Once a licensed physician confirms you have Group A Strep — either through Centor scoring with classic features or through a rapid strep test — the question becomes which antibiotic to prescribe. The good news: Group A Streptococcus has remained universally susceptible to penicillin for the seven decades since the drug was introduced. The IDSA Group A Strep guidelines spell out the algorithm.

First-line: penicillin V or amoxicillin

Penicillin V: 250 mg four times daily or 500 mg twice daily for 10 days. Inhibits bacterial cell wall synthesis. GAS has zero resistance to penicillin globally — a clinical rarity.

Amoxicillin: 500 mg twice daily for 10 days. Equally effective as penicillin V, with the advantage of better palatability (especially for liquid formulations in children) and twice-daily dosing instead of four-times-daily. Increasingly preferred as first-line.

Common side effects: diarrhea, nausea, rash. Severe allergic reactions are rare. Take amoxicillin with or without food.

Penicillin-allergic patients

Non-anaphylactic penicillin allergy: first-generation cephalosporin like cephalexin (Keflex) 500 mg twice daily for 10 days. Cross-reactivity between penicillin and cephalosporins is much lower than once believed (under 1% for second-generation and later).

Severe penicillin allergy (anaphylaxis, Stevens-Johnson, hives): clindamycin 300 mg three times daily for 10 days, or azithromycin (Zithromax) 500 mg day 1 then 250 mg daily for 4 days. Macrolide resistance in GAS is rising in some regions — azithromycin is acceptable but not the first choice if alternatives exist. The CDC's strep throat guidance aligns with this.

Why the full 10 days matters

Symptoms typically improve within 24–48 hours of starting antibiotics, and patients are no longer contagious after 24 hours of appropriate therapy. But the full 10-day course matters — it's not about symptom relief. Completing the course is what prevents acute rheumatic fever, the most serious non-suppurative complication of untreated or under-treated strep. For more on why this matters, see strep complications and why treatment matters.

How CodyMD doctors choose your antibiotic

When you text Cody, the licensed physician considers allergy history (especially penicillin), recent antibiotic exposure, age, pregnancy status, and your specific case. Most adults without allergies receive amoxicillin. Penicillin-allergic patients receive cephalexin (mild allergy) or clindamycin/azithromycin (severe allergy). The doctor will only prescribe if your Centor/McIsaac score and clinical picture support strep — see strep vs viral sore throat for the diagnostic logic.

What's not first-line

Trimethoprim-sulfamethoxazole, tetracyclines, and fluoroquinolones are not appropriate for strep throat — either because of intrinsic resistance, poor tonsillar penetration, or adverse effect profile. And there are no over-the-counter antibiotics in the US — anyone selling "natural antibiotics for strep" is selling something else.

Bottom line

Penicillin V or amoxicillin for 10 days. Cephalexin for non-anaphylactic penicillin allergy. Clindamycin or azithromycin for severe allergy. The right antibiotic depends on you. If you have strep, a CodyMD licensed doctor sends the right one to your pharmacy in 1 hour. For details on how the visit works, see online strep throat treatment.