Generic Name

Bactrim

Mechanism

Bactrim is a fixed‑ratio combination of *trimethoprim* (TMP) and *sulfamethoxazole* (SMX).
• Trimethoprim selectively inhibits bacterial dihydrofolate reductase (DHFR), blocking the conversion of dihydrofolate to tetrahydrofolate.
• Sulfamethoxazole is a structural analog of para‑aminobenzoic acid (PABA) and competitively inhibits dihydropteroate synthase (DHPS) in the folate synthesis pathway.

The dual blockade creates a synergistic interruption of bacterial folate metabolism, reducing production of nucleic acids and proteins.

Pharmacokinetics

• Absorption: Oral bioavailability ~50–70 % (TMP higher). Rapidly absorbed; peak plasma levels within 1–2 h (SMX ~3–4 h).
• Distribution: Widely distributed; penetrates the CNS, urethra, prostate, and most body fluids. TMP binds ~50 % to plasma proteins; SMX ~9 %.
• Metabolism: Primarily hepatic via glucuronidation (TMP) and oxidation (SMX).
• Elimination: Renal excretion 70–80 % as unchanged drug (both compounds).
• Half‑life: TMP ~6–8 h; SMX ~7–10 h (shortened with renal impairment).

Indications

• Uncomplicated *urinary tract infections* (UTIs).
• *Prophylaxis and treatment* of *Pneumocystis jirovecii* pneumonia (PCP).
• Respiratory infections: bacterial sinusitis, community‑acquired pneumonia (with β‑lactam cover).
• Gastrointestinal infections: *Campylobacter*, *Shigella*, *Salmonella*, *Clostridium difficile* (initial or relapse).
• Skin and soft‑tissue infections caused by susceptible organisms.
• *Immunocompromised hosts* for other opportunistic infections (e.g., *Bacillus anthracis* post‑exposure).

Contraindications

• Allergy to sulfonamides or trimethoprim.
• G6PD deficiency (risk of hemolysis).
• Severe renal or hepatic impairment without dose adjustment.
• Pregnancy: 3rd trimester (risk of neonatal jaundice, bilirubin diathesis).
• Pediatric use < 2 weeks (high risk of kernicterus).
• Prolonged therapy in patients with chronic kidney disease (monitor renal function).

Dosing

• Adjust dose based on creatinine clearance (≥ 50 mL/min: unchanged; 30–49 mL/min: 50 %; < 30 mL/min: 25 %).
• Oral suspension: 2 mL per unit (80 mg/400 mg).
• IV formulation: 4 g vials (TMP 80 mg; SMX 400 mg), diluted in 250 mL IV fluid, administered over 30 min.

Adverse Effects

Common
• Gastrointestinal: nausea, vomiting, dyspepsia, diarrhea.
• Rash: maculopapular.
• Hematologic: mild leukopenia or thrombocytopenia.
• Hepatic enzyme elevations (transaminases 2–3 × ULN).

Serious
• Bone‑marrow suppression: agranulocytosis, aplastic anemia.
• Severe cutaneous reactions: Stevens–Johnson syndrome, toxic epidermal necrolysis.
• Renal crystal nephropathy: flank pain, hematuria.
• Hyperkalemia: especially in renal impairment.
• Hypersensitivity reactions: anaphylaxis, angioedema.

Monitoring

• Baseline & periodic CBC (with differential) every 1–2 weeks for prolonged courses.
• Serum creatinine & BUN: at baseline and twice weekly if CrCl < 50 mL/min; weekly thereafter.
• Liver function tests (ALT/AST, bilirubin): baseline; repeat at 2–4 weeks for long‑term therapy.
• Serum electrolytes: monitor for hyperkalemia in renal impairment.
• Urinalysis: for crystal formation or hematuria.

Clinical Pearls

• Trimethoprim–sulfamethoxazole acts synergistically; monotherapy with either agent is ineffective due to rapid resistance development.
• The 80/400 mg ratio (TMP:SMX) maximizes antimicrobial activity while minimizing toxicity.
• High-dose Bactrim (15/75 mg/kg) for PCP overwhelms the pathogen’s folate pathway; ensure IV access when CrCl < 30 mL/min to avoid renal dose accumulation.
• Avoid Bactrim in patients with G6PD deficiency; even low doses can precipitate hemolysis.
• Sulfamethoxazole crystals form more readily in acidic urine; advise adequate hydration and consider alkalinizing agents in high‑dose or renal‑impaired patients.
• In pediatric patients, weight‑based dosing (TMP 5–10 mg/kg, SMX 20–25 mg/kg) reduces the risk of kernicterus; monitor CBC and renal function.
• Pregnancy: First two trimesters may be acceptable with caution; third trimester avoidance recommended unless the benefit outweighs risks (e.g., severe PCP).
• For PCP prophylaxis, the same dosing (80/400 mg BID) as for uncomplicated UTI suffices; discontinue after immune reconstitution or 6 months after last dose of immunosuppressive therapy.

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• This concise Bactrim drug card balances depth and clarity, perfect for quick reference by medical students and clinicians alike.