Trimethoprim

Trimethoprim is an antibiotic that blocks a specific enzyme, dihydrofolate reductase. This enzyme converts dihydrofolic acid into tetrahydrofolic acid, an essential step in the production of folates within the bacterium. By inhibiting it, trimethoprim halts the bacterial synthesis of folates and then that of nucleic acids. Deprived of these building blocks, the bacterium can no longer multiply.

Its action targets the bacterium far more than our own cells. Trimethoprim has a markedly stronger affinity for bacterial dihydrofolate reductase than for the equivalent human enzyme. This selectivity explains why it attacks the germ while largely sparing the body.

Trimethoprim is used to prevent and treat urinary tract infections, as well as other infections caused by susceptible germs. It is particularly well suited to conditions of the urinary tract, because a substantial share of the drug reaches the urine directly.

After absorption, 40 to 50 percent of the dose is eliminated unchanged in the urine within 24 hours. The active substance therefore concentrates where the urinary infection takes place, which supports its use in this indication. The choice of the molecule always depends on the susceptibility of the germ involved, as assessed by the physician.

For an acute urinary tract infection in adults, the usual dosage is 200 mg twice a day, that is one dose every 12 hours. Trimethoprim can be taken with or without food. In case of nausea, taking it during a meal is acceptable and does not affect its effectiveness.

The peak concentration occurs about 3 hours after the dose, and the half-life is between 10 and 16 hours when kidney function is normal; it lengthens in cases of renal impairment. Taking the doses regularly maintains a stable level in the blood. You should not change the dose or stop the treatment on your own initiative, even when the symptoms fade: it is the physician who sets the duration.

The most common effect concerns blood potassium: hyperkalaemia, meaning a rise in potassium, is very common and affects at least 1 person in 10. Next come common effects, between 1 case in 100 and 1 case in 10: nausea, diarrhoea, headache and skin rash.

More serious effects exist, but they remain very rare, at fewer than 1 case in 10,000. These include blood disorders such as leukopenia, neutropenia, thrombocytopenia, agranulocytosis, megaloblastic anaemia and aplastic anaemia, as well as hyponatraemia and severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Any unexplained fever, any persistent sore throat or any widespread rash warrants prompt medical advice.

By blocking dihydrofolate reductase, trimethoprim affects an enzyme that both the bacterium and the human body use, even if the affinity for the human form remains low. In prolonged treatment, it can therefore promote megaloblastic anaemia linked to a folate deficiency. If such a deficiency appears, the physician administers calcium folinate, also known as folinic acid, which restores the folate pathway.

A monthly blood check is advised during long treatments, in people already deficient in folates and in older people. This monitoring detects a decline before it becomes problematic. Diet remains the simplest way to maintain these reserves day to day.

Several combinations call for particular vigilance. With warfarin, trimethoprim can increase the risk of bleeding. It also increases the toxicity of methotrexate and the risk of megaloblastic anaemia, raises digoxin levels, and its combination with dofetilide is contraindicated because of a risk of torsades de pointes. The risk of hyperkalaemia increases in cases of renal impairment or when combined with drugs that raise potassium, such as angiotensin-converting enzyme inhibitors.

Laboratory monitoring frames the treatment. Kidney function and serum electrolytes are monitored, particularly during prolonged use. This check makes it possible to detect hyperkalaemia or a fall in blood cell lines early, and to adjust the approach if needed. The complete list of medicines being taken should be shared with the physician and the pharmacist.