Amoxicillin vs Ampicillin: Key Differences and When to Use Each

When it comes to treating bacterial infections, amoxicillin, a broad-spectrum penicillin antibiotic commonly prescribed for ear, sinus, and respiratory infections and ampicillin, an older penicillin-class drug used for urinary, respiratory, and gastrointestinal infections are two of the most frequently prescribed options. Both belong to the penicillin family and work by stopping bacteria from building cell walls, but they’re not interchangeable. amoxicillin is better absorbed in the gut, which means it works more reliably when taken by mouth. ampicillin, on the other hand, is often given by injection in hospitals because it doesn’t absorb as well orally—especially if you’ve just eaten.

So why does this matter? If you’ve got a stubborn sinus infection, your doctor is more likely to reach for amoxicillin because it stays in your system longer and reaches higher concentrations in the sinuses. But if you’re dealing with a urinary tract infection caused by certain strains of E. coli or a gastrointestinal bug like salmonella, ampicillin might still be the go-to, especially in clinical settings. Amoxicillin also has a broader range—it works against some strains that ampicillin doesn’t touch, like certain types of H. influenzae and Streptococcus pneumoniae. Ampicillin, however, holds its ground against a few enterococcal infections that amoxicillin struggles with. Both can cause side effects like diarrhea or rash, and if you’re allergic to penicillin, neither is safe. Neither works against viruses, and overusing either contributes to antibiotic resistance.

What you won’t find in most drug labels is how often these two are mixed up by patients—and sometimes even by providers. A lot of people think "it’s all penicillin, so it’s the same." But that’s not true. The difference isn’t just in the name; it’s in how your body handles it, what bugs it kills, and where in your body it works best. If you’ve been prescribed one and your symptoms didn’t improve, it might not be because the infection is resistant—it might just be that the wrong penicillin was chosen. The posts below dive into real-world cases, prescribing trends, and what recent studies say about when each drug still makes sense in today’s medical landscape. You’ll see how these two antibiotics stack up against each other, when newer drugs have replaced them, and what to watch for if you’re on either one.