Amoxicillin vs Cephalexin

Amoxicillin is the preferred antibiotic for strep throat (group A streptococcal pharyngitis) per IDSA guidelines, and is first-line for acute otitis media (ear infections), acute bacterial sinusitis, and many dental infections. It has excellent oral absorption and achieves good tissue concentrations.

Cephalexin is preferred for uncomplicated skin and soft tissue infections (cellulitis, impetigo) caused by susceptible staphylococcal and streptococcal organisms. It is also commonly used for uncomplicated UTIs and prophylaxis before certain procedures.

Both antibiotics are ineffective against MRSA, atypical organisms (like Mycoplasma), and most gram-negative bacteria except some urinary pathogens. When broader coverage is needed, different antibiotics are required.

Both amoxicillin and cephalexin are generally well tolerated antibiotics. The most common side effects for both are GI-related: diarrhea, nausea, and stomach upset.

Amoxicillin has a higher rate of skin rash, particularly the well-known amoxicillin rash that occurs in patients with infectious mononucleosis (EBV) — this is not a true allergy but can be confused with one. True penicillin allergy (affecting about 1-2% of the population, though reported much more often) rules out amoxicillin use.

Cephalexin carries a question of cross-reactivity in penicillin-allergic patients. Current evidence shows the cross-allergy rate between penicillins and first-generation cephalosporins is low (1-2%), and many allergists now consider cephalexin safe for most patients with non-severe penicillin allergy. However, patients with a history of anaphylaxis to penicillin should still avoid cephalosporins unless evaluated by an allergist.

Both antibiotics have a low risk of C. difficile infection compared to broader-spectrum antibiotics.

Both amoxicillin and cephalexin are available as very affordable generics. Amoxicillin costs approximately $4-$10 for a full course. Cephalexin costs approximately $8-$20 for a full course. Both are available on $4 generic lists at major pharmacies and are covered by all insurance plans.

Amoxicillin is typically taken 2-3 times daily. For strep throat, a once-daily regimen of amoxicillin (high-dose, 50 mg/kg) is also used in children. It is available as capsules, chewable tablets, and a liquid suspension for children.

Cephalexin is taken 2-4 times daily depending on the infection type. It is also available as capsules and liquid suspension. Both antibiotics can be taken with or without food, though taking with food may reduce stomach upset.

The choice between amoxicillin and cephalexin depends primarily on the type of infection. For strep throat, ear infections, and sinusitis, amoxicillin is the standard first-line choice. For skin infections like cellulitis and simple wound infections, cephalexin is typically preferred.

If you have a penicillin allergy, cephalexin may be an option depending on the type of reaction you had — discuss this with your doctor or allergist. If you have a cephalosporin allergy, amoxicillin may still be safe, as cross-reactivity in this direction is very rare.

Always take the full course of antibiotics as prescribed, even if you feel better before finishing.