Trimethoprim-Sulfamethoxazole Dosing for MRSA Infections
For adult outpatients with MRSA skin and soft tissue infections, use TMP-SMX 1-2 double-strength tablets (160mg/800mg) twice daily for 5-10 days, with the higher dose (2 tablets twice daily) reserved for more severe infections. 1
Adult Dosing Recommendations
- Standard dose: TMP-SMX 160mg/800mg (1 double-strength tablet) twice daily is effective for uncomplicated MRSA skin infections 1, 2
- High dose: TMP-SMX 320mg/1600mg (2 double-strength tablets) twice daily can be used for more severe infections, though clinical resolution rates are similar to standard dosing 2
- Duration: 5-10 days based on clinical response 3, 1
The IDSA guidelines recommend TMP-SMX as a first-line oral option for empirical coverage of community-acquired MRSA in outpatients with skin and soft tissue infections 3. A prospective observational study found no significant difference in clinical resolution between high-dose (320/1600mg twice daily) and standard-dose (160/800mg twice daily) regimens, with resolution rates of 73% versus 75% respectively 2.
Pediatric Dosing
- Dose: 8-12 mg/kg/day based on the trimethoprim component 1
- Frequency: Divided into 2 oral doses daily or 4 IV doses daily 1
- Duration: 5-10 days based on clinical response 1
Clinical Context and Limitations
Important caveat: TMP-SMX should not be used as monotherapy for severe MRSA infections requiring hospitalization. A randomized controlled trial demonstrated that high-dose TMP-SMX (320mg/1600mg twice daily) failed to achieve non-inferiority compared to vancomycin for severe MRSA infections, particularly in bacteremic patients where mortality was 34% with TMP-SMX versus 18% with vancomycin 4.
For hospitalized patients with complicated skin and soft tissue infections, IV vancomycin, linezolid, daptomycin, or telavancin should be used instead 3.
When TMP-SMX is Appropriate
TMP-SMX is recommended for:
- Purulent cellulitis in outpatients (cellulitis with purulent drainage but no drainable abscess) 3
- Abscesses requiring antibiotics after incision and drainage, particularly with severe/extensive disease, systemic symptoms, immunosuppression, or difficult-to-drain locations 3, 1
- Nonpurulent cellulitis that fails beta-lactam therapy, combined with a beta-lactam for streptococcal coverage 3
Combination Therapy Considerations
If coverage for both beta-hemolytic streptococci and MRSA is needed, combine TMP-SMX with a beta-lactam such as amoxicillin, as TMP-SMX lacks reliable streptococcal activity 3.