Bactrim - Drug Monograph

Introduction

Bactrim is a combination antibiotic medication containing sulfamethoxazole and trimethoprim in a 5:1 ratio. This fixed-dose combination is classified as a sulfonamide antibacterial agent and is widely used for treating various bacterial infections. First approved by the FDA in 1973, Bactrim remains an important therapeutic option despite the development of newer antibiotics.

Mechanism of Action

Bactrim exerts its antibacterial effect through sequential blockade of folate metabolism. Sulfamethoxazole competitively inhibits dihydropteroate synthase, preventing the conversion of para-aminobenzoic acid (PABA) to dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, which converts dihydrofolic acid to tetrahydrofolic acid. This dual inhibition creates synergistic bactericidal activity against susceptible organisms by disrupting essential nucleic acid and protein synthesis.

Indications

FDA-approved indications include:

• Urinary tract infections
• Acute otitis media in children
• Acute exacerbations of chronic bronchitis in adults
• Traveler's diarrhea
• Pneumocystis jirovecii pneumonia (PJP) treatment and prophylaxis
• Shigellosis

Off-label uses include:

• Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections
• Toxoplasma gondii prophylaxis in immunocompromised patients
• Nocardiosis
• Stenotrophomonas maltophilia infections

Dosage and Administration

• 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours

• Renal impairment:

- CrCl 15-30 mL/min: 50% dose reduction - CrCl <15 mL/min: Not recommended

• Hepatic impairment: Use with caution, monitor liver function
• Elderly: Consider reduced dosage due to potential decreased renal function

Pharmacokinetics

Contraindications

• Hypersensitivity to sulfonamides, trimethoprim, or any component
• Documented megaloblastic anemia due to folate deficiency
• Severe hepatic impairment
• Severe renal impairment (CrCl <15 mL/min)
• Pregnancy at term and during lactation
• Infants less than 2 months of age

Warnings and Precautions

• Increased risk of death in elderly patients with serious infections
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Hematologic toxicity (thrombocytopenia, leukopenia, megaloblastic anemia)

• Monitor for hyperkalemia, particularly in elderly and those with renal impairment
• Risk of Clostridium difficile-associated diarrhea
• Photosensitivity reactions
• Hypoglycemia in patients on sulfonylureas
• Increased INR in patients on warfarin
• Folate deficiency in predisposed patients

Drug Interactions

• Warfarin: Increased anticoagulant effect
• Methotrexate: Increased toxicity risk
• Phenytoin: Increased levels
• Sulfonylureas: Enhanced hypoglycemic effect
• ACE inhibitors: Increased risk of hyperkalemia
• Cyclosporine: Increased nephrotoxicity risk

• Thiazide diuretics: Increased thrombocytopenia risk
• Procainamide: Increased levels
• Azathioprine: Increased myelosuppression risk

Adverse Effects

• Nausea/vomiting (8-10%)
• Rash (3-5%)
• Pruritus (2-3%)
• Diarrhea (2-3%)
• Anorexia (1-2%)

• Stevens-Johnson syndrome/Toxic epidermal necrolysis
• Agranulocytosis
• Aplastic anemia
• Hepatotoxicity
• Renal toxicity
• Anaphylaxis
• QT prolongation
• Aseptic meningitis

Monitoring Parameters

• Complete blood count with differential
• Renal function tests (BUN, creatinine)
• Liver function tests
• Electrolytes (particularly potassium)
• Folate levels in high-risk patients

• CBC weekly for prolonged therapy
• Renal function weekly
• Signs of hypersensitivity reactions
• Skin changes suggesting severe reactions
• Signs of bleeding or infection
• Serum potassium levels

Patient Education

• Complete full course of therapy even if feeling better
• Take with 8 oz of water to prevent crystalluria
• Maintain adequate hydration
• Avoid excessive sun exposure, use sunscreen
• Report any rash, fever, sore throat, mouth ulcers, or unusual bleeding/bruising
• Notify all healthcare providers of Bactrim use
• Do not use in pregnancy or while breastfeeding without medical advice
• Be aware of potential interactions with other medications
• Monitor for signs of diarrhea, especially if bloody or persistent

References

1. FDA Prescribing Information: Bactrim (sulfamethoxazole and trimethoprim) tablets. Revised 2022. 2. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy. 52nd edition. 2022. 3. Stevens DL, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections. Clinical Infectious Diseases. 2014;59(2):e10-e52. 4. Mandell GL, et al. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th edition. Elsevier; 2019. 5. Smilack JD. Trimethoprim-Sulfamethoxazole. Mayo Clinic Proceedings. 1999;74(7):730-734. 6. Gleckman R, et al. Sulfamethoxazole-trimethoprim. Annals of Internal Medicine. 1979;91(3):420-426. 7. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 32nd edition. 2022.