Cephalexin

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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.

Objectives:

  • 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.

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 pneumoniae.[1] 

  • Cephalexin is indicated for the treatment of 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] 
  • Cephalexin can also be given before and after surgical operations to decrease the risk of surgical site infections, especially in patients with 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, 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 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 alter the binding of cephalexin to their target site.
  • Also, bacteria can synthesize efflux pumps that pump cephalexin outside the bacterial cell.[4]

Pharmacokinetics

Absorption: Rapid in adults; acid-stable, and can be given without regard to foods.

Time of peak plasma concentration: 1 hour

Distribution: Widely distributed in most body fluids

Plasma Protein binding: 10% to 15%

Metabolism: Cephalosporins like cephalexin do not affect hepatic CYP450 enzymes, which drastically limits the potential for drug-drug interactions when administering cephalexin.[5]

Excretion: The majority (90%) of unchanged drugs is excreted in the urine. It is a characteristic that makes it particularly useful in treating urinary tract infections.

Administration

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 also available as 250 mg or 500 mg tablets. The oral suspension is available in 250 mg/5 ml strength. The oral suspension/liquid should be shaken before administration and kept in a refrigerator between doses. For oral dosage forms (capsules or suspension), the following dose is recommended:[6]

  • 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.

Specific Patients Population 

  • Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment.
  • Patient with Renal Impairment: The manufacturer recommends caution during cephalexin therapy in the presence of renal impairment (creatinine clearance < 30 mL/min, with or without dialysis). A dose reduction may be needed based on clinical observation and renal function monitoring. Manufacturer recommendations are listed below. 
    • CrCL ≥ 60 mL/min: No need for`` dose adjustment
    • CrCL 30-59 mL/min: No dose adjustment; maximum daily dose should not exceed 1 gm
    • CrCL 15-29 mL/min:  250 mg every 8 hours or every 12 hours
    • CrCL 5-14 mL/min not yet on dialysis*: 250 mg every 24 hours
    • CrCL 1-4 mL/min not yet on dialysis*: 250 mg every 48 hours or every 60 h
  • Pregnant women: It is considered a pregnancy category B medicine. There are no adequate and well-controlled studies performed on pregnant women. Based on animal studies conducted on mice and rats, there had been no observation of fertility impairments or fetus harm.
  • Pediatric Patients: The safety and efficacy have been established for cephalexin in pediatric patients. Based on this, it is recommended to use a total daily dose of oral cephalexin capsules calculated based on 25 to 50 mg/kg weight for pediatric patients. It should be given for 7 to 14 days in equally divided doses. The maximum dose is 4 gm daily.
  • Breastfeeding Women: The manufacturer recommends caution during cephalexin therapy in nursing mothers as the drug presents in breast milk.[7]
  • Geriatric Patients: No dose adjustment is needed based on the safety and efficacy established for geriatric patients. However, this drug is substantially excreted via the kidney, so that adjustment would be recommended for geriatric patients with impaired renal functions.

Adverse Effects

Abdominal pain, diarrhea, dyspepsia, gastritis, nausea, vomiting, erythema multiforme, genital pruritus, vaginitis, vaginal discharge, candidiasis, thrombocytopenia, neutropenia, eosinophilia, arthralgia, arthropathy, and arthritis have been reported by manufacturers.[1]

In clinical trials, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, cholestatic jaundice, and interstitial nephritis is reported in patients using cephalexin.

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.[8]

Clostridioides difficile associated diarrhea (CDAD) and colitis have been reported in patients taking cephalexin. It can occur at the beginning of cephalexin administration up to three months post-treatment. Older and immunocompromised patients are at higher risk of developing CDAD following long-term antibiotic treatments.[9]

Immunogenic Hemolytic anemia has been reported as a rare occurrence, especially in patients with hypersensitivity reactions to other cephalosporins. Other hypersensitivity reactions reported are skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms.[10] Cephalexin has very few side effects, but one rare side effect is toxic tendinopathy.[11] 

Drug Interactions

  • Metformin: Coadministration of cephalexin with metformin may result in increased plasma concentration and decreased renal clearance of metformin. It is recommended to monitor patients carefully and adjust the dose of metformin when taking cephalexin and metformin concomitantly.
  • Probenecid: Coadministration of cephalexin with probenecid is not recommended as these may lead to inhibition of the renal excretion of cephalexin.

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.[8] 

Cephalexin is also contraindicated in patients who have known hypersensitivity to cephalexin or other medications of the cephalosporin class.

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] 

Additionally, as cephalexin is excreted by kidneys in unchanged form, patients with renal impairment may have prolonged excretion rates of cephalexin.[1][12] Renal function should be monitored in these patients for dose adjustment.

Monitor blood sugar levels when a patient on metformin is administered cephalexin, as there is an increased risk of hypoglycemia.

Cephalosporin, including cephalexin, might cause prolongation in prothrombin time. Monitor prothrombin time especially in patients with malnutrition, renal or hepatic impairment, using the anticoagulation treatment and antibiotics chronically.

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 or overdose include soreness of the oral cavity, pruritus of pregnancy, and gastrointestinal symptoms like nausea, vomiting, epigastric distress, diarrhea, hematuria.[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.[13]

It is recommended to institute general supportive measures in the event of an overdose. However, the beneficial effects of charcoal hemoperfusion, forced diuresis, peritoneal dialysis, and hemodialysis have not been established. Contact local drug poison center for information on the latest protocol to treat cephalexin overdose.

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 risk for adverse effects of the drug without 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.[13] Nurses should inform patients of possible adverse reactions and ways to address if any adverse reactions precipitate. Pharmacists should perform medication reconciliation to verify the dose and drug-drug interactions.

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 recognize the symptoms that may present, including 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, presenting 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.[13]

If the clinical team works together to understand how to recognize these types of adverse drug reactions to cephalexin, they will be able to intervene better and stop drug administration before significant complications occur. Education on these topics allows for a healthcare environment that optimizes patient safety and care quality. 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 F. Herman

Article Editor:

Muhammad F. Hashmi

Updated:

8/18/2022 12:39:38 PM

PubMed Link:

Cephalexin

References

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[3]

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[8]

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[9]

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[10]

Manoharan A,Kot T, Cephalexin-induced haemolytic anaemia. The Medical journal of Australia. 1987 Aug 17     [PubMed PMID: 3657639]

[11]

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

[12]

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]

[13]

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]