Pharmacology: Pharmacodynamics: Mode of action:
Cefuroxime axetil owes its in vivo bactericidal activity to the parent compound cefuroxime. All cephalosporins (β-lactam antibiotics) inhibit cell wall production and are selective inhibitors of peptidoglycan synthesis. The initial step in drug action consists of binding of the drug to cell receptors, called Penicillin-Binding Proteins. After a β-lactam antibiotic has bound to these receptors, the transpeptidation reaction is inhibited and peptidoglycan synthesis is blocked. Bacterial lysis in the end result.
Mechanism of resistance:
Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms: hydrolysis by beta-lactamases. Cefuroxime may be efficiently hydrolysed by certain of the extended-spectrum beta-lactamases (ESBLs) and by the chromosomally-encoded (AmpC) enzyme that may be induced or stably derepressed in certain aerobic gram negative bacterial species; reduced affinity of penicillin-binding proteins for cefuroxime; outer membrane impermeability, which restricts access of cefuroxime to penicillin binding proteins in gram-negative organisms; drug efflux pumps.
Methicillin-resistance staphylococci (MRS) are resistant to all currently available β-lactam antibiotics including cefuroxime.
Penicillin-resistance Streptococcus pneumoniae
are cross-resistant to cephalosporins such as cefuroxime through alteration of penicillin binding proteins.
Beta-lactamase negative, ampicillin resistant (BLNAR) strains of H. influenzae should be considered resistant to cefuroxime despite apparent in vitro susceptibility. Strains of Enterobacteriaceae, in particular Klebsiella spp. and Escherichia coli that produce ESBLs (extended spectrum β-lactamase) may be clinically resistant to therapy with cephalosporins despite apparent in vitro susceptibility and should be considered as resistant.
According to the NCCLS (National Committee on Clinical Laboratory Standards) in 2001 the following breakpoints have been defined for cefuroxime axetil: Enterobacteriaceae
: ≤4 μg/ml susceptible, ≥32 μg/ml resistant;
spp.: ≤4 μg/ml susceptible, ≥32 μg/ml resistant;
spp.: ≤4 μg/ml susceptible, ≥16 μg/ml resistant;
: ≤1 μg/ml susceptible, ≥4 μg/ml resistant.
spp. other than S. pneumoniae: Streptococcal isolates susceptible to penicillin (MIC90 0.12 μg/ml) may be considered susceptible to cefuroxime.
The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. (See table.)
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The oral absorption of Cefuroxime axetil is good. Following oral administration, of Cefuroxime axetil, the drug is absorbed as the 1-(acetyloxy)ethyl ester from gastrointestinal tract and rapidly hydrolyzed to Cefuroxime by nonseptic esterases in the intestinal mucosa and blood.
The apparent volume of distribution of Cefuroxime in healthy adults ranges from 9.3%-15.8L/1.73 m2
In adult, serum or plasma half-life of Cefuroxime following oral administration of commercially available Cefuroxime axetil tablets or oral suspension ranges from 1.2-1.6 hours. In neonates and children, the serum half-life of Cefuroxime is inversely proportional to age. Following oral administration of Cefuroxime axetil of oral suspension in children aged 13 months to 12 years of age, the serum half-life of Cefuroxime averages 1.4-16.1 hours. Cefuroxime is excreted mainly by the kidneys. In patients with renal impairment, the serum half-life of the drug is prolonged and generally ranges from 1.9-16.1 hours, depending on the degree of impairment.