Antibiotic Selection for Skin Infections
For uncomplicated skin infections, prescribe cephalexin 500 mg four times daily or dicloxacillin 500 mg four times daily for methicillin-susceptible Staphylococcus aureus (MSSA), and use trimethoprim-sulfamethoxazole, doxycycline, or clindamycin for suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA). 1
Initial Assessment and Antibiotic Selection Algorithm
The choice of antibiotic depends on three critical factors: infection type (purulent vs. non-purulent), severity, and local MRSA prevalence 1, 2.
For Purulent Infections (Abscesses, Furuncles, Carbuncles)
- Incision and drainage is the primary treatment for abscesses; antibiotics are adjunctive 1
- For mild purulent infections after drainage, consider observation without antibiotics if systemically well 1
- If antibiotics are needed for purulent infections, empiric MRSA coverage is essential: 1, 2
For Non-Purulent Infections (Cellulitis, Erysipelas)
Mild cellulitis without systemic signs:
- Cephalexin 500 mg four times daily (covers streptococci and MSSA) 1, 2
- Dicloxacillin 500 mg four times daily (alternative for MSSA coverage) 1, 2
- Clindamycin 300-400 mg four times daily (for penicillin-allergic patients) 1
Moderate cellulitis with systemic signs (fever, tachycardia):
- Many clinicians add MSSA coverage to streptococcal coverage 1
- Consider cephalexin or dicloxacillin as above 1
Severe cellulitis with SIRS or risk factors for MRSA:
- Risk factors include: penetrating trauma, injection drug use, nasal MRSA colonization, or prior MRSA infection 1
- Vancomycin 30 mg/kg/day in 2 divided doses IV (parenteral drug of choice for MRSA) 1
- Linezolid 600 mg twice daily IV or oral (alternative with excellent bioavailability) 1, 3
For Impetigo
- Mupirocin ointment applied twice daily for limited lesions 1, 2
- Cephalexin 250 mg four times daily for more extensive disease 1
- Dicloxacillin 250 mg four times daily (alternative) 1
- Avoid erythromycin due to increasing resistance in S. aureus and S. pyogenes 1
Duration of Therapy
- 5 days is recommended for cellulitis, extended if not improved 1
- 7 days for most purulent infections and impetigo 1, 2
- 10 days minimum for streptococcal infections to prevent rheumatic fever 2
- 7-14 days for more severe infections based on clinical response 2
Critical Pitfalls to Avoid
The most common error is using cephalexin or dicloxacillin for purulent infections without drainage, as these agents lack MRSA coverage and MRSA is the predominant pathogen in abscesses 4. A 2023 real-world study found that 82% of patients with purulent infections received inappropriate antibiotics, primarily because clinicians used agents ineffective against MRSA 4.
For cellulitis, avoid empiric MRSA coverage unless specific risk factors are present, as streptococci remain the primary pathogen in typical cellulitis 1. Overuse of broad-spectrum agents drives resistance 4.
Check local antibiograms before prescribing clindamycin, as inducible resistance in MRSA strains can lead to treatment failure despite in vitro susceptibility 1, 5.
Pediatric Dosing Adjustments
- Cephalexin: 25-50 mg/kg/day in 3-4 divided doses 1, 2
- Dicloxacillin: 25-50 mg/kg/day in 4 divided doses 1
- Clindamycin: 20-30 mg/kg/day in 3 divided doses 1
- Trimethoprim-sulfamethoxazole: 8-12 mg/kg/day (based on trimethoprim) in 2 divided doses 1
- Avoid doxycycline in children under 8 years 1, 2
Special Populations
For hospitalized patients requiring IV therapy:
- Nafcillin or oxacillin 1-2 g every 4 hours IV for MSSA 1
- Cefazolin 1 g every 8 hours IV for penicillin-allergic patients (non-anaphylactic) 1
- Vancomycin for MRSA or severe infections 1
For recurrent MRSA infections:
- After treating the acute infection with appropriate antibiotics, consider a 5-day decolonization regimen with intranasal mupirocin twice daily, daily chlorhexidine washes, and decontamination of personal items 1