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cephalosporins

PharmacologyImmune systemGastrointestinal systemHepatobiliary systemMusculoskeletal system (bone/joint infections)Central nervous systemGenitourinary system

Summary

Cephalosporins are beta-lactam antibiotics that inhibit bacterial cell wall synthesis by binding penicillin-binding proteins (PBPs) and disrupting transpeptidase cross-linking. They are classified into five generations, with increasing gram-negative coverage and CNS penetration as generations advance, while generally losing some gram-positive coverage (with exceptions like ceftaroline).

Detail

Cephalosporins share the beta-lactam ring structure with penicillins and act by binding PBPs, inhibiting the transpeptidation step of peptidoglycan cross-linking in bacterial cell walls, leading to cell lysis (bactericidal, time-dependent killing). They exhibit partial cross-reactivity with penicillin allergies (~1-10%, more clinically relevant with shared R-group side chains rather than the beta-lactam ring itself).

Generations and coverage: - 1st gen (cefazolin, cephalexin): Good gram-positive (staph, strep) coverage, some gram-negative (PEcK: Proteus, E. coli, Klebsiella). Used for surgical prophylaxis and skin infections. - 2nd gen (cefoxitin, cefuroxime, cefaclor): Extended gram-negative coverage (HEN PEcK: Haemophilus, Enterobacter, Neisseria + PEcK), some anaerobic coverage (cefoxitin, cefotetan) used for intra-abdominal infections. - 3rd gen (ceftriaxone, cefotaxime, ceftazidime): Broad gram-negative coverage, crosses blood-brain barrier (used for meningitis). Ceftazidime covers Pseudomonas. Ceftriaxone used for gonorrhea, meningitis, Lyme disease. - 4th gen (cefepime): Increased gram-negative coverage including Pseudomonas, plus gram-positive coverage; resistant to beta-lactamases. - 5th gen (ceftaroline): Broad-spectrum including MRSA (unique among cephalosporins), but not Pseudomonas.

Mechanism of resistance: Bacterial beta-lactamases hydrolyze the beta-lactam ring; extended-spectrum beta-lactamases (ESBLs) and AmpC enzymes confer resistance to many cephalosporins.

Clinical uses: Surgical prophylaxis, meningitis (3rd gen), gonorrhea/PID (ceftriaxone), Lyme disease, MRSA (ceftaroline only), and mixed infections.

Adverse effects: Hypersensitivity reactions, disulfiram-like reaction with certain agents (cefotetan) when combined with alcohol, vitamin K deficiency/bleeding risk (cefotetan, cefoperazone), and increased risk of C. difficile colitis. Ceftriaxone can cause biliary sludging/pseudolithiasis and kernicterus risk in neonates (displaces bilirubin).

Sources

  • First Aid for the USMLE Step 1
  • Katzung's Basic and Clinical Pharmacology
  • Sanford Guide to Antimicrobial Therapy
  • Goodman & Gilman's The Pharmacological Basis of Therapeutics

Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.

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