questions 1

Cephalosporins

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Topic updated on 07/23/17 6:07am

Introduction
  • Classification
    • antibiotic
      • penicillin-family (β-lactam)
        • cephalosporins
  • Drugs
    • 1st generation
      • cefazolin
      • cephalexin
    • 2nd generation
      • cefoxitin
      • cefaclor
      • cefuroxime
    • 3rd generation
      • ceftriaxone
      • cefotaxime
      • ceftazidime
      • cefixime
    • 4th generation
      • cefepime
    • 5th generation
      • ceftaroline
Mechanism
  • Action 
    • bactericidal
    • see Penicillin 
    • β-lactam ring is less susceptible to penicillinases (β-lactamases)
    • additional R groups allow manipulation to produce multiple drugs
  • Resistance
    • see Penicillin 
    • MRSA is resistant to all cephalosporins
      • via modified penicillin-binding protein (PBP)
    • Enterococci (group D strep) are resistant to all cephalosporins
Uses
  • Rule of thumb
    • lower generations favor Gram-positive coverage
    • higher generations favor Gram-negative coverage
      • except 4th generation which has extended Gram-positive coverage
  • 1st generation
    • Gram-positives
    • some Gram-negatives
      • E. coli
      • Proteus
      • Klebsiella
    • given prophylactically against skin infections
  • 2nd generation
    • Gram-positives
    • more Gram-negatives
      • Haemophilus influenzae
      • Neisseria spp.
      • Serratia marcescens
      • Proteus mirabilis
      • E. coli
      • Klebsiella pneumoniae
      • Enterobacter aerogenes
    • Anaerobes
  • 3rd generation
    • serious Gram-negative infections
      • including Pseudomonas (use ceftazidime)
    • gonorrhea
      • use ceftriaxone 
    • meningitis
      • use ceftriaxone
      • most cephalosporins penetrate BBB
    • pyelonephritis
    • pneumonia
  • 4th generation (cefepime)
    • Pseudomonas
    • improved activity against Gram-positive organisms
  • 5th generation (ceftaroline)
    • broad Gram-positive and Gram-negative coverage
    • covers MRSA (non-inferior to vancomycin)
    • does not cover Pseudomonas or anaerobes
Adverse effects
  • Allergy
    • 5-10% of patients with penicillin allergy are also allergic to cephalosporins
    • IgE mediated
    • rash can appear weeks later
  • nephrotoxicity of aminoglycosides
  • Superinfection
    • e.g. C. difficile
  • MTT side chain (methyl-thio-tetrazole) side chain cephalosporins are associated with specific adverse effects
    • disulfiram (Antabuse)-like reaction with ethanol
      • can interfere with metabolism of alcohol
      • acetaldehyde accumulates
      • results in nausea and vomiting
    • interferes with synthesis of Vitamin K-dependent clotting factors
    • seen with
      • cefamandole
      • cefmetazole
      • cefotetan


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