Source: Υπουργείο Υγείας (CY) Publisher: BIAL – Portela & Cª, S.A., À Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal
Pharmacotherapeutic group: 1.1.2.3 – Anti-infectious drugs. Antibacterials. Cephalosporins. 3rd generation cephalosporins
ATC code: J01D D08 cefixime
Cefixime, the only active substance of Tricef, is a bacterial agent belonging to the 3rd generation cephalosporins class.
As a beta-lactam antibiotic, acts by inhibiting bacterial cell wall synthesis. It is therefore a bactericidal antibiotic. Due to the introduction of a carboxymethoxy-imino radical in position 7 of cephemic core, cefixime has a high resistance to inactivation by most of the beta-lactamases produced by gram-positive or gram-negative bacteria. This characteristic translates into a similar activity on susceptible bacteria, whether they are or not beta-lactamases producers.
The time that the plasma concentration of cefixime exceeds the MIC (minimum inhibitory concentration) of the infecting organism has
been shown to best correlate with efficacy in PK/PD studies.
The best therapeutic response is estimated to occur when T> MIC is at least 40-50% of the interval between doses.
Bacterial resistance to cefixime may be due to one or more of the following mechanisms:
More than one of these mechanisms of resistance may co-exist in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express cross-resistance to several or all beta-lactam antibiotics or to antibiotics of other classes.
Values of critical concentrations (breakpoints)
The breakpoints established for cefixime by EUCAST (European Committee on Antimicrobial Susceptibility Testing) in April 2010, are:
The prevalence of acquired resistance may vary geographically and with time. For selected species, local information on resistance is desirable particularly when treating severe infections. Expert advice should be sought when the local prevalence is such that the efficacy of the agent, in some types of infections, is questionable.
Aerobes, Gram positive:
Streptococcus pneumoniae (penicillin-susceptible)
Streptococcus pyogenes
Aerobes, Gram negative:
Escherichia coli%
Haemophilus influenzae
Klebsiella species%
Moraxella catarrhalis
Proteus mirabilis%
Enterobacter species
Clostridium difficile
Bacteroides fragilis
Enterococci
Pseudomonas species
Staphylococcus aureus+
Streptococcus pneumoniae (penicillin-resistant)
% ESLB producing isolates are always resistant
+ Cefixime has poor activity against staphylococci (regardless of susceptibility to methicillin)
The presence of a vinyl radical in position 3 gives cefixime a satisfactory ability to be orally absorbed. In fact, the oral bioavailability of this antibiotic is about 48-50%. The presence of food does not affect the oral absorption of cefixime. Tmax is slightly wider, however the Cmax and AUC24 are not modified.
Repeated therapeutic doses do not cause accumulation in the body, either in adults or in children.
Serum protein binding of cefixime is about 70% and the free fraction diffuses well to various body tissues, except CNS. The antibiotic penetrates well into the maxillary sinuses, middle ear, respiratory tract (including the bronchial secretions), tonsils, prostatic fluid and tissue and other organs.
After a dose of 400 mg, in adults, the concentrations in the tissue of the gallbladder and the bile are approximately 20 and 190 mcg/mL, respectively, 4 to 12 hours after ingestion of the antibiotic. Urinary concentrations are also high.
Cefixime undergoes moderate metabolization in the body, and is essentially excreted, in active form, mainly by the bile, and in appreciable amount (20 to 30% of the absorbed dose) in urine.
The excretion of cefixime is slow, whereby the T1/2 is quite long (about 4 hours), which ensures a good coverage compared to susceptible bacteria in the 24 hours following a single administration of 400 mg in adults or 8 mg/kg in children.
Concentrations in urine and bile are very high, since the elimination takes place through these pathways.
There is a longer half-life, a higher AUC24 and an increased urinary excretion in infants when compared with older children, whose pharmacokinetic parameters are comparable to those of adults.
In elderly patients (65-74 years), Cmax and AUC24 have values slightly higher than in young adults (20 to 32 years). However, these differences do not justify a lower dose for the elderly.
No change was found in Cmax or AUC24 in cirrhotic patients after administration of 200 mg of cefixime, however the time for Cmax and T1/2β are increased, as well as renal clearance. No metabolites were detected in serum or urine.
Although only 20 to 30% of the absorbed dose is excreted in the urine, Cmax and T½ increase, for a given dose, as renal impairment is more severe. Thus, if these increases are not enough to require a dose reduction, for a creatinine clearance greater than 20 mL/min, the same does not happen when creatinine clearance is 20 mL/min or lower. In these latter circumstances Cmax can double and T½ almost tripling and it is then necessary to reduce the dosage by half (usually to 200 mg/day for adults and 4 mg/kg daily for children).
Hemodialysis and peritoneal dialysis removes from blood only small amounts of cefixime, a fact that has no clinical relevance.
The studies conducted in rodents and dogs have shown that cefixime is devoid of toxic effects at single or repeated administrations. There were not detected mutagenic or clastogenic properties. The capacity and reproductive behavior of the tested animals was not altered. In rats and mice at cefixime is not teratogenic.
The long-term carcinogenic effect was not assessed.
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