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Co-trimoxazole

Moxifloxacin is a potent fluoroquinolone for respiratory, skin, and intra-abdominal infections. While effective, its use requires vigilance for QT prolongation, tendon injury, and drug interactions. Adherence to guidelines from the BNFLippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology ensures safe and effective therapy.

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 bacteriaStreptococcus pneumoniaeStaphylococcus aureus.
  • Gram-negative bacteriaEscherichia coliKlebsiellaProteusSalmonellaShigella.
  • Opportunistic pathogensPneumocystis jiroveciiToxoplasma 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. coliShigella).
    • 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. PregnancyCategory 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

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