Can I use Cephalexin (Cephalosporin) if I have an allergy to Augmentin (Amoxicillin-Clavulanate)?

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Last updated: April 27, 2025View editorial policy

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From the Guidelines

If you have an allergy to Augmentin, you can likely use cephalosporins, but it's crucial to consult with your healthcare provider to determine the safest approach based on the nature of your allergy. The risk of cross-reactivity between penicillins and cephalosporins is lower than previously thought, with recent studies suggesting a cross-reactivity rate of around 2-4.8% 1. This means that many patients with a penicillin allergy can safely use cephalosporins. However, if your Augmentin allergy caused a severe reaction, such as anaphylaxis, angioedema, or Stevens-Johnson syndrome, it's essential to exercise caution and consider alternative treatments or undergo proper allergy testing before using cephalosporins.

When evaluating the safety of using cephalosporins, it's essential to consider the following factors:

  • The nature of your allergy: If you experienced a mild rash or gastrointestinal upset, cephalosporins might be safe for you.
  • The severity of your reaction: If you had a severe reaction, it's best to avoid cephalosporins until you've had proper allergy testing.
  • The type of cephalosporin: Third or fourth-generation cephalosporins have less cross-reactivity with penicillins and may be a safer option.

According to the Dutch Working Party on Antibiotic Policy (SWAB) guideline, a systematic clinical approach to estimating the risk of recurrence is essential, including recording a formal allergy history and evaluating the pros and cons of alternative antimicrobial treatments 1. Your healthcare provider can help you navigate this process and determine the best course of treatment for your specific situation.

From the Research

Allergy to Augmentin and Cefalosporin Use

  • Patients with an allergy to Augmentin (amoxicillin-clavulanate) may be concerned about using cefalosporins due to the potential for cross-reactivity.
  • Studies have shown that the cross-reactivity between penicillins and cephalosporins is lower than previously reported, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 2.
  • The use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy 2.

Cross-Reactivity and Side Chains

  • The R1 side chain is responsible for the cross-reactivity between penicillins and cephalosporins, with first-generation cephalosporins having a higher cross-reactivity rate due to shared side chains 3, 2.
  • Later-generation cephalosporins, which have distinct side chains, do not have any skin test cross-reactivity with penicillin/amoxicillin 3.

Diagnosis and Testing

  • Skin testing with amoxicillin and amoxicillin-clavulanate is mandatory in patients with immediate allergy to these drugs, as failure to perform it may result in a false-negative test 4.
  • Patients can react to both amoxicillin and clavulanic acid taken in combination, and simultaneous sensitization to both drugs can occur 5.

Safe Use of Cephalosporins

  • There is ample evidence to allow the safe use of cephalosporins in patients with isolated confirmed penicillin or amoxicillin allergy, as the risk of anaphylaxis is low 3.
  • Avoidance of cephalosporins, when they are the drug of choice in a penicillin-allergic individual, results in significant morbidity that outweighs the low risk of anaphylaxis 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cross-reactivity in β-Lactam Allergy.

The journal of allergy and clinical immunology. In practice, 2018

Research

Patients Taking Amoxicillin-Clavulanic Can Become Simultaneously Sensitized to Both Drugs.

The journal of allergy and clinical immunology. In practice, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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