Lecture 3

• 1st Generation Cephalosporins

  • Active against many gram +ve cocci and some gram -ve rods
  • Relatively nontoxic and FDA approved for skin & soft tissue infections, respiratory infections, and UTIs
  • Used in patients who have a history of penicillin allergy
  • Cefazolin penetrates most tissues except CNS; used to treat bone and joint infections and consider the drug of choice for surgical prophylaxis
• 2nd Generation Cephalosporins

  • Active against bacteria inhibited by 1st-generation drugs and have extended gram -ve coverage
  • Cefaclor, cefuroxime, cefonicid, and ceforanide are active against H influenzae but not against anaerobes (serratia & Bacteroides)
  • Cefoxitin and cefotetan are active against anaerobes (serratia & Bacteroides) but are less active against H influenzae
• 3rd Generation Cephalosporins

  • Expanded gram-ve activity compared to 2nd-generation, less effective than 1st and 2nd gen. against gram +ve bacteria
  • Active against enteric gram-ve, H. influenzae & Bacteroides
  • Only ceftazidime and cefoperazone are useful against P. aeruginosa
  • Reserved for very serious infections (e.g., sepsis)
  • Therapy of choice for gram-ve mening
• Characteristics of doxime

  • Gram +ve
  • Gram -ve
  • β-lactamase stability
• DoXime is active against

  • Enteric gram-ve
  • H. influenzae
  • Bacteroides
• Only ceftazidime and cefoperazone are useful against

  • P. aeruginosa
• Use of ceftazidime and cefoperazone

  • Reserved for very serious infections (e.g., sepsis)
• Use of ceftazidime and cefoperazone

  • Therapy of choice for gram-ve meningitis as they achieve sufficient levels in the CSF
• 4th Generation Cephalosporins include

  • Cefepime
  • Cefpirome
  • Cefozopran
• 4th Generation Cephalosporins are active against

  • Gram +ve including MSSA but not MRSA
  • Gram -ve including P. aeruginosa
• 4th Generation Cephalosporins are

  • More resistant to beta-lactamases
  • Penetrates well into CSF (effective in meningitis)
• Use of 4th Generation Cephalosporins

  • Reserved to treat moderate-severe nosocomial pneumonia infections caused by multi-resistant bacteria (e.g., P. aeruginosa, Klebsiella, E. coli)
• 5th Generation Cephalosporins include

  • Ceftaroline IV
• Characteristics of Ceftaroline IV

  • Advanced generation with anti-MRSA activity
  • Broad-spectrum cephalosporin with gram +ve activity similar to 1st gen. and gram -ve activity similar to the 3rd-gen
  • Active against MRSA, PRSP
  • Indicated for the treatment of complicated skin infections and community-acquired pneumonia
  • Important gaps in activity include P. aeruginosa, ESBL-producing Enterobacteriaceae, and Acinetobacter baumannii