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Trimethoprim (TMP) is an antibiotic used mainly in the treatment of uncomplicated urinary tract infections. Trimethoprim is also used in the treatment of travelers' diarrhea and pediatric patient middle ear infections. With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS. It works to selectively inhibit the bacterial dihydrofolate reductase used in folate synthesis, which leads to folate depletion and bacterial death. Trimethoprim is available both as an oral tablet and oral solution. The tablet form is available as a generic medication. Primsol, the oral solution, is currently the only FDA-approved liquid solution of trimethoprim.

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.

Trimethoprim began to be used in a clinical setting to treat bacterial infections in 1962. In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland. Trimethoprim is on the World Health Organization's List of Essential Medicines, the important medications needed in a basic health system.

Medical uses
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 jiroveci pneumonia. It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea).

When trimethoprim used alone for urinary tract infections, resistance quickly developed. Therefore, it's rarely used alone.

Spectrum of susceptibility
Cultures and susceptibility tests should be carried out to determine the susceptibility of the bacteria causing the infection to trimethoprim. The MIC range for susceptible bacteria strains are,
 * Escherichia coli: 0.05-0.1 μg/ml
 * Proteus mirabilis: 0.5-1.5 μg/ml
 * Klebsiella pneumoniae: 0.5-5.0 μg/ml
 * Enterobacter species: 0.5-5.0 μg/ml
 * Coagulase-negative Staphylococcus species, including S. saprophyticus: 0.15-5.0 μg/ml
 * Streptococcus pneumoniae: 1-4 μg/ml
 * Haemophilus influenzae: 0.06-0.5 μg/ml

Common
Common side effects include:
 * Nausea
 * Change in Taste
 * Vomiting
 * Diarrhea
 * Rash
 * Itchiness

Rare

 * Trimethoprim can cause thrombocytopenia (low levels of platelets) by lowering folic acid levels; this may also cause megaloblastic anemia.
 * Trimethoprim antagonizes the epithelial sodium channel in the distal tubule, thus acting like amiloride.  This can cause hyperkalemia.
 * Trimethoprim also competes with creatinine for secretion into the renal tubule. This can cause an artificial rise in the serum creatinine.
 * Use in EHEC infections may lead to an increase in expression of Shiga toxin.

Contraindications
Contraindications include the following:
 * known hypersensitivity to trimethoprim
 * history of megaloblastic anemia due to folate deficiency

Renal and Hepatic Impairment
The metabolism of trimethoprim consists of 10-20% mainly by the liver whereas the remainder is excreted unchanged in the urine. Therefore, trimethoprim should be used with caution in patients with renal and hepatic impairment. Hepatic dosage adjustment is not provided. However for patients with a creatinine clearance 15 to 30 mL/min, the dose should be decreased. Trimethoprim is not recommended for patients with creatinine clearance less than 15 mL/min.

Pregnancy
Based on recent studies, since 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.

Mechanism of action
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 synthetase, an enzyme involved further upstream in the same pathway. Trimethoprim and sulfamethoxazole are commonly used in combination due to claimed synergistic effects, and reduced development of resistance. This benefit has been questioned.