What antibiotics are used to treat skin infections?

Antibiotics for Skin Infections

First-Line Oral Therapy for Uncomplicated Infections

For mild, non-purulent skin infections (cellulitis), use cephalexin 500 mg every 6 hours, dicloxacillin 250-500 mg every 6 hours, or amoxicillin-clavulanate 875/125 mg twice daily as first-line therapy. 1, 2, 3 These agents provide excellent coverage against streptococci and methicillin-sensitive Staphylococcus aureus (MSSA), the most common pathogens in uncomplicated skin infections. 1, 4

When to Add MRSA Coverage

Add empiric MRSA-active antibiotics if any of the following are present: 2

• Purulent drainage from the wound
• Penetrating trauma or injection drug use
• Evidence of MRSA infection elsewhere on the body
• Known nasal MRSA colonization
• Failed initial beta-lactam therapy

For MRSA coverage, use trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily, doxycycline 100 mg twice daily, or clindamycin 300-450 mg four times daily. 1, 2, 3 These oral agents are highly effective against community-acquired MRSA while maintaining activity against streptococci. 1, 4

Purulent Infections (Abscesses, Furuncles)

Incision and drainage is the primary treatment for purulent infections, with antibiotics serving as adjunctive therapy only. 2 Antibiotics are specifically indicated when: 2

• Fever or systemic signs are present
• Multiple lesions exist
• The patient is immunocompromised
• Drainage alone has failed

Use the same MRSA-active oral regimens listed above (trimethoprim-sulfamethoxazole, doxycycline, or clindamycin) for 5 days if clinical improvement occurs. 1, 2

Severe Infections Requiring Hospitalization

For severe infections with systemic inflammatory response syndrome, hemodynamic instability, or concern for necrotizing infection, initiate IV vancomycin 15-20 mg/kg every 8-12 hours plus piperacillin-tazobactam 3.375 g every 6 hours or a carbapenem (imipenem 500 mg every 6 hours or meropenem 1 g every 8 hours). 1, 5 This broad-spectrum regimen covers MRSA, streptococci, gram-negative organisms, and anaerobes. 1, 5

Alternative IV Regimens by Clinical Scenario

For surgical site infections of trunk/extremity (away from axilla/perineum): 1

• Cefazolin 1 g every 8 hours IV (for MSSA/streptococci)
• Add vancomycin 15 mg/kg every 12 hours if MRSA suspected

For necrotizing fasciitis: 1

• Clindamycin 600-900 mg IV every 8 hours plus piperacillin-tazobactam 4.5 g every 8 hours, with or without vancomycin 1
• Alternative: Ceftriaxone 1 g every 24 hours plus metronidazole 500 mg every 8 hours, with or without vancomycin 1
• For documented group A streptococcal necrotizing fasciitis, use penicillin plus clindamycin 1

Treatment Duration

Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 2 For diabetic foot infections, mild cases require 1-2 weeks while moderate-to-severe infections need 2-4 weeks. 5

Special Situations

Diabetic Foot Infections

For mild infections: 1

• Dicloxacillin, clindamycin, cephalexin, levofloxacin, amoxicillin-clavulanate, or doxycycline
• Add trimethoprim-sulfamethoxazole if MRSA confirmed

For moderate-to-severe infections: 1

• Levofloxacin 750 mg daily, ertapenem 1 g daily, or ampicillin-sulbactam 3 g every 6 hours
• Add vancomycin, linezolid, or daptomycin if MRSA confirmed

Bite Wounds

Use amoxicillin-clavulanate 875/125 mg twice daily orally or ampicillin-sulbactam 1.5-3 g every 6-8 hours IV for animal or human bites. 2, 3 These agents provide essential coverage against both aerobic and anaerobic pathogens commonly found in bite wounds. 2

Recurrent Infections

For patients with 3-4 episodes per year despite treating predisposing factors: 1

• Prophylactic oral penicillin or erythromycin twice daily for 4-52 weeks, OR
• Intramuscular benzathine penicillin every 2-4 weeks

Consider decolonization with intranasal mupirocin twice daily for 5 days plus daily chlorhexidine washes. 2

Critical Pitfalls to Avoid

Do not add MRSA coverage reflexively for all hospitalized patients—MRSA is uncommon in typical cellulitis even in high-prevalence settings. 5 Reserve broad-spectrum therapy for documented severe infections or specific risk factors. 5

Never use clindamycin or metronidazole as monotherapy for mixed infections, as gram-negative coverage is essential. 5 For polymicrobial infections, combination therapy is mandatory. 5

Reassess treatment at 48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens. 5 Prompt surgical consultation is mandatory for necrotizing infections, as antibiotics alone are insufficient and mortality increases dramatically with delayed debridement. 1, 5