Amoxicillin alternatives: what works instead and when to use them

Amoxicillin is a go-to antibiotic for many infections, but it’s not the only option. Whether you have a penicillin allergy, resistance issues, or side effects, there are clear alternatives that can treat the same conditions—if chosen correctly. Below I list common substitutes, when they fit best, and what to watch for.

Common alternatives and when they’re used

Macrolides (azithromycin, clarithromycin): Good for respiratory infections and some skin infections when someone is allergic to penicillin. Azithromycin is often given as 500 mg once then 250 mg daily for a few days. Watch for stomach upset and rare heart rhythm issues (QT prolongation).

Cephalosporins (cephalexin, cefuroxime): These work for ear infections, sinusitis, UTIs, and skin infections. Cross-reactivity with penicillin is low, but if you had a severe penicillin allergy (anaphylaxis), your doctor may avoid them. Cephalexin is commonly used for skin infections and is generally well tolerated.

Doxycycline: A versatile choice for skin infections, some respiratory bugs, tick-borne illnesses, and acne. Typical adult dosing is 100 mg twice daily. Avoid doxycycline in pregnancy and in most children under 8 because it affects bone and teeth development.

Trimethoprim-sulfamethoxazole (Bactrim): Often used for urinary tract infections and MRSA-related skin infections. It’s effective where penicillins aren’t, but check for allergies and drug interactions (for example, with blood thinners).

Clindamycin: Useful for deeper skin and soft-tissue infections and for people allergic to penicillin. It covers many gram-positive bacteria but raises the risk of C. difficile infection, which can cause severe diarrhea.

Fluoroquinolones (levofloxacin, moxifloxacin): Strong options for some complicated infections, including certain lung and urinary infections. They carry higher risks (tendon injury, nerve damage, QT issues) so doctors reserve them for when safer options aren’t suitable.

How to pick the right alternative

Match the drug to the infection and your health history. Ask your provider these questions: Do I have a documented penicillin allergy or just stomach upset? Has a culture identified the bacteria? Am I pregnant or breastfeeding? Do I take other meds that might interact? These answers guide the safest choice.

One practical tip: if you clearly had anaphylaxis to penicillin, avoid cephalosporins unless a specialist recommends them. For common skin infections where MRSA is a risk, think Bactrim, doxycycline, or clindamycin depending on allergies. For simple ear or sinus infections in kids, cephalosporins like cefdinir or cefuroxime are often used when amoxicillin won’t work.

Don’t self-prescribe. Using the wrong antibiotic can cause side effects, fuel resistance, or miss the real problem. If you need help, talk to a clinician or pharmacist—bring notes on allergies, recent antibiotics, and any test results. That makes choosing the safest, most effective alternative much easier.