Cephalosporins - an overview | Pharmacology Mentor

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)
Third	Ceftriaxone, cefotaxime, ceftazidime, cefixime	Variable, good Strep	Excellent (Enterobacteriaceae, Neisseria), ceftazidime covers Pseudomonas	Meningitis (ceftriaxone, cefotaxime), gonorrhea, UTI, pneumonia, hospital infections
Fourth	Cefepime	Good (Staph, Strep)	Best, covers Pseudomonas, many hospital pathogens	Nosocomial infections, neutropenic fever
Fifth	Ceftaroline	Best (Staph incl. MRSA, Strep)	Moderate (not Pseudomonas)	MRSA, resistant Strep pneumoniae, complicated skin infections

Spectrum Notes:

Enterococci, Listeria, MRSA (except ceftaroline/ceftobiprole), atypicals: Not covered.
Cephamycins (cefoxitin, cefotetan): Unique for significant anaerobic coverage.

III. Pharmacokinetics & Administration

Agent	Route	Bioavailability	CSF Penetration	Elimination	Dose Adjustment Needed?
Cephalexin	Oral	High	Poor	Renal	Yes (renal impairment)
Cefazolin	IV/IM	NA	Poor	Renal	Yes
Cefuroxime	Oral/IV	Moderate	Moderate	Renal	Yes
Ceftriaxone	IV/IM	NA	Good	Biliary	No*
Cefotaxime	IV/IM	NA	Good	Renal	Yes
Cefepime	IV/IM	NA	Good	Renal	Yes
Ceftaroline	IV	NA	Good	Renal	Yes

*Note: No dose adjustment for ceftriaxone in renal impairment except in severe hepatic/renal dysfunction.

IV. Clinical Indications by Generation

Generation	Common Indications
First	Cellulitis, impetigo, UTI, surgical prophylaxis
Second	Otitis media, sinusitis, RTIs, PID, abdominal/pelvic infections
Third	Meningitis, gonorrhea, pneumonia, UTI, pyelonephritis, Lyme disease, sepsis
Fourth	Febrile neutropenia, hospital-acquired pneumonia, serious nosocomial infections
Fifth	MRSA skin/soft tissue infection, resistant Strep pneumoniae pneumonia, CAP/SSTI (FDA-approved)

V. Adverse Effects

Adverse Effect	Mechanism/Agent Notes	Clinical Relevance
Allergic reactions (rash, anaphylaxis)	~1–4% cross-reactivity with penicillins	Avoid in true anaphylaxis history
GI upset, diarrhea	Disruption of normal flora	Most frequent AE
C. difficile colitis	More common with 3rd generation	Report and discontinue
Biliary sludging/kernicterus	Ceftriaxone in neonates	Avoid in neonates
Neurotoxicity (seizures, confusion)	Especially cefepime in renal failure	Adjust dose per renal function
Anticoagulant effect	Cefoperazone, cefotetan (vitamin K antagonism)	Monitor INR/PT

VI. Resistance Mechanisms

Mechanism	Details	Overcome By
β-lactamase (ESBL, AmpC)	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

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.

How to cite this page - Vancouver Style

Mentor, Pharmacology. Pharmacology of Cephalosporin antibiotics. Pharmacology Mentor. Available from: https://pharmacologymentor.com/cephalosporins-an-overview/. Accessed on February 2, 2026 at 15:25.

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Pharmacology of Cephalosporin antibiotics