Penicillin and amoxicillin are the first-line antibiotics for strep throat. They’ve been the standard treatment for decades because the bacteria that cause strep (group A Streptococcus) have never developed resistance to them. Most courses last 10 days, and you should start feeling better within a day or two of your first dose.
Why Amoxicillin and Penicillin Come First
Amoxicillin is the most commonly prescribed option, especially for children, because it tastes better in liquid form and can be taken once or twice daily. Penicillin works equally well but is sometimes given as a single injection rather than a 10-day oral course, which can be useful when finishing the full prescription might be difficult.
The reason these two remain the go-to choice is simple: group A Strep bacteria have zero resistance to penicillin-type antibiotics. That’s unusual in an era of growing antibiotic resistance, and it makes the treatment highly reliable. These medications are also inexpensive and cause fewer side effects than the alternatives.
Options If You’re Allergic to Penicillin
If you have a penicillin allergy, your provider will choose from several alternatives based on the type of reaction you’ve had. The CDC lists five options:
- Cephalexin: taken twice daily for 10 days. This is a close relative of penicillin, so it’s only safe if your allergy caused a mild reaction like a rash, not a severe one like throat swelling or anaphylaxis.
- Cefadroxil: taken once daily for 10 days. Same restriction as cephalexin for severe penicillin allergies.
- Clindamycin: taken three times daily for 10 days. Safe for people with any type of penicillin allergy.
- Azithromycin: a 5-day course (the familiar “Z-pack”). Safe for any penicillin allergy type.
- Clarithromycin: taken twice daily for 10 days. Also safe for any penicillin allergy type.
There’s an important caveat with azithromycin and clarithromycin. Both belong to a class called macrolides, and resistance is climbing. Among invasive group A Strep samples tested in 2023, 27% were resistant to macrolides. Clindamycin resistance was similarly high at 26%. That doesn’t mean these drugs won’t work for your sore throat, but it does mean your provider may want to confirm the diagnosis with a test rather than prescribe them empirically.
How Long You Take Them
Most antibiotic courses for strep throat last 10 days. The exception is azithromycin, which runs 5 days because the drug stays active in your tissues longer. Finishing the full course matters even after you feel better. Stopping early doesn’t just risk a relapse of symptoms. It’s the primary way to prevent acute rheumatic fever, a rare but serious inflammatory condition that can damage the heart valves. Adequate treatment of strep pharyngitis is the main defense against this complication.
When You’ll Feel Better
Most people notice significant improvement within one to two days of starting antibiotics. Fever typically breaks first, followed by the sore throat easing up. You’re generally no longer contagious within 12 hours of your first dose. Schools and child care centers typically allow kids to return after that 12-hour window, as long as they’re feeling well enough.
If you’re still feeling just as bad after two or three days on antibiotics, contact your provider. It could mean the infection isn’t responding to the medication, or the original diagnosis may need to be reconsidered.
Getting the Right Diagnosis First
Antibiotics only help if you actually have strep. Most sore throats are caused by viruses, and no antibiotic will touch a viral infection. Symptoms alone aren’t reliable enough to tell the difference. Scoring systems that use clinical signs like fever, swollen tonsils, and the absence of a cough have surprisingly low accuracy, with sensitivity as low as 20% to 45% depending on the cutoff used.
A rapid strep test or throat culture is the standard way to confirm the diagnosis before starting antibiotics. Rapid tests give results in minutes. If the rapid test is negative but suspicion remains high (especially in children), a culture or PCR test can catch cases the rapid test misses. Positive test results mean antibiotics are warranted. A negative result means you likely have a virus, and the best approach is rest, fluids, and over-the-counter pain relief.