Individual Drug Profiles

Cephalexin: Audio Overview

• Cephalexin

  • Cephalexin 2D

     

  • Cephalexin 3D

     

• Cephalexin introduction

  • Cephalexin is a first-generation β-lactam cephalosporin antibiotic that serves as fundamental agent for treatment of community-acquired infections due to susceptible Gram-positive organisms and select Gram-negative bacteria.

    • The clinical significance of cephalexin lies in its oral bioavailability, favorable safety profile, and use across various patient populations, including children, adults, and pregnant individuals.^2,3,4,5,6  

• Cephalexin Mechanism of Action

  • Cephalexin exerts a bactericidal effect by inhibiting bacterial cell wall synthesis.

  • Bactericidal effects occur as result of acylation of penicillin-binding proteins (PBPs), crucial enzymes in the final transpeptidation step of peptidoglycan synthesis.

    • The transpeptidation step is essential for proper structural framework which provides rigidity and shape to bacterial cell walls.

  • Inhibition of this step prevents the cross-linking of peptidoglycan strands, leading to mechanical instability, cell wall degradation, and ultimately osmotic lysis of the bacterial cell.^2,3,7

• Cephalexin Resistance

  • Bacterial resistance can develop:

    • 1. Through production of β-lactamase enzymes (which hydrolyze the β-lactam ring)

    • 2. Alterations in PBPs reducing drug affinity, or

    • 3. Via efflux mechanisms that expel the antibiotic from bacterial cells.²

• Cephalexin Pharmacokinetics

  • Absorption, Distribution

    • Cephalexin is acid-stable and thus well absorbed orally, with bioavailability approaching 90–100%.

    • Well absorbed after oral administration, cephalexin achieves peak plasma concentration within 1 hour whether or not food is present.

    • The drug is 10–15% protein bound, distributing widely to tissues and fluids such as bone, skin, respiratory secretions, and urine.

      •   Penetration into cerebrospinal fluid is poor, limiting its role in treating meningitis.^2,3,8

  • Metabolism

    • Cephalexin undergoes minimal hepatic metabolism, and more than 90% is excreted unchanged in the urine via glomerular filtration and tubular secretion.

    • As elimination half-life ranges from 0.5 to 2 hours, dosing is every 6–8 hours for optimal therapeutic levels.

    • Because excretion is primarily renal, dose adjustment is essential in patients with renal impairment to prevent accumulation and toxicity.

      • Co-administration with probenecid can prolong plasma levels by inhibiting renal excretion.^2,6,8,9

• Cephalexin Therapeutic Uses^4,5

  • Cephalexin is active against:

    • Most Gram-positive cocci, including:

      • Streptococcus pyogenes and

      • Methicillin-susceptible Staphylococcus aureus (MSSA)

    • And select Gram-negative organisms such as:

      •  Proteus mirabilis

      • Escherichia coli, and

      • Klebsiella pneumoniae.

  • Clinical Uses^5,10

    • Skin and soft tissue infections such as cellulitis, wound infections, and abscesses.

    • Pharyngitis and tonsillitis due to group A streptococci.

    • Urinary tract infections (uncomplicated).

    • Otitis media and sinusitis.

    • Bone and joint infections (less commonly used in the current clinical setting).

    • Bacterial endocarditis prophylaxis in some circumstances for penicillin-allergic individuals.

      • Cephalexin remains a mainstay of oral therapy for mild to moderate community-acquired infections when intravenous agents like cefazolin are unnecessary.¹¹

  • Adverse Reactions

    • Cephalexin is usually well tolerated, with adverse reactions reflecting its β-lactam class profile.

      • Gastrointestinal reactions such as nausea, vomiting, diarrhea, and abdominal pain represent the most frequently encountered adverse effects.

      • Hypersensitivity reactions range from mild rashes and urticaria to severe anaphylaxis in penicillin-allergic individuals, though cross-reactivity risk is ≤10%.

      • Clostridioides difficile-associated diarrhea represents a potentially serious complication of broad-spectrum antibiotic use.^4,12

        • Other possible reactions include eosinophilia, transient hepatic enzyme elevation, and interstitial nephritis, though these are rare.

          • Cephalexin is considered safe during pregnancy and lactation.^4,12

  • Clinical Use Summary

    • Cephalexin offers a reliable oral option bridging outpatient and inpatient antibiotic treatment.

      • Its narrow spectrum against skin flora makes it ideal for de-escalation after empiric intravenous therapy using broader-spectrum drugs.

        • Cephalexin's role remains critical in community settings where susceptibility to first-generation cephalosporins persists—notably against MSSA and streptococcal infections.^5,6

    • Cephalexin lacks activity against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus, and most Pseudomonas species, which confines its role primarily to infections lacking these resistant pathogens.

      • Cephalexin is noted for optimal narrow-spectrum therapy and represents an older but still clinically important antibiotic.^4,5,11