3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.1. Scrap
                  3.1.1.4. Antibiotics
                      3.1.1.4.1. Beta-lactam
 3.1.1.4.1.2. Cephalosporins 

Cephalosporins

[PHW2:

 

Structure

  • All drugs in this class have a beta-lactam ring fused with a hydrothiazine ring

 

Characteristics

  • Broad spectrum
  • Classified into generations
    --> With each generation, Gram-positive cover is maintained but Gram-negative cover is improved
  • Some of the 3rd generation cephalosporin also have some activities against pseudomonas

Pharmacodynamics

Mechanisms of action

  • Same as penicillin
  • Beta-lactam ring is more stable than in penicillin
    --> Less susceptible to beta-lactamase

Side-effects

Hypersensitivity

  • Possible cross-reactivity with other beta-lactams

Others

  • Ceftazidime can cause abnormal liver function test, a false positive Coombs test, and rarely, platelet abnormalities

Pharmacokinetics

  • Distributes widely
  • 3rd generation agents penetrates CSF well
    * Especially when meninges are inflamed
  • All cephalosporins readily cross placenta and can penetrate into joints
  • Protein binding is variable
  • Plasma halflife is short (1 - 1.5 hours)
    * Except for ceftriaxone (5.5 - 11 hours)

Specific examples

Cephalothin

  • 1st generation
  • Excreted mostly unaltered by kidney
    --> Need to decrease dose in renal dysfunction

Cefazolin

  • Cefazolin has essentially the same spectrum as cephalothin
    * But achieves higher blood level (probably due to slower renal elimination)

Cefuroxime

  • 2nd generation
  • 2nd generation cephalosporins as a class are more resistant to beta-lactamase
    --> Greater activity against H. influenzae and Neisseria gonorrhoea
  • Cefuroxime is active against Salmonella, E coli, Klebsiella, and enterobacter
  • Commonly used for surgical prophylaxis during bowel surgery, but lacks sufficient anaerobic cover to be used as sole agent

Cefotaxime

  • 3rd generation
  • 3rd generation cephalosporins as a class have improved Gram-negative activity but activity against some Gram-positive bacteria (e.g. staph aureus) is less than 2nd generation
  • Same Gram-negative spectrum as cefuroxime, but also cover some pseudomonas, acinetobacter, and serratia

Ceftazidime

  • 3rd generation
  • Highly active against pseudomonas
    * Including strains resistant to aminoglycosides
  • Much less effect against staphylococcus

Ceftriaxone

  • 3rd generation
  • Long duration of action
    --> Once daily dosing