What is the initial antibiotic treatment for skin and soft tissue infections?

Initial Antibiotic Treatment for Skin and Soft Tissue Infections

For typical non-purulent cellulitis/erysipelas, start with oral cephalexin 500 mg every 6 hours or dicloxacillin for 5-7 days, as these penicillinase-resistant agents provide optimal coverage against the most common pathogens (Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus) without unnecessary MRSA coverage. 1, 2

Classification-Based Treatment Algorithm

Purulent SSTIs (Abscesses, Carbuncles, Furuncles)

Primary intervention:

• Incision and drainage is the definitive treatment and often sufficient alone 1
• Gram stain and culture are recommended but treatment without these studies is reasonable in typical cases 1

Adjunctive antibiotics indicated when:

• Systemic signs present (temperature >38°C, heart rate >90 bpm, respiratory rate >24 bpm, WBC <12,000 or >4,000 cells/μL) 1
• Multiple sites of infection 1
• Rapid progression with surrounding cellulitis 1
• Immunocompromised state 1

Antibiotic choices for purulent infections:

• Oral options: Trimethoprim-sulfamethoxazole (TMP-SMX), doxycycline, or clindamycin (all provide MRSA coverage) 1, 2
• IV options (severe cases): Vancomycin 15 mg/kg every 12 hours, linezolid 600 mg every 12 hours, or daptomycin 1, 2

Non-Purulent SSTIs (Cellulitis/Erysipelas)

Mild infection (no systemic signs):

• First-line: Cephalexin 500 mg every 6 hours OR dicloxacillin 500 mg every 6 hours orally 1, 2
• Alternative: Amoxicillin-clavulanate 875 mg every 12 hours 1, 2
• Penicillin-allergic: Clindamycin 300-450 mg every 8 hours (99.5% of S. pyogenes remain susceptible) 2
• Duration: 5 days if clinical improvement evident; extend only if no improvement 1, 2

Moderate infection (systemic signs present):

• Oral: Same agents as mild infection but consider hospitalization for observation 1
• IV (if hospitalized): Cefazolin 1-2 g every 8 hours OR nafcillin 2 g every 6 hours 1, 2

Severe infection (failed oral therapy, systemic toxicity, immunocompromised, deeper infection signs):

• Broad empiric coverage: Vancomycin 15 mg/kg every 12 hours PLUS piperacillin-tazobactam 3.375-4.5 g every 6-8 hours OR a carbapenem 1
• Alternative: Vancomycin PLUS ceftriaxone 1 g every 24 hours AND metronidazole 500 mg every 8 hours 1

When to Add MRSA Coverage

MRSA is an unusual cause of typical cellulitis and routine coverage is unnecessary 2

Add MRSA-active agents when:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate visible 2
• Evidence of MRSA infection elsewhere or known nasal colonization 2
• Systemic inflammatory response syndrome (SIRS) criteria present 2
• Failed initial beta-lactam therapy after 48-72 hours 2

MRSA coverage options:

• Oral: Clindamycin 300-450 mg every 8 hours (covers both streptococci and MRSA) OR TMP-SMX 1-2 double-strength tablets every 12 hours PLUS a beta-lactam (cephalexin, penicillin, or amoxicillin) for streptococcal coverage 2
• IV: Vancomycin, linezolid 600 mg every 12 hours, or daptomycin 4 mg/kg daily 2, 3

Necrotizing Fasciitis (Severe Non-Purulent)

Immediate surgical consultation is mandatory 1

Empiric broad-spectrum coverage:

• Vancomycin OR linezolid 600 mg every 12 hours PLUS piperacillin-tazobactam OR a carbapenem OR ceftriaxone 1 g every 24 hours AND metronidazole 500 mg every 8 hours 1

Documented Group A Streptococcus:

• Penicillin G 4 million units every 4 hours PLUS clindamycin 600-900 mg every 8 hours 1

Impetigo/Ecthyma

Oral therapy for 7 days:

• First-line (MSSA expected): Dicloxacillin or cephalexin 1
• MRSA suspected/confirmed: Doxycycline, clindamycin, or TMP-SMX 1
• Streptococci alone on culture: Oral penicillin 1

Critical Considerations

Treatment Duration

• Standard: 5 days is as effective as 10 days for uncomplicated cellulitis if clinical improvement occurs 1, 2
• Extend beyond 5 days only if infection has not improved 2
• Diabetic patients: May require longer duration than non-diabetic patients 2

Hospitalization Criteria

• SIRS criteria (fever, altered mental status, hemodynamic instability) 2
• Concern for deeper or necrotizing infection 2
• Severe immunocompromise 2
• Failure of outpatient treatment after 24-48 hours 2
• Poor adherence anticipated 2

Adjunctive Measures

• Elevate affected extremity to promote drainage 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration 2
• Treat predisposing conditions (venous insufficiency, lymphedema, eczema) 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to hasten resolution 2

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors 2
• Do not use TMP-SMX as monotherapy for typical cellulitis unless in high MRSA-prevalence area with purulent features; it lacks adequate streptococcal coverage 2
• Do not automatically extend treatment to 10 days; reassess at 5 days and extend only if no improvement 2
• Do not use systemic corticosteroids in diabetic patients despite potential benefit in non-diabetics 2
• Do not obtain blood cultures for typical cellulitis; they are positive in only 5% of cases 2

Monitoring Response

• Reassess outpatients within 24-48 hours to ensure clinical improvement 2
• If no improvement with appropriate first-line antibiotics, consider resistant organisms, cellulitis mimickers (DVT, gout, stasis dermatitis), or underlying complications (abscess, osteomyelitis) 2
• Obtain blood cultures and tissue cultures only in patients with severe systemic features, malignancy, neutropenia, or unusual predisposing factors 2