What oral antibiotics can I prescribe for a bacterial skin infection in a patient allergic to β‑lactams, metronidazole, sulfonamides, and nitrofurantoin?

Oral Antibiotic Options for Skin Infection with Multiple Drug Allergies

For a bacterial skin infection in a patient allergic to β-lactams, metronidazole, sulfonamides, and nitrofurantoin, prescribe oral clindamycin 300–450 mg three times daily or doxycycline 100 mg twice daily as first-line agents, with linezolid 600 mg twice daily reserved for severe infections or MRSA. 1, 2

First-Line Oral Options

Clindamycin

• Clindamycin is the preferred oral agent for skin and soft tissue infections in penicillin-allergic patients due to excellent activity against Staphylococcus aureus and streptococci. 2
• The Infectious Diseases Society of America recommends clindamycin for both purulent and non-purulent skin infections when β-lactams cannot be used. 1
• Dosing: 300–450 mg orally three times daily for 7–14 days depending on severity. 1

Doxycycline

• Doxycycline is an effective alternative for purulent skin infections, particularly when community-acquired MRSA is suspected. 1
• The IDSA guidelines list doxycycline as an acceptable oral option for MRSA skin infections. 1
• Dosing: 100 mg orally twice daily for 7–10 days. 1
• Avoid in children under 8 years due to dental staining. 2

Second-Line Option for Severe or Refractory Infections

Linezolid

• Linezolid demonstrates superior treatment success compared to vancomycin for skin and soft tissue infections (OR 1.40,95% CI 1.01–1.95) and is FDA-approved for oral use at 600 mg twice daily. 1, 3
• The IDSA recommends linezolid for MRSA infections when first-line agents fail or cannot be used. 1
• Reserve linezolid for moderate-to-severe infections or documented MRSA to minimize resistance development. 2
• Duration: 10–14 days for uncomplicated skin infections, up to 14–28 days for complicated infections. 3

Alternative Considerations

Macrolides (Erythromycin, Azithromycin)

• Macrolides show better cure rates than penicillin for cellulitis (RR 0.84,95% CI 0.73–0.97) and have no structural cross-reactivity with your patient's documented allergies. 1, 4
• However, resistance rates of 20–25% limit macrolides to non-first-line status. 2
• Consider only if clindamycin and doxycycline are contraindicated or unavailable. 1

Critical Pitfalls to Avoid

• Do not use trimethoprim-sulfamethoxazole—your patient has a documented sulfa allergy. 1
• Avoid fluoroquinolones (levofloxacin, moxifloxacin) if the patient has any history of fluoroquinolone allergy, as intra-class cross-reactivity occurs in approximately 10% of cases. 4
• Metronidazole is contraindicated per the patient's allergy history and lacks adequate coverage for typical skin pathogens (S. aureus, streptococci). 1
• Nitrofurantoin is inappropriate for skin infections regardless of allergy status—it achieves inadequate tissue levels and is indicated only for urinary tract infections. 2

Infection-Specific Algorithm

For non-purulent cellulitis (diffuse erythema, warmth, no abscess):

• First choice: Clindamycin 300–450 mg PO TID 1
• Alternative: Doxycycline 100 mg PO BID 1

For purulent infections (abscess, furuncle, carbuncle):

• First choice: Clindamycin 300–450 mg PO TID or doxycycline 100 mg PO BID 1
• If MRSA confirmed or suspected severe: Linezolid 600 mg PO BID 1, 3

For impetigo:

• First choice: Clindamycin 300 mg PO TID 1
• Alternative: Erythromycin (if local resistance patterns permit) 1

Documentation and Follow-Up

• Document the specific allergic reactions (timing, symptoms, severity) for each drug class to guide future antibiotic selection and determine whether allergy testing is warranted. 2, 5
• Over 90% of reported antibiotic allergies are not true IgE-mediated reactions and can potentially be removed after proper assessment. 5
• Arrange outpatient follow-up in 48–72 hours to assess clinical response; switch to linezolid if inadequate improvement on first-line agents. 1