Cephalosporins

Snapshot

  • A 55-year-old man is in the medical step-down unit for management of his osteomyelitis. The patient has a past medical history of diabetes that is complicated by peripheral neuropathy and gastroparesis. After obtaining a bone culture he is started on empiric antibiotic treatment with vancomycin and ceftriaxone; however, the patient still has a fever. A bone culture grew Pseudomonas aeruginosa that is sensitive to cefepime; his antibiotics were narrowed. 

Introduction

  • General principle
    • rule of thumb
      • lower generations favor gram-positive coverage
      • higher generations favor gram-negative coverage
        • except for 4th and 5th generation, which has extended gram-positive coverage
  • Drugs
    • 1st generation
      • cefazolin
      • cephalexin
    • 2nd generation
      • cefoxitin
      • cefaclor
      • cefuroxime
    • 3rd generation
      • ceftriaxone
      • cefotaxime
      • ceftazidime
      • cefixime
    • 4th generation
      • cefepime
    • 5th generation
      • ceftaroline
  • Mechanism of action
    • binds to penicillin-binding proteins, inhibiting bacterial cell wall synthesis 
  • Mechanism of resistance
    • altered penicillin-binding proteins
    • production of cephalosporinases
  • Clinical use
    • 1st generation
      • P. mirabilis
      • E. coli
      • K. pneumoniae
      • preventative measure against S. aureus wound infection prior to surgery (cefazolin)
    • 2nd generation
      • H. influenzae
      • Enterobacter aerogenes
      • Neisseria spp.
      • S. marcescens
      • P. mirabilis
      • E. coli
      • K. pneumoniae
    • 3rd generation
      • gram-negative infections
      • meningitis, gonorrhea, and disseminated Lyme disease (ceftriaxone)
      • Pseudomonas (ceftazidime)
    • 4th generation
      • Pseudomonas
    • 5th generation
      • gram-negative and gram-positive organisms
        • does not cover Pseudomonas
  • Adverse events
    • hypersensitivity reaction
    • autoimmune hemolytic anemia
    • disulfiram-like reaction
    • vitamin K deficiency
    • note that there is low cross-reactivity with penicillin (even in penicillin-allergic patients)
    • increased nephrotoxicity with aminoglycosides