What is a good antibiotic for a patient with probable streptococcal (strep) pharyngitis but possible infectious mononucleosis (mono)?

Antibiotic Selection for Probable Strep Pharyngitis with Possible Mononucleosis

For patients with probable streptococcal pharyngitis but possible infectious mononucleosis, penicillin V or amoxicillin is the recommended first-line treatment, but amoxicillin should be avoided if mononucleosis is strongly suspected due to risk of rash. 1

Diagnostic Approach

Before selecting an antibiotic, proper diagnosis is essential:

1. Apply Centor Criteria to assess likelihood of Group A Streptococcal (GAS) infection:

   • Fever
   • Tonsillar exudates
   • Tender anterior cervical lymphadenopathy
   • Absence of cough 1

2. Testing recommendations:

   • 0-2 Centor criteria: GAS unlikely, no testing needed
   • 3-4 Centor criteria: Test with rapid antigen detection test (RADT) and/or throat culture 1
   • Avoid testing when viral symptoms predominate (cough, rhinorrhea, hoarseness, oral ulcers) 1

3. Consider mononucleosis if:

   • Significant fatigue
   • Generalized lymphadenopathy
   • Splenomegaly
   • Atypical lymphocytes on blood smear

Antibiotic Selection Algorithm

First-line options (if mononucleosis is ruled out):

• Penicillin V: 500 mg 2-3 times daily for adolescents/adults (250 mg 2-3 times daily for children) for 10 days 1
• Amoxicillin: 50 mg/kg once daily (maximum 1000 mg) or 25 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1

When mononucleosis cannot be ruled out:

• Penicillin V: As above (preferred option)
• Cephalexin: 20 mg/kg twice daily (maximum 500 mg per dose) for 10 days 1

For penicillin-allergic patients:

• Clindamycin: 7 mg/kg three times daily (maximum 300 mg per dose) for 10 days 1
• Azithromycin: 12 mg/kg once daily (maximum 500 mg) for 5 days 1

Important Clinical Considerations

• Avoid amoxicillin if mononucleosis is suspected: Amoxicillin can cause a diffuse maculopapular rash in patients with mononucleosis 2

• Bacterial superinfection is uncommon in mononucleosis: Studies show less than 3% of mononucleosis patients have concurrent Group A streptococcal infection 2, 3

• Complete the full antibiotic course: A full 10-day course (except for azithromycin, which is 5 days) is essential to prevent treatment failure, rheumatic fever, and increased bacterial resistance 1

• Treatment failure with penicillin: While historically low (2-10%), penicillin failure rates have increased to approximately 30% in recent decades, often due to poor compliance 4

• Once-daily dosing option: Once-daily amoxicillin (750 mg) has shown comparable effectiveness to three-times-daily penicillin V and may improve compliance 5

Pitfalls to Avoid

• Don't treat viral pharyngitis with antibiotics: Most sore throats are viral and don't require antibiotics 1

• Don't routinely prescribe antibiotics for infectious mononucleosis: Only treat if a bacterial pathogen is confirmed by culture 2, 3

• Don't stop antibiotics early: Incomplete antibiotic courses may lead to treatment failure and complications 1

• Don't miss follow-up: Patients should seek medical attention if symptoms persist or worsen after 48-72 hours of antibiotic therapy 1