What is the treatment for streptococcal (strep) infection in patients with a penicillin (PCN) allergy?

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Last updated: April 22, 2025View editorial policy

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From the Guidelines

For patients with penicillin allergies, the most recommended treatment for streptococcal infections is Cephalexin, 20 mg/kg/dose twice daily (max = 500 mg/dose) for 10 days, as it has a strong, high recommendation strength and quality 1. When considering treatment options for patients allergic to penicillin, it's crucial to weigh the benefits and risks of each alternative antibiotic.

  • Cephalexin and Cefadroxil are both first-line alternatives, but they should be avoided in individuals with immediate-type hypersensitivity to penicillin 1.
  • Macrolides like Azithromycin, 12 mg/kg once daily (max = 500 mg) for 5 days, and Clarithromycin, 7.5 mg/kg/dose twice daily (max = 250 mg/dose) for 10 days, are also effective options, although resistance to these agents is well-known and varies geographically and temporally 1.
  • Clindamycin, 7 mg/kg/dose three times daily (max = 300 mg/dose) for 10 days, is another alternative with a strong, moderate recommendation strength and quality 1. It's essential to consider the severity of the infection, the patient's allergy history, local resistance patterns, and patient-specific factors like age and kidney function when choosing an antibiotic 1.
  • The patient should complete the full course of antibiotics, even if symptoms improve, to prevent recurrence and antibiotic resistance.
  • In clinical practice, the choice of antibiotic should prioritize the patient's safety, the effectiveness of the treatment, and the prevention of potential complications, such as acute rheumatic fever and poststreptococcal glomerulonephritis 1.

From the FDA Drug Label

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. NOTE: Penicillin by the intramuscular route is the usual drug of choice in the treatment of Streptococcus pyogenes infection and the prophylaxis of rheumatic fever. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx In cases of β-hemolytic streptococcal infections, treatment should continue for at least 10 days.

For patients allergic to penicillin (PCN), azithromycin or clindamycin can be used as an alternative for the treatment of strep infections.

  • Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx.
  • Clindamycin can be used to treat β-hemolytic streptococcal infections, with a treatment duration of at least 10 days 2 3.

From the Research

Strep Treatment for PCN Allergic Patients

  • For patients allergic to penicillin, alternative antibiotics such as macrolides (e.g., azithromycin, clarithromycin) can be used to treat strep infections 4, 5.
  • Azithromycin and clarithromycin have been shown to be effective in treating streptococcal pharyngitis, acute sinusitis, and other infections 4, 5.
  • However, it's essential to note that many patients who report a penicillin allergy may not have a clinically significant reaction, and evaluation of penicillin allergy before deciding on alternative antibiotics is crucial for antimicrobial stewardship 6.
  • Penicillin skin testing can be used to exclude the risk of IgE-mediated reactions, and desensitization therapy can be performed if penicillin is the first choice for treatment 7.
  • A study found that using a penicillin allergy history algorithm and subsequent penicillin skin testing can safely transition patients from second-line to first-line antibiotic therapy, including β-lactam antibiotics 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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