Co-trimoxazole is a fixed-dose combination of two antimicrobial agents: sulfamethoxazole (a sulfonamide) and trimethoprim (a diaminopyrimidine). The combination works synergistically to inhibit sequential steps in bacterial folate synthesis:

1. Sulfamethoxazole: Inhibits dihydropteroate synthase, blocking the conversion of PABA to dihydrofolic acid.
2. Trimethoprim: Inhibits dihydrofolate reductase, preventing the conversion of dihydrofolic acid to tetrahydrofolic acid.
   This dual action disrupts DNA, RNA, and protein synthesis, leading to bacteriostatic effects.

Co-trimoxazole is effective against:

• Gram-positive bacteria: Streptococcus pneumoniae, Staphylococcus aureus.
• Gram-negative bacteria: Escherichia coli, Klebsiella, Proteus, Salmonella, Shigella.
• Opportunistic pathogens: Pneumocystis jirovecii, Toxoplasma gondii.

Co-trimoxazole is indicated for:

1. Respiratory Infections:
   • Acute exacerbations of chronic bronchitis.
   • Community-acquired pneumonia (especially Pneumocystis jirovecii pneumonia in immunocompromised patients).
2. Urinary Tract Infections (UTIs):
   • Acute uncomplicated cystitis.
   • Recurrent UTIs.
3. Gastrointestinal Infections:
   • Traveler’s diarrhea (E. coli, Shigella).
   • Typhoid fever (Salmonella typhi).
4. Opportunistic Infections:
   • Pneumocystis pneumonia (PCP): Prophylaxis and treatment in HIV/AIDS patients.
   • Toxoplasmosis: Prophylaxis in immunocompromised patients.
5. Skin and Soft Tissue Infections:
   • Cellulitis, wound infections.

Adults:

• Standard Dose: 960 mg (sulfamethoxazole 800 mg + trimethoprim 160 mg) twice daily.
• PCP Treatment: 120 mg/kg/day in divided doses for 14–21 days.
• PCP Prophylaxis: 960 mg once daily or 3 times weekly.

Children:

• Standard Dose: 24 mg/kg/day (sulfamethoxazole 20 mg/kg + trimethoprim 4 mg/kg) in divided doses.
• PCP Prophylaxis: 450 mg/m² twice daily on 3 consecutive days per week.

Special Populations:

• Renal Impairment: Adjust dose based on creatinine clearance (CrCl):
  • CrCl 15–30 mL/min: Reduce dose by 50%.
  • CrCl <15 mL/min: Avoid unless essential.

Hepatic Impairment: Use with caution; monitor LFTs.

• Common: Nausea, vomiting, diarrhea, rash, headache.
• Serious:
  • Hematologic Effects: Megaloblastic anemia, leukopenia, thrombocytopenia.
  • Hypersensitivity Reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis.
  • Renal Toxicity: Crystalluria, interstitial nephritis.
  • Hyperkalemia: Due to trimethoprim’s potassium-sparing effect.
  • Hepatotoxicity: Elevated LFTs, hepatitis.

1. Hypersensitivity: Avoid in patients with sulfonamide allergy.
2. Pregnancy: Category C (avoid in third trimester due to risk of kernicterus).
3. Lactation: Excreted in breast milk; avoid breastfeeding.
4. Renal/Hepatic Impairment: Monitor renal function and LFTs.
5. Folate Deficiency: Supplement with folic acid in high-risk patients (e.g., elderly, malnourished).

Co-trimoxazole interacts with drugs metabolized by CYP450 enzymes and those affecting folate metabolism:

• Warfarin: Increased INR (monitor closely).
• Phenytoin: Increased levels (risk of toxicity).
• Methotrexate: Increased toxicity (avoid combination).
• ACE Inhibitors: Increased risk of hyperkalemia.
• Cyclosporine: Increased nephrotoxicity.
• Oral Hypoglycemics: Enhanced hypoglycemic effect.

• Generic: Co-trimoxazole (sulfamethoxazole + trimethoprim).

Brand Names: Bactrim, Septra, Septrin