What are the first‑line antibiotic choices for a wound infection or abscess in an otherwise healthy adult, and how should they be modified for methicillin‑resistant Staphylococcus aureus risk or mixed aerobic‑anaerobic infection?

First-Line Antibiotics for Wound Infection and Abscess

Incision and Drainage Is Primary Treatment for Abscesses

For any drainable abscess, incision and drainage (I&D) is the definitive treatment and takes priority over antibiotics. 1 In simple abscesses without surrounding cellulitis or systemic features, I&D alone is often sufficient without adjunctive antibiotics. 1, 2, 3

When to Add Antibiotics After I&D

Add systemic antibiotics only when specific high-risk features are present: 1, 2

• Severe or extensive disease involving multiple infection sites 1, 2
• Surrounding cellulitis extending >5 cm from the abscess 1, 2
• Systemic inflammatory response (fever >38°C, tachycardia >90 bpm, hypotension) 1
• Immunosuppression or significant comorbidities (diabetes, HIV, malignancy) 1, 2
• Extremes of age (very young or elderly patients) 1, 2
• Difficult-to-drain locations (face, hand, genitalia) 1, 2
• Lack of clinical improvement 48–72 hours after drainage alone 1, 2

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Wound Infections and Cellulitis Without Abscess

Non-Purulent Cellulitis (No Drainage or Exudate)

Beta-lactam monotherapy is the standard of care, achieving approximately 96% clinical success because the primary pathogens are beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus. 1, 4

First-line oral agents (5 days): 1, 4

• Cephalexin 500 mg orally every 6 hours 1, 4
• Dicloxacillin 250–500 mg orally every 6 hours 1, 4
• Amoxicillin 500 mg orally three times daily 1, 4
• Penicillin V 250–500 mg orally four times daily 1, 4

Treatment duration: Exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, improving erythema, no fever); extend only if symptoms persist. 1, 4

Purulent Cellulitis (Visible Drainage or Exudate, No Drainable Abscess)

Empiric MRSA coverage is mandatory for all purulent cellulitis. 1

First-line oral MRSA-active agents (5 days): 1

• Trimethoprim-sulfamethoxazole (TMP-SMX) 1–2 double-strength tablets orally twice daily – Excellent MRSA coverage but lacks reliable streptococcal activity; must be combined with a beta-lactam (cephalexin or amoxicillin) for non-purulent cellulitis. 1 Avoid in third-trimester pregnancy and infants <2 months. 1

• Doxycycline 100 mg orally twice daily – Covers MRSA but unreliable against streptococci; requires combination with a beta-lactam for non-purulent cellulitis. 1 Contraindicated in children <8 years (tooth discoloration, bone growth effects) and pregnancy category D. 1

• Clindamycin 300–450 mg orally every 6–8 hours – Provides single-agent coverage for both MRSA and streptococci, eliminating need for combination therapy. 1, 2 Use only when local MRSA clindamycin resistance is <10%; higher rates of Clostridioides difficile infection compared to other oral agents. 1, 2

• Linezolid 600 mg orally twice daily – Effective MRSA and streptococcal coverage but significantly more expensive than alternatives. 1

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When to Add MRSA Coverage to Beta-Lactam Therapy

Do not routinely add MRSA coverage for typical non-purulent cellulitis. MRSA is an uncommon cause even in high-prevalence settings. 1, 4

Add MRSA-active antibiotics only when any of these risk factors are present: 1, 4

• Penetrating trauma or injection drug use 1, 4
• Visible purulent drainage or exudate 1, 4
• Known MRSA colonization or prior MRSA infection 1, 4
• Systemic inflammatory response syndrome (fever, tachycardia, tachypnea) 1, 4
• Failure to respond to beta-lactam therapy after 48–72 hours 1, 4

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Hospitalized Patients with Complicated Infections

For patients requiring IV therapy, vancomycin 15–20 mg/kg IV every 8–12 hours (target trough 15–20 mg/L) is first-line for MRSA coverage. 1, 2

