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# Co-Trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic comprising trimethoprim and sulfamethoxazole in a fixed ratio of 1:5. It inhibits bacterial folic acid synthesis. Available as oral tablets (e.g., 80 mg TMP/400 mg SMX, 160 mg TMP/800 mg SMX) and intravenous infusion.
## Primary Indications
* Urinary tract infections (UTIs)
* *Pneumocystis jirovecii* pneumonia (PCP) prophylaxis and treatment
* Certain respiratory tract infections (e.g., acute exacerbations of chronic bronchitis)
* *Shigella* gastroenteritis
* *Staphylococcus aureus* skin and soft tissue infections (including MRSA in some cases)
* Prophylaxis against *Pneumocystis jirovecii* pneumonia in immunocompromised individuals.
## Adult Dosing
Dosing is typically based on the trimethoprim component. Standard adult dose: 160 mg TMP (1 DS tablet) PO or IV every 12 hours.
* **UTIs:** 160 mg TMP (1 DS tablet) PO every 12 hours for 3-7 days.
* **PCP Treatment:** 15-20 mg TMP/kg/day PO or IV divided into 3-4 doses for 14-21 days.
* **PCP Prophylaxis:** 160 mg TMP (1 DS tablet) PO once daily, or 160 mg TMP (1 DS tablet) PO 3 times per week (alternative schedule).
* **MRSA Skin/Soft Tissue Infections:** Dosing varies, often higher doses may be considered. Consult local guidelines.
## Pediatric Dosing
Dosing is based on the trimethoprim component and patient weight.
* **General Infections:** 8-10 mg TMP/kg/day PO or IV divided into 2 doses.
* **PCP Treatment:** 15-20 mg TMP/kg/day PO or IV divided into 3-4 doses for 14-21 days.
* **PCP Prophylaxis:** 5 mg TMP/kg/day PO divided into 2 doses, or 10 mg TMP/kg once daily, 3 days per week (alternative schedule).
* **Infants < 2 months:** Generally *avoided* due to risk of kernicterus.
## Dose Adjustments
* **Renal Impairment (CrCl):**
* CrCl > 30 mL/min: Standard dose.
* CrCl 15-30 mL/min: Administer 75% of standard dose.
* CrCl < 15 mL/min: Administer 50% of standard dose or administer every 24 hours. Consider dialysis dosing.
## Contraindications
* Documented hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Megaloblastic anemia due to folate deficiency.
* Severe renal insufficiency when frequent monitoring of plasma concentrations is impossible.
* Infants < 2 months of age.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea, hyperkalemia.
Serious: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), severe dermatologic reactions, bone marrow suppression (anemia, leukopenia, thrombocytopenia), hepatitis, renal failure, hyperkalemia, hyponatremia.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE inhibitors/ARBs/Potassium-sparing diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased methotrexate levels and toxicity.
* **Potassium supplements/Potassium-containing salt substitutes:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Dofetilide:** Increased risk of dofetilide-induced arrhythmias.
* **Certain oral hypoglycemics:** May potentiate effects.
## Monitoring
* Renal function (BUN, creatinine).
* Complete blood count (CBC) with differential, particularly with prolonged therapy or in immunocompromised patients.
* Electrolytes (especially potassium and sodium).
* Liver function tests.
* Therapeutic drug monitoring of trimethoprim and sulfamethoxazole levels may be indicated in certain situations (e.g., PCP treatment, renal impairment).
## Clinical Pearls
* Adequate fluid intake is crucial to prevent crystalluria.
* Sulfonamides can displace bilirubin from albumin; use with caution in jaundiced neonates and patients with hyperbilirubinemia.
* Concurrent folic acid supplementation (e.g., 5 mg daily) may be considered in patients on prolonged therapy to reduce risk of hematologic side effects, particularly in HIV-positive individuals, but may potentially reduce efficacy in PCP treatment.
* IV co-trimoxazole must be diluted and infused slowly to prevent infusion reactions.
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*This information is intended for healthcare professionals and is not exhaustive. Always consult the most current prescribing information, institutional protocols, and relevant literature before making clinical decisions.*
