Cephalexin is an antibiotic that is effective against most gram-positive cocci. Additionally, cephalexin is effective against gram-negative bacteria, particularly E. coli, Proteus mirabilis, and Klebsiella pneumonia.[1] Cephalexin indications include for treatment in acute and chronic urinary tract infections, gonorrhea, upper and lower respiratory tract infections, scarlet fever, beta-lactamase-producing staphylococcal infections, and streptococcal septicemia.[1] Cephalexin is also commonly used in treating streptococcal and staphylococcal skin infections.[2] Additionally, cephalexin can also be given before and following surgical operations to decrease the risk of surgical site infections, especially in patients that are having a cesarean section.[3]

Cephalexin is a first-generation cephalosporin. Cephalexin is a beta-lactam antibiotic, meaning its structure contains a beta-lactam ring. In a bacterial cell, peptidoglycan gives the cell wall mechanical stability. Cephalexin (and other beta-lactam antibiotics) use a beta-lactam ring to inhibit the synthesis of peptidoglycan, which is a critical step in the formation of the bacterial cell wall. Specifically, the beta-lactam binds to penicillin-binding proteins (PBPs), resulting in inhibition of the last phase of peptidoglycan synthesis, which is a transpeptidation reaction required for bacterial peptidoglycan cross-linking. This activity results in the loss of cell viability and eventually leads to bacterial cell autolysis.[4]

Although this mechanism of action inhibits a vital step in the maintenance of the bacterial cell wall, bacteria can potentially acquire resistance to cephalexin, which can occur through various mechanisms. The most common resistance mechanism is a bacterial expression of beta-lactamases, which are enzymes that can degrade beta-lactam antibiotics like cephalexin. Additionally, bacteria can obtain resistance to cephalexin by modifying the penicillin-binding proteins, which alters the binding of cephalexin to their target site. Also, bacteria can synthesize efflux pumps that pump cephalexin outside of the bacterial cell.[4]

Cephalexin is administered orally as either 250 mg or 500 mg capsules. These capsules can be given 1 to 4 times daily, usually administered for seven days. Patients often report cephalexin capsules to have an unpleasant taste. The capsule is also notably large, which may be difficult to swallow. Cephalexin should be given on an empty stomach, as it is absorbed better in this environment.[1]

Cephalexin is known for having very few side effects, but one rare side effect is toxic tendinopathy.[5] Another aspect of the cephalexin administration to keep in mind is the potential for allergic reactions to the drug. A patient can develop an allergy to cephalexin if they have taken penicillin in the past. This situation occurs when a patient takes penicillin, and the immune system generates IgG and/or IgM antibodies that have the potential to bind to cephalexin once ingested orally. The thinking is that approximately 10% of patients with a penicillin allergy also have cross-reactions to cephalosporin antibiotics, but this claim does not have support from the literature. Retrospective studies have suggested that there is a 1 to 3% incidence of allergic or immunologic reactions to cephalosporins after administration of penicillin.[6]

Cephalexin and other cephalosporins are contraindicated in patients with a penicillin allergy, as this poses an increased risk of an allergic reaction to cephalexin and other cephalosporins.[6] Cephalosporins like cephalexin do not affect hepatic CYP450 enzymes, which drastically limits the potential for drug-drug interactions when administering cephalexin.[7]