Alternative IV MRSA-active agents (all A-I evidence): 1, 2

• Linezolid 600 mg IV twice daily 1, 2
• Daptomycin 4 mg/kg IV once daily (6 mg/kg for bacteremia) 1, 2, 5
• Clindamycin 600 mg IV every 8 hours (only if local MRSA resistance <10%) 1

For severe cellulitis with systemic toxicity or suspected necrotizing infection, use broad-spectrum combination therapy: 1, 4

• Vancomycin 15–20 mg/kg IV every 8–12 hours PLUS piperacillin-tazobactam 3.375–4.5 g IV every 6 hours 1, 4
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1, 4
• Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1, 4

Duration for complicated infections: 7–14 days, individualized based on clinical response. 1, 2

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Surgical Site Infections (SSI)

The primary and most important therapy for SSI is to open the incision, evacuate infected material, and continue dressing changes until the wound heals by secondary intention. 1 Studies of subcutaneous abscesses found no benefit for antibiotic therapy when combined with drainage. 1

If minimal surrounding invasive infection (<5 cm erythema/induration) and minimal systemic signs (temperature <38.5°C, pulse <100 bpm), antibiotics are unnecessary. 1

For patients with temperature ≥38.5°C or pulse ≥100 bpm, a short course of antibiotics (24–48 hours) may be indicated. 1

Antibiotic selection for SSI: 1

• Clean procedures (not entering intestinal/genital tracts): Target S. aureus (including MRSA) and streptococci. Use vancomycin, daptomycin, or linezolid if MRSA rate is high. 1
• Operations on intestinal tract or female genitalia: Mixed gram-positive/gram-negative flora with anaerobes; use any antibiotic appropriate for intra-abdominal infection. 1
• Axillary incisions: Significant gram-negative organisms; adjust coverage accordingly. 1
• Perineal incisions: Higher incidence of gram-negatives and anaerobes; adjust coverage accordingly. 1

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Pediatric Dosing

Oral MRSA-active regimens for children: 1

• Clindamycin: 10–13 mg/kg/dose every 6–8 hours (max 40 mg/kg/day) 1, 2
• TMP-SMX: 4–6 mg/kg/dose (trimethoprim component) twice daily 1, 2
• Doxycycline: 2 mg/kg/dose twice daily (only ≥8 years, <45 kg) 1

IV therapy for hospitalized children: 1

• Vancomycin: 15 mg/kg IV every 6 hours (first-line) 1
• Clindamycin: 10–13 mg/kg IV every 6–8 hours (if stable, no bacteremia, local resistance <10%) 1
• Linezolid: 10 mg/kg IV every 8 hours (max 600 mg/dose) 1

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Critical Pitfalls to Avoid

• Do not prescribe antibiotics for simple abscesses that can be adequately drained unless high-risk features are present. 1, 2, 6, 3
• Do not use beta-lactams (cephalexin, dicloxacillin, amoxicillin) for MRSA coverage; they lack activity due to mecA-mediated resistance. 2, 7
• Do not use doxycycline or TMP-SMX as monotherapy for typical non-purulent cellulitis; they lack reliable streptococcal coverage. 1, 4
• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors; this overtreats ~96% of cases and promotes resistance. 1, 4
• Do not automatically extend therapy to 7–10 days; extend only if warmth, tenderness, or erythema persist after 5 days. 1, 4
• Do not delay surgical consultation when signs of necrotizing infection appear (severe pain out of proportion, skin anesthesia, rapid progression, "wooden-hard" tissue, gas, bullae). 1, 4

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Adjunctive Measures

• Elevate the affected extremity above heart level for ≥30 minutes three times daily to promote gravity drainage of edema. 1, 4
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration; treat to reduce recurrence. 1, 4
• Address predisposing conditions (venous insufficiency, lymphedema, chronic edema, obesity, eczema). 1, 4
• Keep draining wounds covered with clean, dry bandages and maintain good hand hygiene. 2