Continuing Education Activity

Cephalexin is an FDA-approved antibiotic. Cephalexin is a first-generation cephalosporin utilized in the treatment of urinary tract infections, respiratory infections, and other bacterial infections. Both streptococci and staphylococci species can cause these infections. This activity reviews the indications, mechanism of action, contraindications, and adverse effects of cephalexin, helping the healthcare team to use it appropriately for patient care.


  • Identify the mechanism of action of cephalexin.
  • Describe the potential adverse effects of cephalexin.
  • Review the toxicity profile of cephalexin.
  • Explain interprofessional team strategies for improving care coordination and communication to advance cephalexin and improve outcomes.


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 pneumoniae.[1] Cephalexin indications include treating 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 having a cesarean section.[3]

Mechanism of Action

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 maintaining 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]

For oral dosage forms (capsules or suspension), the following dosages are recommended:[5]

  • Adults and children 15 years and older—1000 to 4000 daily in divided doses.
  • Children 1 year of age and older—Dosing is weight-based. The usual dose is 25 to 100 mg/kg daily in divided doses.

The oral suspension/liquid should be shaken before administration and kept in a refrigerator between doses.

Adverse Effects

Cephalexin is known for having very few side effects, but one rare side effect is toxic tendinopathy.[6] 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 only a 1 to 3% incidence of allergic or immunologic reactions to cephalosporins after administration of penicillin.[7]


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.[7] Cephalosporins like cephalexin do not affect hepatic CYP450 enzymes, which drastically limits the potential for drug-drug interactions when administering cephalexin.[8]


Peak serum concentrations of cephalexin are seen approximately one hour after a single dose. The serum half-life is 1 to 2 hours, but this can increase to up to 22 hours in patients with drastically reduced creatinine clearance. Additionally, patients on hemodialysis experience an increased half-life of approximately 4 to 5 hours. Patients should ingest cephalexin on an empty stomach, as food consumption delays the onset of the drug and lowers the peak concentration. Also, consuming food with cephalexin can prolong the time the drug is detectable in the serum.[1]

Cephalexin gets excreted in the kidneys, which is a characteristic that makes it particularly useful in treating urinary tract infections. Additionally, patients with kidney disease may have prolonged excretion rates of cephalexin due to renal malfunction.[1][9][1]


Patients taking cephalexin generally have a relatively low incidence of adverse effects when the drug is administered correctly and safely. Adverse effects associated with toxicity include soreness of the oral cavity, gastrointestinal symptoms, and pruritus of pregnancy.[1] Additionally, the are only a few very rare documented cases of cephalexin inducing a fatal episode of Stevens-Johnson syndrome and toxic epidermal necrolysis.[10]

Enhancing Healthcare Team Outcomes

Interprofessional healthcare teams must be aware of the potential for bacterial resistance to cephalexin. Administering cephalexin to a patient with an infection that harbors cephalexin resistance puts them at potential risk for adverse effects of the drug without the potential for curing the infection; this impedes effective management of the infection and increases the potential for bacterial resistance to the drug.

One of the most critical aspects of the cephalexin administration that healthcare teams need to consider is the potential for drug-induced allergic reactions. The most common manifestations of allergic reactions with cephalexin include urticaria and maculopapular exanthema.[10]

Other major and potentially deadly complications of cephalexin are Stevens-Johnson syndrome and toxic epidermal necrolysis. Although these complications are extremely rare, healthcare professionals need to be able to recognize these complications. In this situation, symptoms that may present include an extensive erythematous rash followed by large areas of epidermal sloughing. In Stevens-Johnson syndrome and toxic epidermal necrolysis, the drug reaction can occur as late as one to three weeks after initiation of drug administration. However, this type of drug reaction can happen sooner than one to three weeks, which may present as conjunctivitis or lesions at mucosal membranes. It can also present with flu-like symptoms. These include, but are not limited to, cough, arthralgias, myalgias, and fever and can progress to massive ulcerations on any surface of the body, multisystem organ failure, and ultimately death. The most important way to prevent these progressions and complications is to stop the administration of cephalexin immediately.[10]

If the interprofessional team understands how to recognize these types of adverse drug reactions to cephalexin, they will be better able to intervene and stop drug administration before significant complications occur. Education on these topics allows for a healthcare environment that optimizes both patient safety and quality of care. Interprofessional management of cephalexin therapy with an interprofessional team that includes clinicians, mid-level practitioners, nurses, and pharmacists, all operating as a cohesive healthcare administration unit, will drive better patient outcomes. [Level 5]

Article Details

Article Author

Timothy Herman

Article Editor:

Muhammad Hashmi


5/17/2021 10:04:05 AM

PubMed Link:




Bailey A,Walker A,Hadley A,James DG, Cephalexin--a new oral antibiotic. Postgraduate medical journal. 1970 Mar;     [PubMed PMID: 4914633]


Derrick CW Jr,Reilly K, The role of cephalexin in the treatment of skin and soft-tissue infections. Postgraduate medical journal. 1983;     [PubMed PMID: 6364089]


Valent AM,DeArmond C,Houston JM,Reddy S,Masters HR,Gold A,Boldt M,DeFranco E,Evans AT,Warshak CR, Effect of Post-Cesarean Delivery Oral Cephalexin and Metronidazole on Surgical Site Infection Among Obese Women: A Randomized Clinical Trial. JAMA. 2017 Sep 19;     [PubMed PMID: 28975304]


Pandey N,Cascella M, Beta Lactam Antibiotics 2019 Jan;     [PubMed PMID: 31424895]


Gwee A,Autmizguine J,Curtis N,Duffull SB, Twice- and Thrice-daily Cephalexin Dosing for Staphylococcus aureus Infections in Children. The Pediatric infectious disease journal. 2020 Jun;     [PubMed PMID: 32412727]


Cohen PR, Cephalexin-associated Achilles Tendonitis: Case Report and Review of Drug-induced Tendinopathy. Cureus. 2018 Dec 27;     [PubMed PMID: 30915263]


Pichichero ME, Cephalosporins can be prescribed safely for penicillin-allergic patients. The Journal of family practice. 2006 Feb;     [PubMed PMID: 16451776]


Thompson JW,Jacobs RF, Adverse effects of newer cephalosporins. An update. Drug safety. 1993 Aug;     [PubMed PMID: 8397890]


Bathini L,Jandoc R,Kuwornu P,McArthur E,Weir MA,Sood MM,Battistella M,Muanda FT,Liu A,Jain AK,Garg AX, Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD. Clinical journal of the American Society of Nephrology : CJASN. 2019 Feb 7;     [PubMed PMID: 30630861]


Hafermann MJ,Barber GR,Dreskin SC,Lindberg GK, Fatal case of cephalexin-induced toxic epidermal necrolysis. SAGE open medical case reports. 2014;     [PubMed PMID: 27489646]