Bactrim (Trimethoprim-Sulfamethoxazole): Clinical Guide
Primary Indications
Bactrim is FDA-approved for urinary tract infections, acute otitis media in children, shigellosis, acute exacerbations of chronic bronchitis, and Pneumocystis jirovecii pneumonia (PCP) treatment and prophylaxis. 1 Off-label uses include MRSA skin and soft tissue infections, osteomyelitis, and opportunistic infection prophylaxis in immunocompromised patients. 2, 3
Adult Dosing Regimens
Standard Infections
- Urinary tract infections and shigellosis: 1 double-strength (DS) tablet (160 mg TMP/800 mg SMX) every 12 hours for 10-14 days (UTI) or 5 days (shigellosis). 1
- Acute exacerbations of chronic bronchitis: 1 DS tablet every 12 hours for 14 days. 1
- MRSA skin and soft tissue infections: 1-2 DS tablets twice daily for 7-10 days, using the higher dose (2 DS tablets) for severe infections. 2, 3 Note that Bactrim has poor activity against beta-hemolytic streptococci and should not be used as monotherapy for non-purulent cellulitis. 2
Severe/Life-Threatening Infections
- IV administration for severe infections: 8-12 mg/kg/day (based on trimethoprim component) divided into 4 doses, each infused over 1 hour. 2
- MRSA CNS infections (meningitis, brain abscess): 5 mg/kg/dose (trimethoprim) IV every 8-12 hours. 3
- MRSA osteomyelitis: 3.5-4.0 mg/kg/dose (trimethoprim) every 8-12 hours, typically combined with rifampin for >6 weeks. 3
PCP Treatment
- Documented PCP: 75-100 mg/kg sulfamethoxazole and 15-20 mg/kg trimethoprim per 24 hours, divided every 6 hours for 14-21 days. 1 For an 80 kg adult, this translates to 2 DS tablets every 6 hours (upper limit dosing). 1
PCP Prophylaxis
- Primary prophylaxis (CD4+ <200 cells/mm³ or oropharyngeal candidiasis): 1 DS tablet daily is the preferred regimen. 4 Alternative effective regimens include 1 single-strength (SS) tablet daily or 1 DS tablet three times weekly on consecutive days. 4, 3
Pediatric Dosing (>2 Months of Age)
Standard Infections
- Most infections: 8-12 mg/kg/day trimethoprim (40-60 mg/kg/day sulfamethoxazole) divided every 12 hours. 3, 5, 1
- UTI and acute otitis media: 40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim per 24 hours, divided every 12 hours for 10 days. 1
- Shigellosis: Same as UTI dosing but for 5 days. 1
Weight-Based Dosing Table (Standard Infections)
| Weight | Dose every 12 hours |
|---|---|
| 10 kg (22 lbs) | 1 SS tablet |
| 20 kg (44 lbs) | 1 SS tablet |
| 30 kg (66 lbs) | 1½ SS tablets |
| 40 kg (88 lbs) | 2 SS tablets or 1 DS tablet |
| [1] |
Severe Infections
- Severe MRSA infections: 10-12 mg/kg/day trimethoprim, or up to 15-20 mg/kg/day divided every 6-8 hours for life-threatening infections. 3
- PCP treatment: 75-100 mg/kg sulfamethoxazole and 15-20 mg/kg trimethoprim per 24 hours, divided every 6 hours for 14-21 days. 1
PCP Prophylaxis (Pediatric)
- HIV-exposed/infected children: 150 mg/m²/day trimethoprim with 750 mg/m²/day sulfamethoxazole, divided twice daily, given 3 consecutive days per week (maximum 320 mg TMP/1600 mg SMX daily). 3, 5
Renal Dose Adjustments
Dose reduction is mandatory when creatinine clearance falls below 30 mL/min to prevent severe toxicity. 3
Treatment Dosing
- CrCl 15-30 mL/min: Reduce dose by 50% (use half the usual regimen). 3, 1
- CrCl 10-50 mL/min (PCP treatment): 3-5 mg/kg trimethoprim every 12 hours instead of every 6-8 hours. 3
- CrCl <10 mL/min (PCP treatment): 3-5 mg/kg trimethoprim every 24 hours. 3
- CrCl <15 mL/min: FDA label advises against use, though clinical guidelines support reduced dosing or alternative agents. 3, 1
Prophylaxis Dosing
- CrCl 15-30 mL/min: Reduce prophylactic dose by 50%. 3
- CrCl <15 mL/min: Reduce by 50% or use alternative agent. 3
IV to Oral Transition
- Criteria for safe conversion: Patients with mild-to-moderate disease who do not have malabsorption or diarrhea may transition from IV to oral using the same total daily dose. 2
- Post-acute pneumonitis: After clinical resolution, switch to oral therapy to complete the prescribed course. 2
Critical Contraindications
- Age <2 months: Absolute contraindication due to kernicterus risk. 5, 1
- Third trimester pregnancy: Contraindicated due to kernicterus risk in the newborn. 2
- Nursing mothers: Contraindicated. 2
- Sulfa allergy: Avoid in patients with documented hypersensitivity to sulfonamides or trimethoprim. 2, 5
- Severe hepatic impairment: Should be avoided. 3
Monitoring Requirements
Hematologic Monitoring
- Baseline: Obtain complete blood count with differential and platelet count at treatment initiation. 3, 5
- Prolonged therapy: Repeat CBC monthly to assess for neutropenia, thrombocytopenia, and anemia. 3, 5
- G6PD deficiency screening: Screen before initiating therapy due to hemolytic anemia risk. 3, 5
Renal and Metabolic Monitoring
- High-dose therapy: Regularly assess creatinine clearance and electrolytes to detect drug accumulation and toxicity. 3
- Hydration: Ensure at least 1.5 liters of fluid daily to prevent crystalluria, especially during high-dose therapy. 3
Important Drug Interactions
- Methotrexate: Bactrim may increase methotrexate toxicity; use with extreme caution. 3, 5
- Warfarin and anticoagulants: Enhanced anticoagulant effect; monitor INR closely. 3, 5
- Oral hypoglycemics: Increased risk of hypoglycemia; monitor blood glucose. 3, 5
- Thiazide diuretics and anticonvulsants: Potential for increased adverse effects. 5
Adverse Effects and Management
Common Reactions (≈15% in HIV-infected patients)
- Dermatologic: Rash is most common. For mild rash, temporarily discontinue and restart when resolved. For urticarial rash or Stevens-Johnson syndrome, permanently discontinue. 5
- Hematologic: Neutropenia, thrombocytopenia, anemia. 5
- Gastrointestinal: Nausea, vomiting, diarrhea. 5
- Hepatic: Hepatitis. 5
- Renal: Interstitial nephritis. 5
Desensitization for Non-Life-Threatening Reactions
- If a patient experienced a non-life-threatening adverse reaction (especially fever and rash), gradual dose escalation (desensitization) or reintroduction at reduced dosage may allow up to 70% of patients to tolerate therapy. 4
Special Populations
Immunocompromised Patients
- Severely immunocompromised (CD4+ <200): Use 1 DS tablet daily for PCP prophylaxis. 4
- Toxoplasma-seropositive patients intolerant to TMP-SMZ: Consider dapsone plus pyrimethamine or atovaquone with/without pyrimethamine for dual PCP and toxoplasmosis prophylaxis. 4