Antibiotic Treatment for Concurrent Strep Pharyngitis and Infectious Mononucleosis
Avoid ampicillin and amoxicillin entirely in patients with concurrent streptococcal pharyngitis and infectious mononucleosis, as these agents cause a characteristic maculopapular rash in up to 90% of mono patients; instead, use a first-generation cephalosporin (such as cephalexin) or a macrolide (such as azithromycin or erythromycin) if antibiotic treatment is indicated for documented Group A streptococcal infection. 1
Key Clinical Decision Points
First: Confirm Both Diagnoses
- Document Group A streptococcal pharyngitis with either throat culture or rapid antigen detection testing (RADT) before initiating antibiotics 2
- Bacterial superinfection of the pharynx in infectious mononucleosis is actually uncommon, occurring in less than 3% of cases 1
- The inflamed pharynx and necrotic tonsils characteristic of mono are seldom subject to bacterial superinfection, either initially or during the illness course 1
Second: Determine If Antibiotics Are Truly Needed
- There is no indication for routine antibiotic use when infectious mononucleosis is diagnosed 1
- Only treat with antibiotics if throat culture or RADT confirms Group A beta-hemolytic streptococci 1
- The presence of tonsillar exudates, fever, and cervical adenopathy can occur with mono alone and does not mandate antibiotic therapy 3
Recommended Antibiotic Regimens (When Strep Is Confirmed)
First-Line Options (Avoiding Aminopenicillins)
First-Generation Cephalosporins:
- Cephalexin or cefadroxil for 10 days 2
- These are acceptable alternatives for patients who cannot receive penicillin, and critically, they avoid the ampicillin-mono rash 2
- Cross-reactivity risk with penicillin is less than 3%, making them safe even in most penicillin-allergic patients 4
Macrolides:
- Azithromycin: 12 mg/kg once daily for 5 days (maximum 500 mg/day) in children, or 500 mg on day 1 followed by 250 mg daily for days 2-5 in adults 5
- Erythromycin: standard dosing for 10 days 2
- Macrolides are suitable alternatives that avoid the aminopenicillin-mono interaction 2
Alternative Option
Clindamycin:
- Children: 20-30 mg/kg/day divided in 2-4 doses for 10 days 2
- Adults: 600 mg/day in 2-4 divided doses for 10 days 2
- Particularly effective for difficult-to-eradicate streptococcal infections with only 1% resistance in the United States 6
Critical Pitfall to Avoid
Never use ampicillin or amoxicillin in patients with known or suspected infectious mononucleosis, even if Group A streptococcal pharyngitis is confirmed 1. The mechanism involves a non-allergic interaction between aminopenicillins and the Epstein-Barr virus infection that produces a characteristic maculopapular rash in the vast majority of patients 1. This rash is distinct from true penicillin allergy and occurs specifically with aminopenicillins in the setting of mono.
Treatment Duration and Follow-Up
- Complete a full 10-day course of the chosen antibiotic to achieve maximal pharyngeal eradication of Group A streptococci 2, 7
- Do not perform routine follow-up throat cultures after completing therapy in asymptomatic patients 2, 7
- Patients become non-contagious after 24 hours of appropriate antibiotic therapy 7
When Antibiotics May Not Be Necessary
- If throat culture or RADT is negative for Group A streptococci, withhold antibiotics entirely 2
- The pharyngitis symptoms in mono will resolve spontaneously without antibiotics in the absence of bacterial superinfection 1
- Symptomatic treatment alone is appropriate for mono without documented streptococcal co-infection 1