Why not prescribe Penicillin (PCN) for infectious mononucleosis (mono)?

From the Guidelines

Penicillin (PCN) should not be prescribed for infectious mononucleosis (mono) due to the high risk of a non-allergic rash and the fact that mono is a viral infection, making antibiotics ineffective against the underlying cause. The use of penicillin in patients with mono can lead to a rash in up to 90% of cases, as noted in various studies 1. This rash is not an allergic reaction but rather a specific response to the combination of the Epstein-Barr virus (EBV) infection and penicillin or its derivatives. Key points to consider in the management of mono include:

• The infection is caused by EBV, a virus, making antibiotics like penicillin ineffective against the underlying infection.
• Treatment should focus on supportive care, including:
  • Adequate rest
  • Hydration
  • Pain control with acetaminophen or NSAIDs for fever and sore throat
• If a bacterial superinfection, such as streptococcal pharyngitis, is suspected alongside mono, alternative antibiotics like clindamycin or macrolides should be considered instead of penicillins to avoid triggering the characteristic rash, as suggested by guidelines for the management of acute sore throat 1. Given the most recent and highest quality evidence, the recommendation is to avoid penicillin in the treatment of mono and instead opt for supportive care and alternative antibiotics if a bacterial superinfection is present, to minimize the risk of the non-allergic rash and to address any potential bacterial complications effectively 1.

From the FDA Drug Label

1. 5 Skin Rash in Patients with Mononucleosis A high percentage of patients with mononucleosis who receive amoxicillin develop an erythematous skin rash. Thus, amoxicillin should not be administered to patients with mononucleosis.

Amoxicillin, a type of penicillin, should not be prescribed for patients with mononucleosis due to a high risk of developing an erythematous skin rash 2.

From the Research

Why Not Prescribe PCN for Mono

• Penicillin (PCN) is not typically prescribed for infectious mononucleosis (mono) because the disease is caused by the Epstein-Barr virus (EBV), which is a viral infection, not a bacterial infection 3, 4, 5, 6, 7.
• The use of antibiotics, such as PCN, is not recommended for the treatment of viral infections like mono, as they are ineffective against viruses and may contribute to antibiotic resistance 3, 5, 7.
• Symptomatic treatment, including adequate hydration, analgesics, antipyretics, and rest, is the mainstay of care for patients with mono 3, 4, 5, 7.
• Corticosteroids may be beneficial in certain cases, such as respiratory compromise or severe pharyngeal edema, but their use is not routine and should be individualized 3, 4, 5.
• The diagnosis of mono is typically made based on clinical presentation, laboratory tests, such as a heterophile antibody test or EBV-specific antibody profiles, and complete blood count with differential 4, 5, 6, 7.

Complications and Considerations

• Patients with mono should be advised to avoid contact sports or strenuous exercise for a period of time, typically 3-4 weeks, to reduce the risk of splenic rupture 3, 4, 5, 7.
• Immunosuppressed populations are at higher risk of severe disease and significant morbidity, and may require closer monitoring and individualized treatment plans 4, 7.
• EBV infection has been linked to certain types of cancer and autoimmune diseases, highlighting the importance of prompt diagnosis and management of mono 6, 7.