Is Keflex (cephalexin) a beta-lactam antibiotic?

Is Keflex a Beta-Lactam Antibiotic?

Yes, Keflex (cephalexin) is definitively a beta-lactam antibiotic—specifically, it is a first-generation cephalosporin that contains the characteristic beta-lactam ring structure shared by all cephalosporins and penicillins. 1, 2

Structural Classification

• Cephalexin belongs to the beta-lactam class of antimicrobials, which are characterized by the presence of a beta-lactam ring in their molecular structure 1
• The beta-lactam ring (shown in green in structural diagrams) is the core structural feature that cephalexin shares with penicillins, though the two drug classes differ in their bicyclic ring systems 1
• Cephalexin is specifically classified as a first-generation cephalosporin, distinct from aminopenicillins like amoxicillin or penicillinase-resistant penicillins like cloxacillin 3

Mechanism of Action

• Beta-lactam antibiotics, including cephalexin, exert their antibacterial effect by inhibiting bacterial cell-wall synthesis and producing autolysis 1
• This action occurs through binding to penicillin-binding proteins (PBPs) in the bacterial cell wall 1

Clinical Implications of Beta-Lactam Structure

Cross-Reactivity Considerations

• The FDA label explicitly warns that cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy 2
• However, more recent evidence shows the actual cross-reactivity rate is much lower—approximately 2-4.8% in patients with confirmed penicillin allergy 3
• Cross-reactivity is primarily determined by similarity of the R1 side chain structure, not the beta-lactam ring itself 1
• Cephalexin shares an identical R1 side chain with amoxicillin and ampicillin, which increases the theoretical risk of cross-reactivity between these specific agents 1, 3

Allergy Management

• For patients with a history of non-anaphylactic penicillin allergy, cephalosporins with dissimilar R1 side chains can be administered by direct drug challenge without prior testing 1
• However, because cephalexin shares the R1 side chain with amoxicillin/ampicillin, it falls into the higher cross-reactivity category (16.45% skin test positivity in proven aminopenicillin allergy) 1
• This recommendation does NOT apply to severe delayed reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, drug-induced liver injury, or acute interstitial nephritis 4

Chemical Structure Details

• The FDA label describes cephalexin as 7-(D-α-amino-α-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid, monohydrate 2
• Cephalexin has a D-phenylglycyl group as substituent at the 7-amino position and an unsubstituted methyl group at the 3-position 2
• The compound exists as a zwitterion (containing both basic and acidic groups) with an isoelectric point of approximately 4.5 to 5 2

Antimicrobial Spectrum

• As a beta-lactam antibiotic, cephalexin has an antimicrobial spectrum that includes pathogens most frequently encountered in clinical practice, particularly gram-positive cocci 5
• It is useful for infections of the upper and lower respiratory tract, skin and soft tissue, and genitourinary tract 5
• A significant limitation is that cephalexin has poor activity against Haemophilus influenzae, which reduces its utility in pediatric respiratory infections and some cases of acute exacerbations of chronic bronchitis 6, 7