Cefudyne Mechanism of Action

Antibacterial (Cephalosporin).
Pharmacology: Pharmacodynamics: Film-coated tablet: Mechanism of action: Cefuroxime axetil undergoes hydrolysis by esterase enzymes to the active antibiotic, cefuroxime.
Cefuroxime inhibits bacterial cell wall synthesis following attachment to penicillin-binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Mechanism of resistance: Bacterial resistance to cefuroxime may be due to one or more of the following mechanisms: hydrolysis by beta-lactamases; including (but not limited to) by extended-spectrum beta-lactamases (ESBLs), and AmpC enzymes that may be induced or stably derepressed in certain aerobic gram-negative bacteria species; reduced affinity of penicillin-binding proteins for cefuroxime; outer membrane impermeability, which restricts access of cefuroxime to penicillin-binding proteins in gram-negative bacteria; bacterial efflux pumps.
Organisms that have acquired resistance to other injectable cephalosporins are expected to be resistant to cefuroxime.
Depending on the mechanism of resistance, organisms with acquired resistance to penicillins may demonstrate reduced susceptibility or resistance to cefuroxime.
Cefuroxime axetil breakpoints: Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows: See Table 1.

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Microbiological susceptibility: The prevalence of acquired 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 the local prevalence of resistance is such that the utility of cefuroxime axetil in at least some types of infections is questionable.
Cefuroxime is usually active against the following microorganisms in vitro. (See Table 2.)

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Powder for Suspension: Cefuroxime is bactericidal and has similar spectrum of antimicrobial action and pattern of resistance to those of cefamandole. It is more resistant to hydrolysis by beta-lactamases than cefamandole, and therefore may be more active against beta-lactamase-producing strains of Haemophilus influenzae and Neisseria gonorrhoeae.
Pharmacokinetics: Film-coated tablet: Absorption: After oral administration, cefuroxime axetil is absorbed from the gastrointestinal tract and rapidly hydrolyzed in the intestinal mucosa and blood to release cefuroxime into the circulation. Optimum absorption occurs when it is administered shortly after a meal.
Following administration of cefuroxime axetil tablets, peak serum levels (2.1 mcg/mL for a 125 mg dose, 4.1 mcg/mL for a 250 mg dose, 7.0 mcg/mL for a 500 mg dose and 13.6 mcg/mL for a 1,000 mg dose) occur approximately 2 to 3 hours after dosing when taken with food. The rate of absorption of cefuroxime from the suspension is reduced compared with the tablets, leading to later, lower peak serum levels and reduced systemic bioavailability (4 to 17% less). Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults and therefore is not substitutable on a milligram-per-milligram basis. The pharmacokinetics of cefuroxime is linear over the oral dosage range of 125 to 1,000 mg. No accumulation of cefuroxime occurred following repeat oral doses of 250 to 500 mg.
Distribution: Protein binding has been stated as 33 to 50% depending on the methodology used. Following a single dose of cefuroxime axetil 500 mg tablet, the apparent volume of distribution was 50 L (CV%=28%). Concentrations of cefuroxime in excess of the minimum inhibitory levels for common pathogens can be achieved in the tonsilla, sinus tissues, bronchial mucosa, bone, pleural fluid, joint fluid, synovial fluid, interstitial fluid, bile, sputum and aqueous humor. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Biotransformation: Cefuroxime is not metabolized.
Elimination: The serum half-life is between 1 and 1.5 hours. Cefuroxime is excreted by glomerular filtration and tubular secretion. The renal clearance is in the region of 125 to 148 mL/min/1.73 m².
Special patient populations: Gender: No differences in the pharmacokinetics of cefuroxime were observed between males and females.
Elderly: No special precaution is necessary in the elderly patients with normal renal function at dosages up to the normal maximum of 1 g per day. Elderly patients are more likely to have decreased renal function; therefore, the dose should be adjusted in accordance with the renal function in the elderly.
Pediatrics: In older infants (aged >3 months) and in children, the pharmacokinetics of cefuroxime are similar to that observed in adults.
There is no clinical trial data available on the use of cefuroxime axetil in children under the age of 3 months.
Renal impairment: Cefuroxime is primarily excreted by the kidneys. Therefore, as with all such antibiotics, in patients with markedly impaired renal function (i.e., Clcr <30 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion. Cefuroxime is effectively removed by dialysis.
Hepatic impairment: There are no data available for patients with hepatic impairment. Since cefuroxime is primarily eliminated by the kidney, the presence of hepatic dysfunction is expected to have no effect on the pharmacokinetics of cefuroxime.
Pharmacokinetic/pharmacodynamic relationship: For cephalosporins, the most important pharmacokinetic-pharmacodynamic index correlating with in vivo efficacy has been shown to be the percentage of the dosing interval (%T) that the unbound concentration remains above the minimum inhibitory concentration (MIC) of cefuroxime for individual target species (i.e., %T>MIC).
Powder for Suspension: Cefuroxime axetil is absorbed from the gastrointestinal tract and is rapidly hydrolyzed in the intestinal mucosa and blood to cefuroxime; absorption is enhanced in the presence of food. Peak plasma concentrations are reported about 2 to 3 hours after an oral dose. Up to 50% of cefuroxime in the circulation is bound to plasma proteins. The plasma half-life is about 70 minutes and is prolonged in patients with renal impairment and in neonates.
Cefuroxime is widely distributed in the body including pleural fluid, sputum, bone, synovial fluid and aqueous humour, but only achieves therapeutic concentrations in the CSF when the meninges are inflamed. It crosses the placenta and has been detected in breast milk.
Cefuroxime is excreted unchanged, by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. Probenecid competes for renal tubular secretion with cefuroxime resulting in higher and more prolonged plasma concentrations of cefuroxime. Small amounts of cefuroxime are excreted in bile. Plasma concentrations are reduced by dialysis.