Ceftrex Mechanism of Action

Pharmacology: Ceftriaxone is a third-generation cephalosporin. It inhibits mucopeptide synthesis in the bacterial cell wall, making it defective and osmotically unstable.
Pharmacokinetics: The pharmacokinetics of ceftriaxone are nonlinear and all basic pharmacokinetic parameters, except the elimination half-life, are dose-dependent if based on total drug concentrations.
Absorption: The maximum plasma concentration after a single IM dose of 1 g is about 81 mg/L and is reached in 2-3 hours after administration. The area under the plasma concentration-time curve after IM administration is equivalent to that after IV administration of an equivalent dose, indicating 100% bioavailability of IM administered ceftriaxone.
Distribution: The volume of distribution of ceftriaxone is 7-12 L. Ceftriaxone has shown excellent tissue and body fluid penetration after a dose of 1-2 g; concentrations well above the minimal inhibitory concentrations of most pathogens responsible for infection are detectable for >24 hours in >60 tissues or body fluids including lung, heart, biliary tract/liver, tonsil, middle ear and nasal mucosa, bone as well as cerebrospinal, pleural, prostatic and synovial fluids. On IV administration, ceftriaxone diffuses rapidly into the interstitial fluid, where bactericidal concentrations against susceptible organisms are maintained for 24 hours.
Protein-Binding: Ceftriaxone is reversibly bound to albumin, and the binding decreases with the increase in concentration, eg from 95% binding at plasma concentrations of <100 mg/L to 85% binding, at 300 mg/L. Owing to the lower albumin content, the proportion of free ceftriaxone in interstitial fluid is correspondingly higher than in plasma.
Penetration into Particular Tissues: Ceftriaxone penetrates the inflamed meninges of neonates, infants, and children. Ceftriaxone concentrations exceeds 1.4 mg/L in the cerebrospinal fluid (CSF) 24 hours after IV injection of CEFTREX in doses of 50-100 mg/kg (neonates and infants, respectively). Peak concentration in CSF is reached about 4 hours after IV injection and gives an average value of 18 mg/L.
Mean CSF levels are 17% of plasma concentrations in patients with bacterial meningitis and 4% in patients with aseptic meningitis. In adult meningitis patients, administration of 50 mg/kg leads within 2-24 hours to CSF concentrations several times higher than the minimum inhibitory concentrations required for the most common meningitis pathogens. Ceftriaxone crosses the placental barrier and is excreted in the breast milk at low concentrations.
Metabolism: Ceftriaxone is not metabolized systemically; but is converted to inactive metabolites by the gut flora.
Elimination: Total plasma clearance is 10-22 mL/min. Renal clearance is 5-12 mL/min. 50-60% of ceftriaxone is excreted unchanged in the urine, while 40-50% is excreted unchanged in the bile. The elimination half-life in adults is about 8 hours.
Special clinical situations: In neonates, urinary recovery accounts for about 70% of the dose. In infants <8 days and in elderly persons >75 years the average elimination half-life is usually 2-3 times that in young adults. In patients with renal or hepatic dysfunction, the pharmacokinetics of ceftriaxone are only minimally altered and the elimination half-life is only slightly increased. If kidney function alone is impaired, biliary elimination of ceftriaxone is increased; if liver function alone is impaired, renal elimination is increased.
Microbiology: Ceftriaxone exerts in vitro activity against a wide range of gram-negative and gram-positive microorganisms. It is highly stable to most β-lactamases, both penicillinases and cephalosporinases of gram-positive and gram-negative bacteria. Ceftriaxone is usually active against the following microorganisms in vitro and in clinical infections (see Indications/Uses): Gram-Positive Aerobes: Staphylococcus aureus (methicillin-sensitive), Staphylococci coagulase-negative, Streptococcus pyogenes (β-hemolytic group A), Streptococcus agalactiae (β-hemolytic group B), β-hemolytic Streptococci (non-group A or B), Streptococcus viridans and Streptococcus pneumoniae.
Note: Methicillin-resistant staphylococci are resistant to cephalosporins, including ceftriaxone. Most strains of Group D streptococci and enterococci, eg, Enterococcus (Streptococcus) faecalis are resistant.
Gram-Negative Aerobes: Acinetobacter lwoffii, Acinetobacter anitratus (mostly A. baumanii)*, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, Alcaligenes-like bacteria, Borrelia burgdorferi, Capnocytophaga sp, Citrobacter diversus (including C. amalonaticus), Citrobacter freundii*, Escherichia coli, Enterobacter aerogenes*, Enterobacter cloacae*, Enterobacter sp (other)*, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae**, Moraxella catarrhalis (formerly Branhamella catarrhalis), Moraxella osloensis, Moraxella sp (other), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri*, Proteus vulgaris, Pseudomonas fluorescens*, Pseudomonas sp (other)*, Providencia rettgeri*, Providencia sp (other), Salmonella typhi, Salmonella sp (nontyphoid), Serratia marcescens*, Serratia sp (other)*, Shigella and Vibrio spp, Yersinia enterocolitica, Yersinia sp (other).
*Some isolates of these species are resistant to ceftriaxone, mainly due to the production of the chromosomally encoded β-lactamase.
**Some isolates of these species are resistant due to the production of extended-spectrum, plasmid-mediated β-lactamase.
Note: Many strains of the previously mentioned organisms that are multiply resistant to other antibiotics, eg, penicillins, cephalosporins, and aminoglycosides, are susceptible to ceftriaxone.
Anaerobic Organisms: Bacteroides (bile-sensitive)*** and Clostridium spp (excluding C. difficile), Fusobacterium nucleatum, Fusobacterium sp (other), Gaffkia anaerobica (formerly Peptococcus), Peptostreptococcus sp.
***Some isolates of these species are resistant to ceftriaxone due to β-lactamase production.
Note: Many strains of β-lactamase-producing Bacteroides sp (notably B. fragilis) are resistant. Clostridium difficile is resistant.