Which antibiotic is appropriate for streptococcal pharyngitis in a patient taking bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), oxcarbazepine, risperidone, and cyclobenzaprine?

Antibiotic Selection for Strep Throat in a Patient on Biktarvy, Oxcarbazepine, Risperidone, and Cyclobenzaprine

For this patient with confirmed streptococcal pharyngitis, prescribe azithromycin 500 mg orally once daily for 5 days, as it has minimal drug-drug interactions with the patient's current medications and provides effective treatment with strong, moderate-quality evidence. 1, 2

Why Azithromycin is the Optimal Choice for This Patient

The critical issue here is avoiding drug-drug interactions with Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). Bictegravir is metabolized primarily through CYP3A4 and UGT1A1 pathways, and potent inhibitors of both pathways can significantly increase bictegravir exposure (up to 315% with dual inhibition). 3

Drug Interaction Considerations

• Penicillin and amoxicillin (first-line agents) have no significant interactions with any of the patient's medications and would normally be preferred. 1, 2 However, if the patient has a documented penicillin allergy, alternatives must be considered.

• First-generation cephalosporins (cephalexin 500 mg twice daily for 10 days) are the preferred alternative if the patient has a non-immediate penicillin allergy, with strong, high-quality evidence and no significant drug interactions with Biktarvy, oxcarbazepine, risperidone, or cyclobenzaprine. 1, 2

• Azithromycin has minimal drug-drug interactions with Biktarvy and does not significantly affect CYP3A4 or UGT1A1 pathways that metabolize bictegravir. 3 Azithromycin requires only 5 days of treatment (12 mg/kg once daily, maximum 500 mg) due to its prolonged tissue half-life. 1, 2

• Clindamycin (300 mg three times daily for 10 days) is another excellent option with no significant interactions with the patient's medications and only ~1% resistance among Group A Streptococcus in the United States. 1, 2

Treatment Algorithm Based on Penicillin Allergy Status

If NO Penicillin Allergy:

• Prescribe amoxicillin 500 mg orally twice daily for 10 days as first-line therapy with proven efficacy, narrow spectrum, and no drug interactions. 1, 2

If Non-Immediate Penicillin Allergy (delayed rash):

• Prescribe cephalexin 500 mg orally twice daily for 10 days with strong, high-quality evidence and only 0.1% cross-reactivity risk. 1, 2

If Immediate/Anaphylactic Penicillin Allergy:

• Prescribe clindamycin 300 mg orally three times daily for 10 days as the preferred choice with ~1% resistance rate. 1, 2
• Alternative: Azithromycin 500 mg orally once daily for 5 days if compliance with a 10-day regimen is unlikely, though macrolide resistance is 5-8% in the United States. 1, 2

Critical Treatment Duration Requirements

All antibiotics except azithromycin require a full 10-day course to achieve maximal pharyngeal eradication of Group A Streptococcus and prevent acute rheumatic fever. 1, 2 Shortening the course by even a few days results in appreciable increases in treatment failure rates and rheumatic fever risk. 1, 2

Azithromycin is the only exception, requiring just 5 days due to its unique pharmacokinetics and prolonged tissue half-life. 1, 2

Specific Medication Interaction Concerns

• Oxcarbazepine is a moderate CYP3A4 inducer, which could theoretically decrease bictegravir exposure. 3 However, this interaction is already present in the patient's regimen and should be monitored by the HIV provider. Adding azithromycin or clindamycin will not worsen this interaction.

• Risperidone and cyclobenzaprine have no significant interactions with any of the recommended antibiotics for strep throat. 1

• Macrolides (azithromycin, clarithromycin) can cause QT prolongation in a dose-dependent manner, but this is generally not clinically significant with standard 5-day azithromycin courses. 2 Risperidone also carries QT prolongation risk, so monitor for additive effects if using azithromycin.

Common Pitfalls to Avoid

• Do not prescribe trimethoprim-sulfamethoxazole (Bactrim) as it fails to eradicate Group A Streptococcus in 20-25% of cases and is absolutely contraindicated for strep throat. 2, 4

• Do not use cephalosporins in patients with immediate/anaphylactic penicillin reactions due to up to 10% cross-reactivity risk. 1, 2

• Do not shorten antibiotic courses below 10 days (except azithromycin's 5-day regimen) as this dramatically increases treatment failure and rheumatic fever risk. 1, 2

• Do not assume all penicillin-allergic patients need macrolides—first-generation cephalosporins are safe and preferred for non-immediate reactions. 1, 2

Adjunctive Symptomatic Treatment

• Offer acetaminophen or NSAIDs (ibuprofen) for moderate to severe symptoms or high fever with strong, high-quality evidence for reducing pain and inflammation. 1, 2

• Avoid aspirin in children due to Reye syndrome risk. 1, 2

• Corticosteroids are not recommended as adjunctive therapy. 1, 2