Is Keflex (Cephalexin) a Type of Penicillin?
No, Keflex (cephalexin) is not a penicillin—it is a first-generation cephalosporin antibiotic with a distinct chemical structure, though it shares a beta-lactam ring with penicillins. 1
Chemical Structure and Classification
- Cephalexin belongs to the cephalosporin class of antibiotics, not the penicillin class. 1
- The FDA drug label explicitly states that "cephalosporins differ from penicillins in the structure of the bicyclic ring system," though both contain a beta-lactam ring. 1
- Cephalexin has a D-phenylglycyl group at the 7-amino position, which is structurally similar to the side chain found in certain penicillins like amoxicillin and ampicillin (amino-penicillins). 1
Cross-Reactivity Concerns in Penicillin-Allergic Patients
While cephalexin is not a penicillin, the shared side chain structure creates important clinical implications:
Risk Profile
- Cephalexin has a significantly elevated cross-reactivity risk of 12.9% in patients with confirmed penicillin allergy, particularly those allergic to amino-penicillins (amoxicillin, ampicillin). 2
- This cross-reactivity is driven by the identical R1 side chain structure, not the shared beta-lactam ring. 2, 3
- The overall cross-reactivity rate for amino-cephalosporins (including cephalexin) with penicillins is 16.45% (95% CI, 11.07-23.75%). 2
Clinical Recommendations for Penicillin-Allergic Patients
For immediate-type (IgE-mediated) penicillin allergies:
- Patients with suspected immediate-type penicillin allergy should avoid cephalexin regardless of severity or time since reaction. 2, 3
- Only cephalosporins with dissimilar side chains (like cefazolin or ceftriaxone) should be used. 2
- Exception: Patients with non-severe immediate-type reactions occurring >5 years ago may receive cephalexin in a controlled medical setting prepared to manage allergic reactions. 4
For delayed-type (T-cell mediated) penicillin allergies:
- Cephalexin should be avoided in patients with suspected non-severe, delayed-type allergy to amoxicillin, penicillin G, V, or piperacillin. 2, 4
- This applies regardless of time since the index reaction. 3
Safe Alternatives
- Cefazolin is specifically recommended as safe because it does not share side chains with currently available penicillins. 2, 3
- Carbapenems and monobactams (aztreonam) can be administered without prior testing in penicillin-allergic patients, regardless of severity. 2, 3
Common Pitfall to Avoid
The widely quoted 10% cross-allergy risk between all penicillins and cephalosporins is outdated and inaccurate. 5 The actual risk is highly dependent on side chain similarity—cephalexin specifically carries higher risk due to its amino-penicillin-like side chain, while cephalosporins like ceftriaxone, ceftazidime, and cefazolin have negligible cross-reactivity. 2, 5