Best Antibiotics for Skin Infections

For uncomplicated skin infections, dicloxacillin, cephalexin, clindamycin, or amoxicillin-clavulanate are the recommended first-line treatments, with selection based on suspected pathogens and local resistance patterns. 1

Antibiotic Selection by Infection Type

Impetigo

Dicloxacillin 250 mg four times daily (PO) 2, 1
Cephalexin 250 mg four times daily (PO) 2, 1
Erythromycin 250 mg four times daily (PO) - note that some strains of S. aureus and S. pyogenes may be resistant 2
Mupirocin ointment applied three times daily (for limited number of lesions) 2, 1

Methicillin-Susceptible S. aureus (MSSA) Infections

Nafcillin or oxacillin 1-2 g every 4 hours (IV) - parenteral drug of choice 2
Dicloxacillin 500 mg four times daily (PO) - oral agent of choice 2, 1
Cephalexin 500 mg four times daily (PO) - for penicillin-allergic patients (except those with immediate hypersensitivity reactions) 2
Clindamycin 300-450 mg three times daily (PO) or 600 mg every 8 hours (IV) 2, 1

Methicillin-Resistant S. aureus (MRSA) Infections

Vancomycin 30 mg/kg/day in 2 divided doses (IV) - parenteral drug of choice 2
Linezolid 600 mg twice daily (PO or IV) - shown to have 79% cure rate for MRSA skin infections 3
Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily (PO) 2, 1
Doxycycline 100 mg twice daily (PO) - not recommended for children under 8 years 2, 1
Clindamycin 300-450 mg three times daily (PO) or 600 mg every 8 hours (IV) - caution with inducible resistance 2

Mixed/Complicated Infections

Amoxicillin-clavulanate 875/125 mg twice daily (PO) 2, 1
Piperacillin-tazobactam plus vancomycin (IV) for severe mixed infections 2

Duration of Therapy

For uncomplicated skin infections: 7-10 days of therapy is typically recommended 2, 1
For streptococcal infections: minimum of 10 days to prevent rheumatic fever 1
For more severe infections: 7-14 days, individualized based on clinical response 1

Special Considerations

Efficacy Comparisons

Cephalexin and dicloxacillin have shown equal effectiveness in treating staphylococcal skin infections, with cure rates of approximately 90% 4
Cephalexin has the advantage of twice-daily dosing which may enhance compliance 4
For simple abscesses, incision and drainage alone may be sufficient, with one study showing 90.5% cure rate without antibiotics 5

Topical vs. Systemic Treatment

For localized infections limited to external skin layers, topical treatment may be adequate 6
Topical options like retapamulin, fusidic acid, and mupirocin have shown significant efficacy in reducing bacterial loads in experimental models 7
For widespread or deeper infections, systemic treatment is necessary 6

Antibiotic Selection Algorithm

Determine infection severity and likely pathogens:
- Mild, localized (e.g., impetigo): Consider topical agents or oral anti-staphylococcal penicillins/cephalosporins 2, 1
- Moderate to severe: Use systemic antibiotics 2, 1
Consider local MRSA prevalence:
- Low MRSA risk: Dicloxacillin or cephalexin 2, 8
- High MRSA risk or confirmed MRSA: Trimethoprim-sulfamethoxazole, doxycycline, or linezolid 2, 3
For purulent infections:
- Incision and drainage is crucial 2, 5
- For simple abscesses, antibiotics may not be necessary after adequate drainage 5
For diabetic foot infections or complicated skin infections:
- Broader coverage with agents like amoxicillin-clavulanate or piperacillin-tazobactam plus vancomycin 2, 3
For animal or human bites:
- Amoxicillin-clavulanate is recommended due to mixed flora often present 2, 1

Pitfalls and Caveats

Increasing prevalence of community-acquired MRSA makes empiric beta-lactam therapy potentially ineffective 5
Erythromycin resistance is common in both S. aureus and S. pyogenes 2
Clindamycin may have inducible resistance in MRSA strains 2
Culture and sensitivity testing is recommended for treatment failures, recurrent infections, or severe infections 1

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