Cephalexin (Keflex®) versus Cefazolin (Kefzol®)

Based on "Antibiotic and Chemotherapy"
written by Roger G. Finch

Difference between Cephalexin and Cefazolin

  • Cefazolin is widely used in surgical prophylaxis, especially in biliary tract, because the drug achieves moderately high concentrations in bile.
  • Cephalexin is available only in oral dosage forms.
  • Cefazolin is available only for parenteral administration.


Cephalexin Cefazolin
• Keflex® • Kefzol®
• Ancef®
Keflex Ancef
Drug class
• Cephalosporin antibiotic, first generation
Dose formulations
• Capsules
• Oral suspension
• Tablets
• Injection
Antimicrobial spectrum
• Both antibiotics have similar antibacterial coverage, and have good activity against many Gram-positive cocci.
• Cefazolin is more active against Staphylococcus aureus3 , Streptococcus spp.4 and H. influenzae5than cephalexin.
FDA-approved indications
• Skin and skin structure infections
• Bone and joint infections
• Acute prostatitis
• Otitis media
• Streptococcal pharyngitis
• Sinusitis
• Cystitis
• Respiratory tract infections
• Urinary tract infections
• Biliary tract infections
• Septicemia
• Endocarditis
• Perioperative prophylaxis
"Off-label" uses
• Infective endocarditis (prophylaxis)
• Appendicular peritonitis • Prevention of Group B Streptococcal in newborns (maternal use)1
• Parotitis2
Mechanism of action
• Bactericidal.
• Cephalosporins inhibit the synthesis of bacterial cell walls at the later stages through inactivation of penicillin-binding proteins.
• 0.5 to 1.2 hours • 1.8 hours
Oral bioavailability
• 90% • Cefazolin is not appreciably absorbed from gastrointestinal tract.
Metabolism, Elimination
• Cephalexin is minimally metabolized.
• Cephalexin is eliminated in urine (80% to 100% as unchanged drug).
• Cefazolin is not metabolized in the liver.
• Cefazolin is excreted almost entirely unchanged by the kidneys (about 80% of the drug is eliminated within 24 hours.).
• Hypersensitivity to any cephalosporin antibiotic
Side effects
• Diarrhea
• Nausea
• Vomiting
• Upset stomach
• Abdominal pain
• Allergic reactions
• Nausea
• Vomiting
• Diarrhea
• Allergic reactions

Cephalexin vs Cefazolin for Skin and soft tissue infections


Results of comparative trial of cefazolin versus cephalexin for the treatment of skin and soft tissue infections6 Cephalexin Cefazolin
Dosage regimen 500 mg 4 times daily for up to 7 days 2 g IV daily plus probenecid 1 g daily for up to 7 days
The proportion of patients failing antibiotic treatment at 72 hours 4.2% 6.1%
Clinical cure at 7 days 100% 97.7%
Cephalexin may provide an effective and non-inferior alternative to parenteral cefazolin in the treatment of uncomplicated skin and soft tissue infection.


Further reading


  • 1. Apgar BS, Greenberg G, Yen G. Prevention of group B streptococcal disease in the newborn. Am Fam Physician. 2005 Mar 1;71(5):903-10. Available at AAFP
  • 2. Wissam Sabbagh. Parotitis: Infectious Disease and Antimicrobial Agents AntiMicrobe
  • 3. Hsieh WC, Ho SW. Evaluation of antibacterial activities of cephalosporin antibiotics: cefazolin, cephaloridine, cephalothin, and cephalexin. Zhonghua Min Guo Wei Sheng Wu Xue Za Zhi. 1975 Mar;8(1):1-11.
  • 4. Gupta BL, Tahlan A, Dogra V, Rattan A, Bhujwala RA, Shriniwas. Susceptibility of clinical isolates to cephalexin, cefazolin and cefotaxime. Indian Pediatr. 1989 May;26(5):466-71.
  • 5. Yourassowsky E, Schoutens E. In vitro bacteriostatic and bactericidal activities of 7 cephalosporin antibiotics on Haemophilus influenzae. Int J Clin Pharmacol Biopharm. 1975 Dec;12(4):433-6.
  • 6. Dalen D, Fry A, Campbell SG, Eppler J, Zed PJ. Intravenous cefazolin plus oral probenecid versus oral cephalexin for the treatment of skin and soft tissue infections: a double-blind, non-inferiority, randomised controlled trial. Emerg Med J. 2018 Aug;35(8):492-498.
  • 7. Keflex® Prescribing Information PDF
  • 8. Ancef® Prescribing Information PDF

Published: August 28, 2018
Last reviewed: August 28, 2018


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