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# Co-trimoxazole (Septra, Bactrim)
## Overview
Co-trimoxazole is a combination antibiotic agent containing trimethoprim and sulfamethoxazole in a fixed ratio (1:5). It inhibits sequential steps in the folic acid synthesis pathway in bacteria, leading to bacterial cell death.
## Primary Indications
* Urinary tract infections (uncomplicated cystitis, prostatitis)
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* *Shigella* gastroenteritis
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* *Staphylococcus aureus* skin infections (including MRSA in some cases)
## Adult Dosing
Dosing is typically based on the trimethoprim component.
* **Urinary Tract Infections:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days (cystitis) or 14 days (prostatitis).
* **PCP Treatment:** 15 mg/kg/day trimethoprim equivalent, divided every 6 hours for 14-21 days. Usual dose: 15 mg/kg/day in 4 divided doses.
* **PCP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily or 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) three times weekly.
* **Other Infections:** Varies based on indication and severity; consult specific guidelines.
## Pediatric Dosing
Dosing is typically based on the trimethoprim component and patient weight.
* **General Infections:** 8 mg/kg/day trimethoprim equivalent, divided every 12 hours.
* **PCP Treatment:** 15 mg/kg/day trimethoprim equivalent, divided every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 75 mg/m²/day trimethoprim equivalent, divided every 12 hours, on 3 consecutive days per week.
**Note:** The "DS" (double strength) tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole. Pediatric dosing may require use of oral suspension or breaking tablets, depending on formulation and age.
## Dose Adjustments
* **Renal Impairment (CrCl > 30 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 25-50%.
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use.
* **Hepatic Impairment:** Use with caution; no specific dosing guidelines.
## Contraindications
* Hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* Megaloblastic anemia due to folate deficiency.
* Infants < 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
## Adverse Effects
Common: Rash, pruritus, nausea, vomiting, diarrhea.
Serious:
* **Hypersensitivity:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fixed drug eruption, anaphylaxis.
* **Hematologic:** Agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia, leukopenia.
* **Renal:** Acute interstitial nephritis, crystalluria (especially with inadequate fluid intake).
* **Hepatic:** Hepatitis, cholestatic jaundice.
* **Other:** Hyperkalemia, hyponatremia, photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR; monitor INR closely.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of bone marrow suppression.
* **Diuretics (especially thiazides in elderly):** Increased risk of thrombocytopenia.
* **Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Dapsone:** Increased risk of methemoglobinemia.
## Monitoring
* **Renal function:** Baseline and during therapy, especially in patients with pre-existing renal disease or receiving concomitant nephrotoxic agents.
* **Complete blood count (CBC) with differential:** Baseline and periodically during prolonged therapy or in immunocompromised patients. Discontinue if significant reduction in WBCs, platelets, or Hb.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or taking other agents that affect potassium.
* **Hydration:** Encourage adequate fluid intake to prevent crystalluria.
* **Signs of hypersensitivity:** Monitor closely for rash, fever, and mucosal lesions.
## Clinical Pearls
* Fluid intake should be adequate to prevent crystalluria and sulfonamide precipitation in the renal tubules.
* Co-trimoxazole can cause a false-positive urine glucose test.
* The risk of SJS/TEN is higher in patients with HIV/AIDS.
* Therapy duration should be appropriate for the infection being treated; prolonged use increases the risk of adverse effects.
* Local resistance patterns should be considered when choosing antibiotic therapy.
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*Disclaimer: This information is intended for healthcare professionals and does not replace professional judgment. Always consult the most current prescribing information and relevant clinical guidelines for definitive patient care decisions.*
