23B19: Exam Report

Describe the mechanism of action, dose, pharmacokinetics and pharmacodynamics of ceftriaxone

39% of candidates passed this question.

A structured answer under the headings of mechanism of action, dose, pharmacokinetics and pharmacodynamics worked most effectively for this question.

It was expected that candidates would link the mechanism of action of Ceftriaxone (binds to PBP and inhibits final step in peptidoglycan) to its spectrum of activity. Dosing would also include indications for higher dosing, and consideration of the fact that ceftriaxone is available as an IM administration. Details on hypersensitivity (fever, nephritis, haemolytic anaemia) and consideration of C.diff infection was a main part of its pharmacodynamics.

For pharmacokinetics, a structural approach is recommended, important points included excretion through both kidneys and bile and absence of liver metabolism.

Ceftriaxone

Ceftriaxone

Class

3rd Generation Cephalopsorin

Dose

1g (IV) q12h (start dose)

 

2g (IV) q12h (meningitis)

 

1g (IV) od (maintenance)

Mechanism

Bactericidal

MoA

Binds penicillin binding protein (PBP) on bacterial cell wall → inhibits cell wall synthesis → bactericidal

Good penetration \ useful for Pyelonephritis, BBB – menigitis

Time v Conc

Time > MIC

Post Dose Effect

Short

SPectrum

Covers

Doesnt

G+

  • Streptococcus Pneumoniae
  • Streptococci
  • Staphylococci (some cover)

G-

  • E Coli
  • Hemophilus
  • Klebsiella
  • Pseudomonas
  • Enterococcus
  • ESCAPIMS
  • MRSA
  • Listeria
  • Anaerobes

Indications

  • Severe CAP (with Azithromycin)
  • HAP
  • Abdominal infections (with Metronidazole)

PK

A

IV and IM

D

Distribute widely into most body tissues

PPB 95%

M

Minimal metabolism

E

Renal excretion, some biliary excretion so avoid in neonates

AE

  • Acute Interstitial Nephritis

Monitoring

  • Renal fn
  • LFTs