Dosing of Bactrim with Augmentin for Cellulitis
Direct Answer
Do not combine Bactrim (trimethoprim-sulfamethoxazole) with Augmentin (amoxicillin-clavulanate) for typical cellulitis—this represents unnecessary polypharmacy that provides no additional benefit and increases adverse effects. 1
Treatment Algorithm for Cellulitis
For Typical Nonpurulent Cellulitis (No Abscess, No Purulent Drainage)
Use beta-lactam monotherapy only:
- Augmentin 875/125 mg twice daily for 5 days is appropriate as a single agent for typical cellulitis 1
- Alternative beta-lactams include cephalexin 500 mg four times daily or dicloxacillin 500 mg four times daily 1
- Beta-lactam monotherapy is successful in 96% of cases—MRSA coverage is NOT needed 1
- Extend treatment beyond 5 days only if symptoms have not improved within this timeframe 1
Do NOT add Bactrim to Augmentin in this scenario because:
- Augmentin already provides adequate streptococcal coverage (the primary pathogen) 1
- Adding Bactrim provides no additional benefit for typical cellulitis 2
- Combination therapy increases adverse effects without improving outcomes 1
For Purulent Cellulitis or MRSA Risk Factors
When MRSA coverage IS needed (penetrating trauma, purulent drainage, injection drug use, known MRSA colonization, or systemic inflammatory response syndrome), use ONE of these regimens 1:
- Clindamycin 300-450 mg three times daily alone (covers both streptococci and MRSA in a single drug) 1, 3
- Bactrim 160-800 mg (one double-strength tablet) twice daily PLUS a beta-lactam (cephalexin or amoxicillin, NOT Augmentin) 1
- Doxycycline 100 mg twice daily PLUS a beta-lactam 1
Critical distinction: If you need MRSA coverage, Bactrim must be combined with a simple beta-lactam (like cephalexin or amoxicillin), not Augmentin, because the clavulanate component in Augmentin is unnecessary and adds cost/side effects without benefit 1. Alternatively, use clindamycin monotherapy to avoid polypharmacy entirely 1, 3.
For Bite-Related Cellulitis
Augmentin 875/125 mg twice daily as monotherapy is the preferred agent for animal or human bite-associated cellulitis because it provides single-agent coverage for polymicrobial oral flora 4, 1. Do NOT add Bactrim in this scenario 4.
Evidence Strength and Nuances
The 2014 IDSA guidelines explicitly state that Bactrim has "good activity against aerobes; poor activity against anaerobes" and list it as an option for bite wounds only when combined with metronidazole 4. For typical cellulitis, a landmark randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no benefit: 85% cure rate with combination therapy versus 82% with cephalexin alone (risk difference 2.7%, 95% CI -9.3% to 15%, P=0.66) 2. This confirms that MRSA coverage is unnecessary for typical nonpurulent cellulitis 2.
Retrospective data from Hawaii (high MRSA prevalence area) showed trimethoprim-sulfamethoxazole had higher success rates than cephalexin (91% vs 74%, P<0.001), but this study included patients with purulent infections and MRSA risk factors 5. This does NOT justify routine combination therapy—it supports using MRSA-active agents when risk factors are present 5.
A 2019 retrospective study found that amoxicillin-clavulanate monotherapy was associated with the shortest hospital stays for erysipelas/cellulitis compared to cephalosporins or clindamycin 6, further supporting beta-lactam monotherapy for typical cases.
Common Pitfalls to Avoid
- Never use Bactrim as monotherapy for cellulitis—it lacks reliable activity against beta-hemolytic streptococci, the primary pathogen 1
- Never combine Bactrim with Augmentin—if MRSA coverage is needed, use Bactrim with a simple beta-lactam (cephalexin/amoxicillin) or switch to clindamycin monotherapy 1, 3
- Do not reflexively add MRSA coverage simply because MRSA prevalence is high in your area—typical nonpurulent cellulitis is caused by streptococci even in high-MRSA settings 1, 2
- Assess for abscess with ultrasound if clinically uncertain—purulent collections require incision and drainage plus MRSA-active antibiotics, not just antibiotics alone 1