Overview
Sulfamethoxazole/trimethoprim is a fixed-dose combination antibiotic effective against susceptible bacteria. It works synergistically by inhibiting sequential steps in bacterial folate synthesis. It is commonly used for urinary tract infections, respiratory infections, shigellosis, traveler's diarrhea, and Pneumocystis jirovecii pneumonia treatment and prophylaxis.
Mechanism of Action
Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking para-aminobenzoic acid incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, preventing tetrahydrofolic acid production. This sequential dual blockade of folate synthesis produces synergistic antibacterial activity.
Indications
- Urinary tract infections due to susceptible organisms including E. coli, Klebsiella, Enterobacter, Morganella, and Proteus species
- Acute otitis media in children due to Streptococcus pneumoniae or Haemophilus influenzae
- Acute exacerbations of chronic bronchitis in adults due to S. pneumoniae or H. influenzae
- Shigellosis caused by Shigella flexneri or Shigella sonnei
- Pneumocystis jirovecii pneumonia treatment and prophylaxis in immunocompromised patients
- Traveler's diarrhea in adults due to enterotoxigenic E. coli
Common Doses
- Oral suspension: 200 mg sulfamethoxazole/40 mg trimethoprim per 5 mL
- Single strength tablets: 400 mg sulfamethoxazole/80 mg trimethoprim
- Double strength tablets: 800 mg sulfamethoxazole/160 mg trimethoprim
- Injection: 400 mg sulfamethoxazole/80 mg trimethoprim per 5 mL
Dosage
Dosage varies by indication: For urinary tract infections, adults typically take 20 mL (4 teaspoonfuls) every 12 hours for 10-14 days. Pediatric dosing is weight-based at 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours divided every 12 hours. Renal impairment requires dosage adjustment based on creatinine clearance.
Contraindications
- Known hypersensitivity to trimethoprim or sulfonamides
- History of drug-induced immune thrombocytopenia with trimethoprim/sulfonamides
- Documented megaloblastic anemia due to folate deficiency
- Pediatric patients less than 2 months of age
- Marked hepatic damage
- Severe renal insufficiency when renal function cannot be monitored
- Concomitant administration with dofetilide
Side Effects
- Common: Gastrointestinal disturbances (nausea, vomiting, anorexia), allergic skin reactions (rash, urticaria)
- Serious: Severe cutaneous adverse reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS), blood dyscrasias (agranulocytosis, aplastic anemia, thrombocytopenia), hepatic necrosis, acute lung injury, anaphylaxis, circulatory shock
- Other: Hyperkalemia, hyponatremia, renal impairment, aseptic meningitis, QT prolongation, pancreatitis
Interactions
- Dofetilide: Contraindicated due to increased dofetilide concentrations and risk of fatal arrhythmias
- Warfarin: May potentiate anticoagulant effect
- Methotrexate: Increased methotrexate toxicity risk
- Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers: Increased hyperkalemia risk
- Phenytoin: May increase phenytoin levels
- Oral hypoglycemics: Cross-sensitivity and hypoglycemia possible
Counseling Points
- Complete full course of therapy even if symptoms improve
- Take with plenty of water to prevent crystalluria
- Avoid excessive sun exposure due to photosensitivity risk
- Report any rash, fever, sore throat, unusual bleeding/bruising, or yellowing of skin/eyes immediately
- Use additional contraception if taking oral contraceptives
- Monitor for signs of diarrhea, especially if severe or bloody