Substitute for Amoxicillin: Common Alternatives and Practical Tips

Need an amoxicillin substitute? Whether it’s an allergy, resistance, or side effects, there are several antibiotics doctors use instead. Which one fits depends on the infection type, your allergies, age, pregnancy status, and local resistance patterns. This page helps you understand common options and why a healthcare pro should pick the right drug.

When you might need a substitute

If you’re allergic to penicillin or haven’t responded to amoxicillin, your doctor will look at the exact infection—ear, sinus, throat, skin, urinary tract, or lungs—and decide. Resistance or recurrent infections also push clinicians to try different classes. Never swap or stop antibiotics without medical advice; that raises resistance and can make infections worse.

Common alternatives and when they’re used

Here are the antibiotics most often chosen instead of amoxicillin and what they’re good for.

Amoxicillin-clavulanate (Augmentin) – A step up when bacteria produce beta-lactamase (an enzyme that destroys amoxicillin). Widely used for sinusitis, certain ear infections, and some dental infections.

Cephalexin (Keflex) – A first-generation cephalosporin. Often used for skin infections and some throat infections. If you have a mild penicillin allergy, some doctors may still use a cephalosporin, but discuss this with your clinician first.

Azithromycin (Z-Pak) or Clarithromycin – Macrolides used for respiratory infections when penicillin is not an option. They’re useful in people with true penicillin allergy, but growing resistance can limit effectiveness for some infections.

Doxycycline – A tetracycline that treats respiratory infections, acne-related infections, and some tick-borne illnesses. Not recommended for young children or pregnant people due to effects on bone and teeth.

Clindamycin – Good for skin and soft tissue infections, and an option for penicillin-allergic patients. It can cause diarrhea and, rarely, C. difficile infection, so it’s used when benefits outweigh risks.

Trimethoprim-sulfamethoxazole (TMP-SMX) – Works well for some urinary and skin infections, including certain MRSA strains. Not ideal for all urinary infections, so lab guidance helps.

Nitrofurantoin or Fosfomycin – Preferred for uncomplicated lower urinary tract infections in many cases. They don’t replace amoxicillin for other infection types.

Fluoroquinolones (like ciprofloxacin) – Reserved for specific cases because of serious side effects and resistance concerns. Used for some complicated UTIs and certain bacterial infections when safer drugs aren’t suitable.

Picking the right substitute means matching the bug and the drug, checking allergies, and considering safety in pregnancy, children, and people with kidney or liver issues. Your provider may order cultures or use local antibiograms (resistance reports) to guide the choice.

Got questions about a prescription change? Ask your doctor or pharmacist. If you have a penicillin allergy, make sure they document exactly what happened—rash, breathing trouble, or other symptoms—so the safest antibiotic is chosen next time.