What is the recommended treatment for a skin infection in a patient with a penicillin (PCN) allergy?

Treatment of Skin Infections in Patients with Penicillin Allergy

For patients with penicillin allergy who have skin infections, clindamycin is recommended as the first-line antibiotic treatment due to its excellent coverage of common causative organisms and established safety profile. 1

First-Line Oral Treatment Options

• Clindamycin is the preferred first-line agent for skin and soft tissue infections in penicillin-allergic patients 1
• Doxycycline 100 mg orally twice daily for 7-14 days is an effective alternative for adults (not recommended for children under 8 years) 1, 2
• Trimethoprim-sulfamethoxazole (1-2 double-strength tablets twice daily) is particularly effective for suspected MRSA infections 1
• Tetracycline 500 mg orally four times a day for 2 weeks is another alternative, though compliance may be better with doxycycline 3
• Erythromycin 500 mg orally four times a day for 2 weeks can be used, but is considered less effective than other recommended regimens 3

Treatment Based on Infection Severity

For Non-Severe Infections:

• Oral antibiotics as listed above are appropriate for uncomplicated skin infections 1
• Treatment duration should be kept to the shortest effective period, typically 7-10 days for uncomplicated infections 3

For Severe Infections Requiring IV Therapy:

• Vancomycin is the drug of choice for severe infections in penicillin-allergic patients (30 mg/kg/day in 2 divided doses IV), especially for MRSA coverage 1, 4
• IV clindamycin (600 mg every 8 hours) is effective for both MSSA and MRSA when parenteral therapy is needed 1
• Linezolid (600 mg every 12 hours IV or orally) should be reserved for more resistant infections or when other options fail 1, 4

Antibiotic Selection Based on Allergy Type

• For patients with severe/immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm, or anaphylaxis), avoid all beta-lactam antibiotics including cephalosporins 3, 1
• For patients with non-immediate or unclear penicillin allergy history, consider allergy assessment and penicillin skin testing when appropriate 3
• Properly performed skin testing using major and minor penicillin determinant reagents has a negative predictive value of 97%-99% 3

Special Considerations

• Patients labeled as having a penicillin allergy are exposed to more alternative antibiotics and have increased prevalence of C. difficile, MRSA, and vancomycin-resistant enterococcal infections 3
• For mixed aerobic/anaerobic infections, consider clindamycin with either a fluoroquinolone or metronidazole 1
• If penicillin is absolutely necessary for treatment (e.g., in life-threatening infections), desensitization should be considered under careful monitoring 3, 5, 6
• Penicillin skin testing is safe and effective even in immunocompromised patients, with studies showing 95% negative results and no immediate-type allergic reactions when these patients subsequently received penicillin-based antibiotics 7

Common Pitfalls and Caveats

• Avoid assuming all patients with a reported penicillin allergy have true IgE-mediated hypersensitivity; approximately 90% of patients who report penicillin allergy can safely receive penicillins after proper evaluation 3, 8
• Cephalosporins are contraindicated in patients with immediate penicillin hypersensitivity (urticaria, angioedema, bronchospasm, or anaphylaxis) 4
• Single-dose ceftriaxone therapy is not effective for treating syphilis and should not be used as an alternative in penicillin-allergic patients with skin infections caused by syphilis 3
• When using clindamycin, be aware of the risk of Clostridioides difficile infection, particularly with prolonged use 1