Trimethoprim

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It is taken by mouth. Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It is taken by mouth. Common side effects include nausea, changes in taste, and rash. Rarely it may result in blood problems such as not enough platelets or white blood cells. May cause sun sensitivity. There is evidence of potential harm during pregnancy in some animals but not humans. It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death. Trimethoprim was first used in 1962. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication and is not very expensive. In the United States, ten days of treatment costs about $21. It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species. It may also be used to treat and prevent Pneumocystis jirovecii pneumonia. It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea). Trimethoprim has been used in trials to treat retinitis. Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries. Cultures and susceptibility tests should be done to make sure bacteria is treated by trimethoprim. 10-20% of trimethoprim is metabolized by the liver and the rest is excreted in the urine. Therefore, trimethoprim should be used with caution in individuals with kidney and liver impairments. Dosage adjustment is not needed for liver impairment but should be adjusted for kidney impairment. Based on studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy. It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy. Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis. Trimethoprim's affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase. Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance. This benefit has been questioned.