Ceftaxil-S Mechanism of Action

Pharmacology: Cefotaxime is a third-generation cephalosporin. It has a bacterial action similar to cefamendole, but a broader spectrum of activity. It is highly stable to hydrolysis by most beta-lactamases and has greater activity than first- or second-generation cephalosporins against Gram-negative bacteria. Although cefotaxime is generally considered to have slightly less activity than first-generation cephalosporins against Gram-positive bacteria, many streptococci are very sensitive. Desaceylcefotaxime is an active metabolite of cefotaxime and there may be additive or synergistic effects against some species. Among Gram-negative bacteria, cefotaxime is active in vitro against many Enterobacteriacaea including Citrobacter and Enterobacter spp., Escherichia coli, Klebsiella spp., both indole-positive and indole-negative Proteus, Providencia, Salmonella, Serratia, and Yersinia spp. Other susceptible Gram-negative bacteria, including penicillin-resistant strains are Haemophilus influenza, Moraxella catarrhalis (Branhamella catarrhalis), Neisseria gonorrhoeae, and N. meningitidis. Brucella melitensis is also reported to be moderately sensitive. Some strains of Pseudomonas spp. are moderately susceptible to cefotaxime, but most are resistant. Desacetylcefotaxime is active against many of these Gram-negative bacteria, but not against Pseudomonas spp.
Among Gram-positive bacteria, cefotaxime is active against staphylococci and streptococci. Staphylococcus aureus, including penicillinase-producing strains but not methicillin-resistant Staph. Aureus, is sensitive. Staph. Epidermidis is also sensitive but penicillinase producing strains are resistant. Streptococcus agalactiae (group B streptococci), Str. pneumoniae, and Str. pyogenes (group A streptococci) are all very sensitive although truly penicillin-resistant pneumococci are apparently not sensitive. Enterococci and Listeria monocytogenes are resistant. Cefotaxime is active against some anaerobic bacteria. Bacteroides fragilis may be moderately sensitive, but many strains are resistant; synergy has been demonstrated with desacetlycefotaxime in vitro. Clostridium perfringens is sensitive, but most C. difficile are resistant. Other organisms sensitive to cefotaxime include the spirochaete Borrelia burgdorferi and Haemophilus ducreyi.
The activity of cefotaxime may be enhanced by Aminogycosides.
Pharmacokinetics: Cefotaxime is given by injection as the sodium salt. It is rapidly absorbed after intramuscular injection and mean peak plasma concentrations of about 12 and 20 micrograms/m have been reported 30 minutes after doses of 0.5 and 1 g of cefotaxime, respectively. Immediately after intravenous injection of 0.5, 1, or 2 g of cefotaxime, mean peak plasma concentrations of 38, 102, and 215 micrograms/mL, respectively, has been achieved with concentrations ranging from about 1 to 3 micrograms/mL after 4 hours. The plasma half-life of cefotaxime is about 1 hour and that of the active metabolite desacetylcefotaxime about 1.5 hours; half lives are increased in neonates and in patients with severe renal impairment, especially those of the metabolite and a reduction in dosage may be necessary. The effects of liver disease on clearance of cefotaxime and its metabolite have been variable, but in general dosage adjustment has not been considered necessary. About 40% of cefotaxime is reported to be bound to plasma proteins.