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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic containing trimethoprim and sulfamethoxazole in a synergistic ratio, typically 1:5. It exhibits broad-spectrum activity against many gram-positive and gram-negative bacteria.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Certain bacterial respiratory tract infections
* Certain bacterial gastrointestinal infections
## Adult Dosing
Dosing is based on the trimethoprim component, with standard dose typically representing 160 mg trimethoprim/800 mg sulfamethoxazole.
* **UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours for 3-7 days.
* **PJP Treatment:** 160 mg trimethoprim/800 mg sulfamethoxazole every 6 hours for 14-21 days.
* **PJP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole once daily, or 80 mg trimethoprim/400 mg sulfamethoxazole twice daily, or 160 mg trimethoprim/800 mg sulfamethoxazole three times weekly.
* **Other Infections:** Dosing varies by severity and indication. A common regimen is 160 mg trimethoprim/800 mg sulfamethoxazole every 12 hours.
Maximum dose: Generally 320 mg trimethoprim/1600 mg sulfamethoxazole per day, but may be higher for PJP treatment.
## Pediatric Dosing
Dosing is based on the trimethoprim component, usually calculated as mg/kg/day divided into two or three doses.
* **General Infections:** 8 mg trimethoprim/kg/day divided every 12 hours.
* **PJP Treatment:** 15 mg trimethoprim/kg/day divided every 6 hours.
* **PJP Prophylaxis:** 5 mg trimethoprim/kg/day given once daily, or 7.5 mg trimethoprim/kg/day given three times weekly.
Maximum pediatric doses typically align with adult maximums. Specific dosing may depend on local pediatric protocols.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is required based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: No adjustment.
* CrCl 15-30 mL/min: Reduce dose by 50%.
* CrCl < 15 mL/min: Avoid use or use with extreme caution and monitor closely.
## Contraindications
* Hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic impairment.
* Patients with porphyria.
## Adverse Effects
Common adverse effects include rash, nausea, vomiting, and diarrhea. Serious adverse effects include:
* Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
* Hematologic abnormalities (anemia, leukopenia, thrombocytopenia, agranulocytosis)
* Hyperkalemia
* Hepatitis, cholestatic jaundice
* Renal dysfunction
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity; trimethoprim can inhibit dihydrofolate reductase.
* **Procainamide/Amantadine:** Increased plasma concentrations.
* **Sulfonylureas/Dapson/Phenytoin:** Increased risk of hypoglycemia or toxicity.
## Monitoring
* **Renal function:** Especially in patients with pre-existing renal impairment.
* **Complete blood counts (CBC):** Periodically, especially with prolonged therapy or in immunocompromised patients.
* **Electrolytes:** Particularly potassium levels.
* **Liver function tests:** Periodically.
* **Signs of hypersensitivity:** Skin rash, fever.
## Clinical Pearls
* Administer oral formulations with food or milk to minimize gastrointestinal upset.
* Ensure adequate hydration to prevent crystalluria.
* Co-trimoxazole is teratogenic, especially in the first trimester (folate antagonist activity). Avoid use in pregnancy unless benefits outweigh risks.
* In patients with G6PD deficiency, sulfonamides can precipitate hemolytic anemia.
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**Disclaimer:** This information is intended for clinical decision support and is not a substitute for professional medical judgment. Always consult the most current prescribing information, institutional protocols, and drug databases for complete and up-to-date details.
