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