Trimethoprim and Sulfamethoxazole
Trimethoprim is available as a single drug or in combination with sulfamethoxazole (a sulfonamide antibiotic—see Sulfonamides). The drugs act synergistically to block sequential steps in bacterial folate metabolism:
This synergy results in maximal antibacterial activity, which is often bactericidal.
Trimethoprim/sulfamethoxazole (TMP/SMX) is available as a fixed combination consisting of a 1:5 ratio (80 mg TMP plus 400 mg SMX or a double-strength tablet of 160 mg TMP plus 800 mg SMX).
TMP and TMP/SMX (see Table: Some Indications for TMP/SMX) are active against
The combination is inactive against
Enterococci, many Enterobacteriaceae, and Streptococcus pneumoniae strains are resistant. TMP/SMX is not clinically effective for group A streptococcal pharyngitis.
Some Indications for TMP/SMX
TMP alone is especially useful for
TMP/SMX is in pregnancy category C (animal studies show some risk, evidence in human studies is inadequate, but clinical benefit sometimes outweighs risk). However, use near term is contraindicated; if used during pregnancy or in neonates, TMP/SMX increases blood levels of unconjugated bilirubin and increases risk of kernicterus in the fetus or neonate.
Sulfonamides enter breast milk and use during breastfeeding is usually discouraged.
Adverse effects include
Those associated with sulfonamide (see Sulfonamides : Adverse Effects)
Hyperkalemia (TMP can decrease renal tubular K excretion, leading to hyperkalemia)
Renal failure in patients with underlying renal insufficiency is probably secondary to interstitial nephritis or tubular necrosis. Also, TMP competitively inhibits renal tubular creatinine secretion and may cause an artificial increase in serum creatinine, although GFR remains unchanged. Increases in serum creatinine are more likely in patients with preexisting renal insufficiency and especially in those with diabetes mellitus.
Most adverse effects are the same as for sulfonamides. TMP has adverse effects identical to those of SMX, but they are less common. Nausea, vomiting, and rash occur most often. AIDS patients have a high incidence of adverse effects, especially fever, rash, and neutropenia.
Folate deficiency (resulting in macrocytic anemia) can also occur. Use of folinic acid can prevent or treat macrocytic anemia, leukopenia, and thrombocytopenia, which sometimes occur with prolonged TMP/SMX use.
Rarely, severe hepatic necrosis occurs. The drug may also cause a syndrome resembling aseptic meningitis.
Drug NameSelect Trade
TrimethoprimNo US brand name