What is the recommended treatment for a young adult with concurrent infectious mononucleosis (mono) and streptococcal pharyngitis (strep)?

Treating Streptococcal Pharyngitis in Patients with Concurrent Infectious Mononucleosis

Only treat streptococcal pharyngitis in patients with concurrent infectious mononucleosis if you have a positive throat culture or rapid antigen detection test confirming Group A Streptococcus, and avoid amoxicillin/ampicillin entirely due to the high risk of maculopapular rash. 1, 2

The Critical Context: Concurrent Infection is Uncommon

• Only 4% of patients meeting strict diagnostic criteria for infectious mononucleosis have concurrent Group A beta-hemolytic streptococcal pharyngitis confirmed by throat culture 2
• The clinical presentations of IM and streptococcal pharyngitis overlap significantly, making empiric antibiotic treatment unjustified without microbiologic confirmation 2
• Testing is mandatory: Neither conventional throat culture nor rapid antigen detection tests differentiate acutely infected persons from asymptomatic Streptococcus carriers with intercurrent viral pharyngitis, but they allow you to withhold antibiotics from the majority of patients 1

When Strep is Confirmed: Antibiotic Selection Algorithm

AVOID Amoxicillin and Ampicillin Completely

• These penicillins cause a characteristic maculopapular rash in patients with infectious mononucleosis and should never be used in this setting (general medical knowledge, though not explicitly cited in provided evidence)

First-Line Treatment: Penicillin V

• Penicillin V remains the drug of choice when strep is confirmed in a patient with concurrent IM 1, 3
• Dosing for adolescents and adults: 250 mg orally three to four times daily OR 500 mg twice daily for 10 days 1, 3
• Dosing for children: 250 mg orally two to three times daily for 10 days 1, 3
• Penicillin V has proven efficacy, narrow spectrum, safety, and low cost, with no documented resistance in Group A Streptococcus anywhere in the world 3

Alternative: Intramuscular Benzathine Penicillin G

• For adolescents and adults: 1.2 million units as a single intramuscular dose 1
• For children weighing <27 kg: 600,000 units as a single intramuscular dose 1
• This option eliminates compliance concerns and ensures adequate treatment duration 1

Treatment for Penicillin-Allergic Patients

Non-Immediate (Non-Anaphylactic) Penicillin Allergy

• First-generation cephalosporins are preferred: Cephalexin 500 mg orally twice daily for 10 days (adults) or 20 mg/kg per dose twice daily for 10 days (children) 4, 3
• Alternative: Cefadroxil 30 mg/kg once daily (maximum 1 gram) for 10 days 4, 3
• Cross-reactivity risk is only 0.1% in patients with non-severe, delayed penicillin reactions 4

Immediate/Anaphylactic Penicillin Allergy

• Clindamycin is the preferred choice: 300 mg orally three times daily for 10 days (adults) or 7 mg/kg per dose three times daily (maximum 300 mg/dose) for 10 days (children) 4, 3
• Clindamycin has approximately 1% resistance among Group A Streptococcus in the United States and demonstrates high efficacy even in chronic carriers 4
• Avoid all beta-lactams (including cephalosporins) due to up to 10% cross-reactivity risk in patients with immediate hypersensitivity 4

Macrolides: Use with Caution

• Azithromycin 500 mg once on day 1, then 250 mg once daily for days 2-5 (adults) or 12 mg/kg once daily (maximum 500 mg) for 5 days (children) 4, 5
• Macrolide resistance is 5-8% in the United States and varies geographically 4
• Azithromycin is FDA-approved as an alternative to first-line therapy in individuals who cannot use first-line therapy, but data establishing efficacy in preventing rheumatic fever are not available 5
• Clinical success rates are similar to penicillin (95% vs 97%), but bacteriologic eradication is significantly lower (38% vs 81% at day 14) 6

Critical Treatment Duration Requirements

• A full 10-day course is mandatory for all antibiotics except azithromycin to achieve maximal pharyngeal eradication and prevent acute rheumatic fever 1, 3, 7
• Therapy must be sufficient to eliminate the organism; otherwise, sequelae of streptococcal disease (including rheumatic fever) may occur 7
• Azithromycin requires only 5 days due to its prolonged tissue half-life 4, 3
• Shortening courses below 10 days (except azithromycin) dramatically increases treatment failure rates and rheumatic fever risk 4, 3

Common Pitfalls to Avoid

• Never use amoxicillin or ampicillin in patients with known or suspected infectious mononucleosis due to rash risk
• Do not treat empirically without microbiologic confirmation - only 4% of IM patients have concurrent strep 2
• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to 10% cross-reactivity 4
• Do not use trimethoprim-sulfamethoxazole - it fails to eradicate streptococci effectively 8
• Do not shorten antibiotic courses below recommended durations, as this increases treatment failure and complications 4, 3

Adjunctive Symptomatic Management

• Acetaminophen or NSAIDs (such as ibuprofen) for moderate to severe symptoms or high fever 4, 3
• Avoid aspirin in children due to Reye syndrome risk 4
• Corticosteroids are not recommended 4