Pharm 101: Ceftriaxone

Class

Third generation cephalosporin
Other third generation cephalosporins: cefotaxime, ceftazidime, cefoperazone

Pharmacodynamics

• Beta lactam antibiotic
• Inhibits transpeptidation reaction of bacterial cell wall synthesis
• Halts peptidoglycan synthesis, leading to inhibition of bacterial growth, and ultimately cell death (bacteriocidal)
• Beta-lactam antibiotics kill bacterial cells only when they are actively growing and synthesising cell wall

Pharmacokinetics

• IV administration
• Crosses the blood-brain barrier
• Half-life 7-8 hours, allowing once daily administration 15-50mg/kg
• Mixed clearance with biliary excretion, therefore no dose adjustment required in renal failure

Antimicrobial activity

• Expanded gram negative coverage
• Less active against Staph than first/second generation cephalosporins
• Not usually degraded by bacterial beta-lactamases, therefore broader spectrum of activity
• Effective against:
  • Beta lactamase producing strains of Haemophilus and Neisseria
  • Penicillin-resistant pneumococcus
  • Citrobacter
• Not effective against:
  • Enterobacter
  • Pseudomonas
  • L monocytogenes

Adverse effects of cephalosporins

• Allergy:
  • Cross-allergenicity between penicillins and cephalosporins is ~1%
• Toxicity:
  • Thrombophlebitis after IVI
  • Renal toxicity: interstitial nephritis, tubular necrosis (rare)
• Methylthiotetrazole-containing agents (cefotetan, cefoperazone) may cause bleeding disorders and disulfiram-like reactions

Precautions/contraindications

• Penicillin anaphylaxis
• Drug interactions:
  • Warfarin: eliminate bacteria that produce Vitamin K and thus can increase INR

Further reading

• Buttner R. Pharm 101: Cephazolin. LITFL
• Buttner R. Pharm 101: Cefuroxime. LITFL
• Buttner R. Pharm 101: Cefepime. LITFL

References

• Katzung BG. Basic and Clinical Pharmacology. 14e. 2018: 802-806, 812