Cephalexin

Article Author:
Timothy Herman
Article Editor:
Muhammad Hashmi
Updated:
11/4/2019 10:57:59 AM
PubMed Link:
Cephalexin

Indications

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]

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 is utilized to give 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]

Administration

Cephalexin is administered orally as either 250mg or 500mg capsules. These capsules can be given 1 to 4 times daily, usually administered for 7 days. Cephalexin capsule has been known 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]

Adverse Effects

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]

Contraindications

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]

Monitoring

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]

Toxicity

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, there have been a few very rare cases of cephalexin inducing a fatal episode of Stevens-Johnson syndrome and toxic epidermal necrolysis.[8]

Enhancing Healthcare Team Outcomes

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. Additionally, healthcare providers should be careful about administering cephalexin on an empty stomach so it can be maximally absorbed; this allows for more effective management of the infection and a decreased possibility for bacterial resistance to the drug.

One of the most critical aspects of the cephalexin administration that healthcare teams need to be knowledgeable about is the potential for drug-induced allergic reactions. The most common manifestations of allergic reactions with cephalexin include urticaria and maculopapular exanthema.[8]

Other major and potentially deadly complications of cephalexin are Stevens-Johnson syndrome and toxic epidermal necrolysis. Although these complications are incredibly rare, healthcare professionals need to be able to recognize these complications. Symptoms that may present in this situation include an extensive erythematous rash that is 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. [8]

If healthcare providers and teams understand how to recognize these types of adverse drug reactions to cephalexin, they will be better equipped 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.


References

[1] Bailey A,Walker A,Hadley A,James DG, Cephalexin--a new oral antibiotic. Postgraduate medical journal. 1970 Mar;     [PubMed PMID: 4914633]
[2] 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]
[3] 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]
[4] Pandey N,Cascella M, Beta Lactam Antibiotics 2019 Jan;     [PubMed PMID: 31424895]
[5] Cohen PR, Cephalexin-associated Achilles Tendonitis: Case Report and Review of Drug-induced Tendinopathy. Cureus. 2018 Dec 27;     [PubMed PMID: 30915263]
[6] Pichichero ME, Cephalosporins can be prescribed safely for penicillin-allergic patients. The Journal of family practice. 2006 Feb;     [PubMed PMID: 16451776]
[7] Thompson JW,Jacobs RF, Adverse effects of newer cephalosporins. An update. Drug safety. 1993 Aug;     [PubMed PMID: 8397890]
[8] 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]