Clatacef Mechanism of Action

Pharmacotherapeutic group: Beta-lactam antibiotics, cephalosporins. ATC Code: J01D A10.
Pharmacology: Pharmacodynamics: Mode of action: Cefotaxime is a third generation broad spectrum bactericidal cephalosporin antibiotic. The bactericidal properties are due to the inhibitory effect of cefotaxime on bacterial cell wall synthesis.
Mechanisms of resistance: Resistance to Cefotaxime may be due to production of extended-spectrum beta-lactamases that can efficiently hydrolyse the drug, to the induction and/or constitutive expression of AmpC enzymes, to impermeability or to efflux pump mechanisms. More than one of these possible mechanisms may co-exist in a single bacterium.
Pharmacokinetics: Absorption/Distribution: Following IM administration of a single 500 mg or 1 g dose of cefotaxime to healthy volunteers, mean peak serum concentrations of 11.7 and 20.5 mcg/mL, respectively, were attained within 30 minutes and declined with an elimination half-life of approximately 1 hour. There was a dose-dependent increase in serum levels after the IV administration of 500 mg, 1 g, and 2 g of cefotaxime (38.9, 101.7, and 214.4 mcg/mL, respectively) without alteration in the elimination half-life. There is no evidence of accumulation following repetitive IV infusion of 1 g doses every 6 hours for 14 days as there are no alterations of serum or renal clearance. About 60% of the administered dose was recovered from urine during the first 6 hours following the start of the infusion.
Metabolism/Excretion: Approximately 20% to 36% of an IV dose of 14C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15% to 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% to 25%. They lack bactericidal activity.
Infants: A single 50 mg/kg dose of cefotaxime was administered as an IV infusion over a 10- to 15-minute period to 29 newborn infants grouped according to birth weight and age. The mean half-life of cefotaxime in infants with lower birth weights (less than or equal to 1,500 g), regardless of age, was longer (4.6 hours) than the mean half-life (3.4 hours) in infants whose birth weight was greater than 1,500 g. Mean serum clearance was also smaller in the lower birth weight infants. Although the differences in mean half-life values are statistically significant for weight, they are not clinically important. Therefore, base dosage solely on age. It is not necessary to differentiate between premature and normal-gestational age infants. Additionally, no disulfiram-like reactions were reported in a study conducted in 22 healthy volunteers administered cefotaxime and ethanol.
Toxicology: Preclinical safety data: There are no pre-clinical data of relevance to the prescriber that are additional to those included in other sections.