RiteMED Ceftriaxone Mechanism of Action

Pharmacology: Mechanism of Action: Ceftriaxone kills bacteria by interfering with synthesis of the bacterial cell wall. It binds with high affinity to proteins in the bacterial cell wall thus interfering with the peptidoglycan synthesis. Peptidoglycan is a heteropolymeric structure that provides the cell wall with mechanical stability.
Microbiology: Ceftriaxone is bactericidal against a broad spectrum of bacteria at easily achievable plasma concentrations.
Gram-negative Aerobes: Acinetobacter calcoaceticus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli (including ampicillin-resistant and beta-lactamase producing strains), Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase producing strains), Morganella morganii, Neisseria gonorrhoeae (including penicillinase- and non-penicillinase producing strains), Neisseria meningitides, Proteus mirabilis, Proteus vulgaris, Serratia marcescens.
Ceftriaxone is also active against many strains of Pseudomonas aeruginosa.
NOTE: Many strains of the above organisms that are multiply resistant to other antibiotics, e.g., penicillins, cephalosporins and aminoglycosides, are susceptible to ceftriaxone.
Gram-positive Aerobes: Staphylococcus aureus (Including penicillinase-producing strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Viridans group streptococci.
NOTE: Methicillin-resistant staphylococci are resistant to cephalosporins, including ceftriaxone. Most strains of Group D streptococci and enterococci, e.g., Enterococcus (Streptococcus faecalis, are resistant).
Anaerobes: Bacteroides fragilis, Clostridium species, Peptostreptococcus species.
Gram-negative Aerobes: Citrobacter diversus, Citrobacter freundii, Providencia species (including Providencia rettgeri), Salmonella species (including S. typhi), Shigella species.
Gram-positive Aerobes: Streptococcus agalactiae.
Anaerobes: Bacteroides bivius, Bacteroides melaninogenicus.
Pharmacokinetics: Ceftriaxone demonstrates nonlinear dose-dependent pharmacokinetics because of its protein binding; about 85 to 95% is bound to plasma protein depending on the concentration of ceftriaxone.
Mean peak plasma concentrations of about 40 and 80 micrograms/mL have been reported 2 hours after intramuscular injection of 0.5 and 1 g of ceftriaxone, respectively. The plasma half-life of ceftriaxone is not dependent on the dose and varies between 6 and 9 hours; it may be prolonged in neonates. The half-life does not change appreciably in patients with moderate renal impairment, but it may be prolonged in severe renal impairment especially when there is also hepatic impairment.
Ceftriaxone is widely distributed in body tissues and fluids. It crosses both inflamed and non-inflamed meninges, generally achieving therapeutic concentrations in the CSF. It crosses the placenta and low concentrations have been detected in breast milk. High concentrations are achieved in bile.
About 40 to 65% of a dose of ceftriaxone is excreted unchanged in the urine, principally by glomerular filtration, the remainder is excreted in the bile and is ultimately found in the faeces as unchanged drug and microbiologically inactive compounds.