indication

Used to treat gonorrhoea, meningitis, and severe infections including infections of the kidney (pyelonephritis) and urinary system. Also used before an operation to prevent infection after surgery.

pharmacology

Cefotaxime is a third generation intravenous cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. Cefotaxime works by inhibiting bacterial cell wall biosynthesis. A positive feature of cefotaxime is that it display a resistance to penicillinases and is useful to treat infections that are resistant to penicillin derivatives.

mechanism of action

The bactericidal activity of cefotaxime results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Cefotaxime shows high affinity for penicillin-binding proteins in the cell wall including PBP Ib and PBP III.

toxicity

Adverse effects following overdosage include nausea, vomiting, epigastric distress, diarrhea, and convulsions. Oral rat LD₅₀ is over 20,000 mg/kg while intravenous rat LD₅₀ is over 7,000 mg/kg.

biotransformation

Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M2 and M3) account for about 20-25%. They lack bactericidal activity.

absorption

Rapidly absorbed following intramuscular injection.

half life

Approximately 1 hour.

route of elimination

Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite.

drug interactions

Amikacin: Increased risk of nephrotoxicity

Gentamicin: Increased risk of nephrotoxicity

Kanamycin: Increased risk of nephrotoxicity

Neomycin: Increased risk of nephrotoxicity

Netilmicin: Increased risk of nephrotoxicity

Probenecid: Probenecid may increase the serum level of cefotaxime.

Streptomycin: Increased risk of nephrotoxicity

Tobramycin: Increased risk of nephrotoxicity