antibacterials for systemic use, second-generation cephalosporins. ATC code:
Pharmacology: Pharmacodynamics: Mechanism of action:
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.
After intramuscular (IM) injection of cefuroxime to normal volunteers, the mean peak serum concentrations ranged from 27 to 35 μg/mL for a 750 mg dose and from 33 to 40 μg/mL for a 1000 mg dose, and were achieved within 30 to 60 minutes after administration. Following intravenous (IV) doses of 750 and 1500 mg, serum concentrations were approximately 50 and 100 μg/mL, respectively, at 15 minutes.
AUC and Cmax
appear to increase linearly with increase in dose over the single dose range of 250 to 1000 mg following IM and IV administration. There was no evidence of accumulation of cefuroxime in the serum from normal volunteers following repeat intravenous administration of 1500 mg doses every 8 hours.
Protein binding has been stated as 33 to 50% depending on the methodology used. The average volume of distribution ranges from 9.3 to 15.8 L/1.73 m2
following IM or IV administration over the dosage range of 250 to 1000 mg. 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 humour. Cefuroxime passes the blood-brain barrier when the meninges are inflamed.
Cefuroxime is not metabolised.
Cefuroxime is excreted by glomerular filtration and tubular secretion. The serum half-life after either intramuscular or intravenous injection is approximately 70 minutes. There is an almost complete recovery (85 to 90%) of unchanged cefuroxime in urine within 24 hours of administration. The majority of the cefuroxime is excreted within the first six hours. The average renal clearance ranges from 114 to 170 mL/min/1.73 m2
following IM or IV administration over the dosage range of 250 to 1000 mg.
Special patient populations:
Gender: No differences in the pharmacokinetics of cefuroxime were observed between males and females following a single IV bolus injection of 1000 mg of cefuroxime as the sodium salt.
Elderly: Following IM or IV administration, the absorption, distribution and excretion of cefuroxime in elderly patients are similar to younger patients with equivalent renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in cefuroxime dose selection, and it may be useful to monitor renal function (see Dosage & Administration).
Paediatrics: The serum half-life of cefuroxime has been shown to be substantially prolonged in neonates according to gestational age. However, in older infants (aged >3 weeks) and in children, the serum half-life of 60 to 90 minutes is similar to that observed in adults.
Renal impairment: Cefuroxime is primarily excreted by the kidneys. As with all such antibiotics, in patients with markedly impaired renal function (i.e. Clcr
<20 mL/minute) it is recommended that the dosage of cefuroxime should be reduced to compensate for its slower excretion (see Dosage & Administration). Cefuroxime is effectively removed by haemodialysis and peritoneal dialysis.
Hepatic impairment: Since cefuroxime is primarily eliminated by the kidney, hepatic dysfunction is not expected to have an effect on the pharmacokinetics of cefuroxime.
PK/PD 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).
Toxicology: Preclinical safety data:
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development. No carcinogenicity studies have been performed; however, there is no evidence to suggest carcinogenic potential.
Gamma glutamyl transpeptidase activity in rat urine is inhibited by various cephalosporins; however, the level of inhibition is less with cefuroxime. This may have significance in the interference in clinical laboratory tests in humans.
Microbiology: 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) extended-spectrum beta-lactamases (ESBLs), and Amp-C enzymes, 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 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 sodium 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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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 known and the utility of the agent 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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the activities of cefuroxime sodium and aminoglycoside antibiotics in combination have been shown to be at least additive with occasional evidence of synergy.