Augmentin Use in Patients with Keflex Allergy
Patients with a Keflex (cephalexin) allergy should avoid Augmentin (amoxicillin/clavulanate) due to the risk of cross-reactivity between these beta-lactam antibiotics. 1
Understanding Cross-Reactivity Risk
The FDA label for Augmentin clearly states that it is contraindicated in patients with "a history of serious hypersensitivity reactions (e.g., anaphylaxis or Stevens-Johnson syndrome) to amoxicillin, clavulanate or to other beta-lactam antibacterial drugs (e.g., penicillins and cephalosporins)." 1
Cross-reactivity between cephalosporins and penicillins occurs due to similarities in their chemical structure, particularly in the R1 side chains:
- Cephalexin (Keflex) is an aminocephalosporin with a higher risk of cross-reactivity with penicillins
- Cross-reactivity between aminocephalosporins like cephalexin and aminopenicillins (including amoxicillin in Augmentin) is higher than with other cephalosporins 2
- The Dutch Working Party on Antibiotic Policy (SWAB) recommends avoiding penicillins with similar side chains in patients with suspected immediate-type allergy to cephalexin 3
Risk Assessment
The risk of cross-reactivity depends on several factors:
- Aminocephalosporins (like cephalexin/Keflex) have a cross-reactivity rate of approximately 16.45% with penicillins 2
- First-generation cephalosporins (including Keflex) have a higher cross-reactivity with penicillins (odds ratio 4.8) 4
- Patients with confirmed amino-penicillin allergy may have a higher risk of cross-reactivity with cephalexin 5
Alternative Antibiotic Options
For patients with Keflex allergy requiring antibiotic therapy, consider these alternatives:
- Aztreonam - safe alternative with no cross-reactivity with penicillins 2
- Clindamycin - recommended for patients with penicillin allergy 3
- Clarithromycin or azithromycin - suitable alternatives for those with penicillin allergy 3
- Carbapenems - may be considered in clinical settings with appropriate monitoring 2
Special Considerations
- Before initiating any beta-lactam antibiotic, a careful inquiry about previous hypersensitivity reactions is essential 1
- The severity and timing of the previous reaction to Keflex should be considered when evaluating alternative antibiotics
- Patients should be monitored for signs of hypersensitivity during and after antibiotic administration 2
Clinical Pitfalls to Avoid
- Don't assume that all beta-lactam allergies are the same - cross-reactivity varies based on specific drugs and their side chains
- Don't rely on the outdated belief that there is a universal 10% cross-reactivity between penicillins and cephalosporins - this is a myth 6
- Don't overlook the potential for serious reactions - anaphylaxis can occur and may be fatal 1
- Don't forget to document the specific nature of the Keflex allergy to guide future antibiotic decisions
Given the contraindication in the FDA label and the significant cross-reactivity risk between aminocephalosporins like Keflex and aminopenicillins like amoxicillin (in Augmentin), alternative antibiotics should be selected for patients with Keflex allergy to minimize the risk of potentially serious hypersensitivity reactions.