Cephalosporin antibiotics are beta-lactam antibiotics derived from Cephalosporium acremonium, classified by generations based on their antimicrobial spectra and pharmacokinetic properties. They are among the most utilized antibiotics globally, due to broad efficacy and good safety profile.
I. Mechanism of Action
Cephalosporins bind to bacterial penicillin-binding proteins (PBPs) and inhibit the final transpeptidation step of peptidoglycan synthesis in the cell wall. This disrupts cell wall integrity, causes osmotic lysis, and is bactericidal.
Step
Target
Effect
Transpeptidation
PBPs
Inhibits cell wall crosslinking, resulting in lysis
II. Generations, Spectrum, and Key Examples
Generation
Example Agents
Gram + Coverage
Gram – Coverage
Key Uses
First
Cephalexin, cefazolin
Good (Staph, Strep)
Weak (E. coli, K. pneumoniae, Proteus)
Skin/soft tissue, UTI, surgical prophylaxis
Second
Cefuroxime, cefaclor, cefoxitin, cefotetan
Moderate (Staph, Strep)
Better (H. influenzae, some Enterobacter)
RTIs, otitis, abdominal/pelvic (cefoxitin/cefotetan for anaerobes)
Hydrolyze most cephalosporins; ESBL in Gram-negative bacteria
Carbapenems, new inhibitor combos
Altered PBPs
MRSA, penicillin-resistant S. pneumoniae
Ceftaroline, alternative classes
VII. Clinical Pearls
Monitor for allergies, dose-adjust for renal dysfunction except ceftriaxone.
Ceftriaxone: once daily, excellent CNS and tissue penetration, no renal adjustment needed, high utility in outpatient parenteral regimens.
Ceftazidime, cefepime: preferred for Pseudomonas infections.
Ceftaroline: Option for MRSA, severe skin infections.
Cefoxitin/cefotetan: Used for anaerobic intra-abdominal infections.
References (Vancouver Style)
Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 14th ed. New York: McGraw-Hill; 2022.
Bui T, Cecchini M. Cephalosporins. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Feb 16.
Kanis E et al. Structural Analysis and Protein Binding of Cephalosporins. ACS Pharmacol Transl Sci. 2022;5(12):1322-1334.
MSD Manual. Cephalosporins – Infectious Diseases. 2024 May 9.
Reference
Mentor, Pharmacology. Pharmacology of Cephalosporin antibiotics. Pharmacology Mentor. Available from: https://pharmacologymentor.com/cephalosporins-an-overview/. Accessed on October 7, 2025 at 19:23.
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