What are the recommended indications, dosing, contraindications, renal dose adjustments, and alternative therapies for Bactrim (trimethoprim‑sulfamethoxazole) in adult patients?

Bactrim (Trimethoprim-Sulfamethoxazole) Clinical Recommendations

Bactrim is a highly effective antimicrobial for specific indications including MRSA skin infections, urinary tract infections, PCP prophylaxis, and certain respiratory infections, with standard dosing of 1-2 double-strength tablets twice daily for most infections, but requires careful attention to renal dosing, contraindications in pregnancy, and monitoring for acute kidney injury in high-risk patients. 1, 2

Primary Indications

Skin and Soft Tissue Infections

• MRSA purulent cellulitis: 1-2 double-strength (DS) tablets (160/800 mg) twice daily for 7 days 1, 3
• Critical limitation: Do NOT use as monotherapy for non-purulent cellulitis—Bactrim has poor activity against beta-hemolytic streptococci and requires combination therapy for mixed aerobic-anaerobic infections 1

Urinary Tract Infections

• Acute uncomplicated UTI: 1 DS tablet every 12 hours for 10-14 days 2
• Avoid in patients with: Recent TMP-SMX use within 90 days (8.77-fold increased resistance risk), recurrent UTIs (2.27-fold increased risk), or genitourinary abnormalities (2.31-fold increased risk) 4
• Alternative consideration: Single-dose therapy (2 DS tablets once) showed 93% cure rates in research but is not FDA-approved 5

Respiratory Infections

• Acute exacerbations of chronic bronchitis: 1 DS tablet every 12 hours for 14 days 2
• Acute sinusitis (adults): Alternative to amoxicillin when first-line therapy fails, though resistance is increasing in children 6

Pneumocystis Jirovecii Pneumonia (PCP)

Treatment dosing:

• 75-100 mg/kg/day sulfamethoxazole + 15-20 mg/kg/day trimethoprim, divided every 6 hours for 14-21 days 2
• For a 70 kg adult: 2 DS tablets every 6 hours (upper limit dosing) 2

Prophylaxis dosing:

• Primary regimen: 1 DS tablet daily 6, 2
• Alternative regimen: 1 DS tablet three times weekly on consecutive days (equivalent protection, fewer side effects) 1, 3
• Initiate when: CD4+ count <200 cells/µL, or with HIV-related thrush/unexplained fevers regardless of CD4+ count, or after any prior PCP episode 6

Other Indications

• Shigellosis: 1 DS tablet every 12 hours for 5 days 2
• Traveler's diarrhea: 1 DS tablet every 12 hours for 5 days 2

Renal Dose Adjustments

Mandatory dose reduction based on creatinine clearance: 2

• CrCl >30 mL/min: Standard dosing
• CrCl 15-30 mL/min: Reduce dose by 50%
• CrCl <15 mL/min: Use NOT recommended

Hemodialysis patients requiring prophylaxis: 500 mg three times weekly after dialysis 3

Severe Infections Requiring IV Administration

IV dosing: 8-12 mg/kg/day (based on trimethoprim component) divided into 4 doses, each infused over 1 hour 1

Indications for IV route:

• Severe bacteremia, pyelonephritis, CNS infections (5 mg/kg/dose every 8-12 hours for MRSA CNS infections) 1
• Hospitalized patients unable to tolerate oral therapy 1

Transition to oral therapy: Switch when acute symptoms resolve, using the same total daily dose, only in patients with mild-to-moderate disease without malabsorption or diarrhea 1

Absolute Contraindications

• Third trimester pregnancy: Risk of kernicterus in the newborn 1, 3
• Nursing mothers: Drug excreted in breast milk 1
• Sulfa allergies: Documented hypersensitivity reactions 1
• G6PD deficiency: Risk of hemolytic anemia 3
• Infants <2 months of age: Not recommended 2

Critical Drug Interactions

• Methotrexate at treatment doses: Avoid concurrent use due to severe bone marrow suppression risk (prophylactic methotrexate doses generally tolerated) 3
• Warfarin: Monitor INR closely due to potentiation of anticoagulant effect 7

Monitoring Requirements

• Baseline and monthly hemogram: Monitor for thrombocytopenia and other hematological toxicity 3
• Renal function: Acute kidney injury (AKI) occurs in 11.2% of patients treated ≥6 days, with 5.8% likely attributable to Bactrim 8
• Highest AKI risk: Patients with poorly controlled hypertension and diabetes mellitus 8
• AKI presentation: Typically intrinsic renal impairment (not interstitial nephritis), resolves promptly after discontinuation, pyuria rare 8

Alternative Therapies by Indication

For MRSA Skin Infections

• Doxycycline 100 mg twice daily
• Clindamycin 300-450 mg three times daily (if local resistance <10%)
• Linezolid 600 mg twice daily (for severe infections)

For Urinary Tract Infections

• Nitrofurantoin 100 mg twice daily for 5-7 days (avoid if CrCl <30 mL/min)
• Fosfomycin 3 g single dose
• Fluoroquinolones (ciprofloxacin 250-500 mg twice daily) if local resistance <20%

For PCP Prophylaxis in Sulfa-Allergic Patients

• Dapsone 100 mg daily (check G6PD first)
• Atovaquone 1500 mg daily
• Aerosolized pentamidine 300 mg monthly via Respigard II nebulizer 6

For Respiratory Infections

• High-dose amoxicillin-clavulanate (2 g every 12 hours) for sinusitis 6
• Cefuroxime, cefpodoxime, or respiratory fluoroquinolones for bronchitis 6

Prophylaxis for Immunocompromised Patients

Beyond PCP, consider for:

• Bacterial respiratory tract infections in primary immunodeficiency: 160 mg trimethoprim daily or twice daily 6
• Prolonged courses (continue 7 days after clinical resolution) for adequate pathogen eradication in immunocompromised hosts 6

Common Pitfalls to Avoid

1. Do not use for non-purulent cellulitis alone—lacks streptococcal coverage 1
2. Do not ignore local resistance patterns—avoid if institutional E. coli resistance >20% for empiric UTI treatment 4
3. Do not forget renal dose adjustment—failure to reduce dose with CrCl 15-30 mL/min increases toxicity risk 2
4. Do not overlook pregnancy status—absolutely contraindicated in third trimester 1, 3
5. Do not use irradiated blood products without checking—patients with severe T-cell deficiency require CMV-negative, irradiated products if receiving Bactrim for immunodeficiency-related prophylaxis 6