oral first-line therapy for toxoplasmosis when combined with pyrimethamine... 

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. 

Toxoplasmosis Lymph nodes many organs and tissues Pyrimethamine-sulfadiazine [see antimalarial drugs] other antibacterials [clindamycin] Trimethoprim-sulfamethoxazole another agent [azithromycin, clarithromycin, atovaquone, or dapsone]... 

Pyrimethamine may also be combined with other antimalarials such as artemisinin derivatives, but these regimens should only be used if the malarial parasites are not resistant to the specific drugs in the regimen.13 Pyrimethamine can also be combined with a sulfonamide drug such as dapsone, sulfadiazine, or sulfamethoxazole to treat protozoal infections that cause toxoplasmosis, or fungal infections that cause Pneumocystis pneumonia.These agents are administered orally. 

The sulfas, including co-trimoxazole (sulfamethoxazole plus trimethoprim, see p. 293), are bacteriostatic. These drugs are active against selected enterobacteria, chlamydia, Pneumocystis, and nocardia. Typical clinical applications are shown in Figure 29.3. In addition, sulfadiazine [sul fa DYE a zeen] in combination with the dihydrofolate reductase inhibitor pyrimethamine [py ri METH a meen] is the only effective form of chemotherapy for toxoplasmosis (p. 353). 

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.]... 

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. 

SoheUian M, Sadoughi MM, Ghajarnia M, et al. Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology 2005 112 1876. 

Trichomoniases immunologicaNy normal patient. Pyrimethamine with sulfadiazine for chorioretinitis.and active toxoplasmosis in imimmodeficicnt patients foilnic add is used to counteract the inevitable megaloblastic anaemia. Alternatives include pyrimethamine with clindamycin or clarithromycin or azithromycin Spiramycin for primary toxoplasmosis in pregnant women. Expert advice is essential. Metronidazole or tinidazole is effective... 

Bosch-Driessen LH, Verbraak FD, Suttorp-Schulten MS, van Ruyven RL, Klok AM, Hoyng CB, Rothova A. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis. Am J Ophthalmol 2002 134(1) 34 0. 

In a randomized, open, multicenter study in 46 patients with sight-threatening ocular toxoplasmosis, those who took pyrimethamine + sulfadiazine had significantly more adverse events, especially malaise, than those who took pyrimethamine + azithromycin (8). 

A large bibliography exists from the 1940 s related to crystalluria and acute kidney injury associated with the use of sulfadiazine [1, 10, 11]. Sulfadiazine disappeared from clinical use for a long time until it re-emerged again in the AIDS era. More recently, the number of reports in adults and children has increased substantially because of the use of sulfadiazine and pyrimethamine, as the treatment of choice for cerebral toxoplasmosis associated with AIDS, other immunosuppressive states or specific infections [7, 12-35]. Acute kidney injury secondary to sulfadiazine crystalluria has been also reported in renal transplant patients [36, 37]. 

Figure 1. Sulfadiazine nephrotoxicity (crystalluria and acute renal failure). 35 year old man with AIDS and cerebral toxoplasmosis treated for 33 days with 4-6 g/dayofsulfadiazine.The patient received oral hydration and possibly had an episode of transient renal impairment during days 8-13. By day 29 of treatment, crystalluria, hematuria, flank pain, renal calculi, and acute renal failure developed. Urine was alkalinized late in the course.

With increasing frequency, clindamycin in combination with pyrimethamine is been used as the replacement drug for sulfadiazine in the treatment of cerebral toxoplasmosis. Perhaps this new combination again may send sulfadiazine nephrotoxicity into "oblivion". Nevertheless, until this possibility occurs, primary care physicians should be aware that sulfadiazine can cause renal toxicity and that effective preventive measures are available. 

Pyrimethamine is a folic acid antagonist that for many years has been used as an antimalarial drug [193-195], specially for chloroquine-resistant P. falciparum. Due to its synergistic activity, pyrimethamine also has been used, in combination with sulfadiazine or dapsone for the treatment or prophylaxis of cerebral toxoplasmosis or PCP in patients with AIDS [196]. 

The recommendations for the treatment of EPM using pyrimethamine, trimethoprim and sulfadiazine were originally based on the use of these drugs for the treatment of malaria and toxoplasmosis in humans. Either pyrimethanune or trimethoprim in combination with sulfadiazine or sulfamethoxazole have been used with some success and have gained widespread acceptance as the treatment of choice for EPM. Pyrimethamine and trimethoprim are diaminopyrimidine antimicrobial agents that inhibit dihydrofolate reductase (DHFR see Ch. 2). These agents interfere with... 

The combination of pyrimethamine and sulfadiazine is the most effective regimen for acute therapy of acquired immune deficiency syndrome (AIDS)-related CNS toxoplasmosis. Therapy with this combination should be continued for at least 3 weeks, but 6 weeks of treatment is recommended for more severely ill patients. 

Pyrimethamine inhibits dihydrofolate reductase in Toxoplasma gondii and is used with sulfadiazine in prophylaxis and treatment of toxoplasmosis Figure V-l-3). 

Toxoplasmosis Pyrimethamine + sulfadiazine TMP-SMX is also prophylactic against Pneumocystis carinii in AIDS... 

Sulfadiazine, a sulfonamide antibiotic, is used in rheumatic fever prophylaxis, as an alternative to penicillin, as an adjunctive regimen in treatment of toxoplasmosis, and in uncomplicated attacks of malaria (see also Figure 90). 

The role of spiramycin in the treatment of HIV-associated cryptosporidiosis remains inconclusive and controversial [335, 336]. The drug did hasten clinical recovery and decrease the duration of oocyst excretion in immunocompetent children with cryptosporidial diarrhea [337]. Spiramycin is also used effectively with or without pyrimethamine-sulfadiazine for the treatment of fetal toxoplasmosis [338, 339]. 

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