Does trimethoprim‑sulfamethoxazole (Septra) provide coverage for methicillin‑resistant Staphylococcus aureus (MRSA) and Group B Streptococcus (Streptococcus agalactiae)?

Trimethoprim-Sulfamethoxazole (Septra) Coverage for MRSA and Group B Streptococcus

Septra provides excellent coverage for MRSA but should NOT be used as monotherapy for Group B Streptococcus infections due to intrinsic resistance. 1

Coverage for MRSA

Trimethoprim-sulfamethoxazole is a first-line oral antibiotic for community-acquired MRSA skin and soft tissue infections. 2, 1

Evidence Supporting MRSA Coverage

• The Infectious Diseases Society of America explicitly recommends TMP-SMX as a primary oral option for suspected or confirmed CA-MRSA in skin and soft tissue infections 2, 1
• TMP-SMX is effective against both methicillin-susceptible S. aureus (MSSA) and community-acquired MRSA strains 1
• For impetigo or ecthyma when MRSA is suspected or confirmed, TMP-SMX is specifically recommended alongside doxycycline and clindamycin 2
• After incision and drainage of skin abscesses caused by S. aureus, TMP-SMX is listed as one of the primary oral antibiotic options 1

Clinical Applications for MRSA

• Purulent skin infections: TMP-SMX is appropriate for abscesses (after drainage), furuncles, and purulent cellulitis where MRSA is suspected 1, 3
• Treatment duration: Typically 5-10 days based on clinical response 1
• Dosing: Standard adult dosing is 1-2 double-strength tablets (160/800 mg) twice daily 2

Important Limitations for MRSA Use

• Severe infections requiring hospitalization: Guidelines recommend more potent agents such as vancomycin, linezolid, or daptomycin instead of TMP-SMX 1
• Pneumonia: While some research suggests TMP-SMX may be effective for MRSA pneumonia 4, guidelines recommend vancomycin or linezolid for CA-MRSA pneumonia requiring hospitalization 2
• Resistance concerns: TMP-SMX resistance in MRSA remains relatively uncommon but can occur, particularly in institutions with high HIV patient populations due to Pneumocystis prophylaxis exposure 5

Coverage for Group B Streptococcus (Streptococcus agalactiae)

TMP-SMX does NOT reliably cover Group B Streptococcus and should never be used as monotherapy when this pathogen is suspected. 1, 6, 3

Critical Evidence Gap

• The American Academy of Pediatrics explicitly states that TMP-SMX should not be used as a single agent in the initial treatment of cellulitis because of the possibility it is caused by Group A Streptococcus (and by extension, other beta-hemolytic streptococci including Group B) and the possibility of intrinsic resistance 1
• TMP-SMX does not reliably cover beta-hemolytic streptococci, which includes Group B Streptococcus 3
• Tetracyclines (including doxycycline) similarly lack reliable activity against beta-hemolytic streptococci 6, 3

When Combination Therapy Is Required

For mixed infections potentially involving both S. aureus and streptococci, combination therapy with a β-lactam (e.g., amoxicillin or cephalexin) is mandatory. 1, 6

• Recommended combinations: TMP-SMX PLUS amoxicillin, or TMP-SMX PLUS cephalexin 1, 6
• Alternative single agent: Clindamycin alone covers both streptococci and MRSA, avoiding the need for combination therapy (but only if local MRSA clindamycin resistance is <10%) 2, 1, 6

Practical Clinical Algorithm

For Purulent Infections (Suspected MRSA)

1. Primary treatment: Incision and drainage 1
2. Add TMP-SMX monotherapy if: Severe/extensive disease, multiple sites, rapid progression, systemic illness, immunosuppression, or lack of response to drainage alone 1, 3
3. Duration: 5-10 days based on clinical response 1

For Non-Purulent Cellulitis (Possible Streptococcal Infection)

1. DO NOT use TMP-SMX alone 1, 6
2. Use either:
   • Beta-lactam monotherapy (cephalexin, dicloxacillin, amoxicillin) for typical cellulitis 6
   • TMP-SMX PLUS a beta-lactam if MRSA risk factors are present 1, 6
   • Clindamycin monotherapy (covers both) if local resistance is low 2, 1

Common Pitfalls to Avoid

• Never use TMP-SMX as monotherapy for typical cellulitis without purulent drainage, as streptococcal coverage will be inadequate 1, 6
• Do not assume TMP-SMX covers all streptococcal species—it specifically lacks reliable activity against beta-hemolytic streptococci including Group B Streptococcus 1, 3
• For severe infections requiring hospitalization, switch to IV vancomycin, linezolid, or daptomycin rather than relying on oral TMP-SMX 1