Can a patient allergic to keflex (cephalexin) and Bactrim (sulfamethoxazole‑trimethoprim) but without a penicillin allergy safely take Augmentin (amoxicillin‑clavulanate)?

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Last updated: February 26, 2026View editorial policy

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Can This Patient Take Augmentin?

Yes, a patient with keflex (cephalexin) and Bactrim allergies can safely take Augmentin (amoxicillin-clavulanate), but ONLY if they have NOT had a previous allergic reaction specifically to amoxicillin or ampicillin. 1

Critical Contraindication You Must Rule Out

Augmentin (amoxicillin) and keflex (cephalexin) share identical R1 side chains, creating significant cross-reactivity risk. 1 This means:

  • If the patient's keflex allergy was an immediate-type reaction (urticaria, angioedema, anaphylaxis occurring within 1-6 hours), you should AVOID amoxicillin/Augmentin regardless of severity or timing of the original reaction. 1
  • The cross-reactivity between cephalexin and amoxicillin is driven by their identical side chain structure, not the beta-lactam ring. 1, 2
  • Patients with positive amoxicillin-IgE have significantly higher rates of cephalexin-IgE positivity (14.00% vs. 2.96%, p<0.01). 3

The Bactrim Allergy is Irrelevant

  • Bactrim (sulfamethoxazole-trimethoprim) is a sulfonamide antibiotic with no structural relationship to beta-lactams like Augmentin. [@General Medicine Knowledge]
  • The sulfa allergy does not increase risk of reactions to Augmentin and should not influence this decision. [@General Medicine Knowledge]

What You Need to Document Before Prescribing

Determine the exact nature of the keflex reaction: 1

  • Immediate-type (within 1-6 hours): urticaria, angioedema, bronchospasm, anaphylaxis → AVOID Augmentin 1
  • Delayed-type (after 1 hour): maculopapular rash, delayed urticaria → Consider alternatives 1
  • Severe delayed reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS) → AVOID all beta-lactams including Augmentin 1

Safe Alternative Options

If you cannot use Augmentin due to the keflex allergy:

  • Cephalosporins with dissimilar side chains (ceftriaxone, ceftazidime) can be used safely regardless of the keflex reaction type or severity. 1, 4
  • Carbapenems can be used in patients with immediate-type cephalexin allergy, regardless of severity or timing. 1
  • Fluoroquinolones or macrolides depending on the clinical indication. [@General Medicine Knowledge]

Common Pitfall to Avoid

Do not assume all cephalosporins are the same. 1 The outdated "10% cross-reactivity" myth between penicillins and cephalosporins has been debunked—cross-reactivity is R1 side chain-dependent, not class-dependent. [@4@, 5] Cephalexin specifically shares the same side chain as amoxicillin/ampicillin, making this a high-risk combination. [@3

References

Guideline

Management of Suspected Cephalexin Reaction

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

International journal of clinical pharmacology and therapeutics, 2011

Research

Use of selected cephalosporins in penicillin-allergic patients: a paradigm shift.

Diagnostic microbiology and infectious disease, 2007

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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