Sign Out
Pharmacology: 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/mL have been reported 30 minutes after doses of 500 mg and 1 g of cefotaxime, respectively. Immediately after intravenous injection of 500 mg, 1 g, or 2 g of cefotaxime, mean peak plasma concentrations of 38, 102, and 215 micrograms/mL, respectively, have 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.
Cefotaxime and desacetylcefotaxime are widely distributed in body tissues and fluids; therapeutic concentrations are achieved in the Cerebro Spinal Fluid particularly when the meninges are inflamed. Cefotaxime crosses the placenta and low concentrations have been detected in breast milk.
Following partial metabolism in the liver to desacetylcefotaxime and inactive metabolites, elimination is mainly by the kidneys and about 40 to 60% of a dose has been recovered unchanged in the urine within 24 hours; a further 20% is excreted as the desacetyl metabolite. Relatively high concentrations of cefotaxime and desacetylcefotaxime are achieved in the bile and about 20% of the dose has been recovered in the faeces.
Probenecid competes for renal tubular secretion with cefotaxime resulting in higher and prolonged plasma concentrations of cefotaxime and its desacetyl metabolite. Cefotaxime and its metabolites are removed by hemodialysis.
When microbiological assays have been used, reported pharmacokinetic values may relate to cefotaxime plus its active metabolite, desacetylcefotaxime.
Microbiology: Antimicrobial Action: Cefotaxime is a third-generation cephalosporin. It has a bactericidal action similar to cefamandole, 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 to it.
Desacetylcefotaxime is an active metabolite of cefotaxime and there may be additive or synergistic effects against some species.
Spectrum of activity: Among Gram-negative bacteria, cefotaxime is active in vitro against many Enterobacteriaceae including Citrobacter and Enterobacter spp., Escherichia coli, Klebsiella spp., both indole-positive and indole-negative Proteus, Providencia, Salmonella, Serratia, Shigella, and Yersinia spp. Other susceptible Gram-negative bacteria, including penicillin-resistant strains, are Haemophilus influenzae, Moraxella catarrhalis (Branhamella catarrhalis), Neisseria gonorrhoeae, and N. meningitides. 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 desacetylcefotaxime in vitro. Clostridium perfringens is sensitive, but most Cl. difficile are resistant.
Other organisms sensitive to cefotaxime include the spirochaete Borrelia burgdorferi and Haemophilus ducreyi.
Activity with other antimicrobials: In addition to possible synergy or additive effects with desacetylcefotaxime, the activity of cefotaxime may be enhanced by aminoglycosides such as gentamicin; synergy has been demonstrated in vitro against Gram-negative bacteria including Pseudomonas aeruginosa. There have also been reports of enhanced activity in vitro with other antibacterials including fosfomycin and ciprofloxacin and variable results with penicillins.
Resistance may develop during treatment with cefotaxime due to derepression of chromosomally mediated beta-lactamases, and has been reported particularly in Enterobacter spp., with multiresistant strains emerging during treatment. This type of resistance has also developed in other bacteria including Citrobacter, Serratia, and Pseudomonas spp. Another mechanism of cefotaxime resistance is the development of plasma-mediated, extended-spectrum beta-lactamases, and this has occurred in Klebsiella spp. and also other Enterobacteriaceae. Resistance in Str. pneumoniae is due to the production of altered penicillin-binding proteins.
