Is Staphylococcus aureus (Staph aureus) covered by Bactrim (trimethoprim/sulfamethoxazole)?

Yes, Bactrim (trimethoprim-sulfamethoxazole) provides effective coverage against Staphylococcus aureus, including both methicillin-susceptible (MSSA) and community-acquired methicillin-resistant strains (CA-MRSA).

Coverage Spectrum

Bactrim is recommended as a first-line oral treatment option for skin and soft tissue infections caused by both MSSA and CA-MRSA 1. The Infectious Diseases Society of America (IDSA) specifically lists TMP-SMX as a recommended empirical treatment for CA-MRSA in outpatients with skin and soft tissue infections 2, 1.

• Most community-acquired MRSA strains remain susceptible to trimethoprim-sulfamethoxazole 2
• For simple abscesses or boils caused by S. aureus, Bactrim is a first-line antibiotic option after incision and drainage 2, 1
• When MRSA is suspected or confirmed in impetigo or ecthyma, Bactrim is among the recommended oral agents 2

Critical Limitations and When NOT to Use Bactrim

Bactrim should NOT be used as monotherapy for cellulitis or non-purulent skin infections because it lacks reliable activity against Group A Streptococcus (Streptococcus pyogenes), which may be the causative pathogen 1. This is a common pitfall in clinical practice.

• For non-purulent cellulitis, combine Bactrim with a β-lactam (such as amoxicillin) if both streptococcal and S. aureus coverage is needed 1
• For severe S. aureus infections requiring hospitalization, use vancomycin, linezolid, or daptomycin instead of Bactrim 2, 1
• After initial clinical response in hospitalized patients, step-down to Bactrim may be possible based on susceptibility testing 2

Resistance Considerations

While most CA-MRSA remains susceptible, resistance patterns vary geographically and by patient population 3:

• Treatment failure rates of 21% have been reported with TMP-SMX in some series 2
• Resistance is particularly high in institutions serving large numbers of HIV-infected patients due to increased exposure for Pneumocystis prophylaxis 3
• In sub-Saharan Africa, 54% of S. aureus isolates showed trimethoprim resistance, predominantly mediated by the dfrG gene 4
• When prescribing Bactrim empirically, reevaluate patients in 24-48 hours to verify clinical response 2

Clinical Dosing and Duration

For uncomplicated skin and soft tissue infections caused by S. aureus 1, 5:

• Standard dose: 160 mg/800 mg (one double-strength tablet) twice daily
• High dose: 320 mg/1,600 mg (two double-strength tablets) twice daily
• Duration: 5-10 days based on clinical response 1
• A study found no difference in clinical resolution between standard and high-dose regimens (75% vs 73% cure rates) 5

Comparative Efficacy Data

In a randomized trial comparing Bactrim to vancomycin for serious S. aureus infections in intravenous drug users 6:

• Vancomycin achieved 98% cure rate versus 86% for Bactrim (p<0.02) 6
• All treatment failures with Bactrim occurred in patients with MSSA infection, particularly tricuspid valve endocarditis 6
• This suggests Bactrim may be considered as an alternative for selected cases of MRSA infection, but vancomycin remains superior for severe infections 6

Clinical Decision Algorithm

For purulent S. aureus infections (abscesses, furuncles):

• Perform incision and drainage first 2, 1
• Add Bactrim if systemic signs present or extensive infection 2, 1
• Use standard dosing (160/800 mg twice daily) for 5-10 days 1

For non-purulent infections (cellulitis):

• Do NOT use Bactrim alone 1
• Combine with β-lactam if S. aureus suspected alongside streptococci 1

For severe/hospitalized infections:

• Start vancomycin, linezolid, or daptomycin 2, 1
• Consider step-down to Bactrim only after clinical improvement and susceptibility confirmation 2