In subjects with moderate impairment of renal function (20 to 40 mL/min creatinine clearance), the average serum half-life of cefixime is prolonged to 6.4 hours. In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours. The drug is not cleared significantly from the blood by hemodialysis or peritoneal dialysis. However, a study indicated that with doses of 400 mg, patients undergoing hemodialysis have similar blood profiles as subjects with creatinine clearances of 21-60 mL/min. There is no evidence of metabolism of cefixime in vivo.

Adequate data on CSF levels of cefixime are not available.

Microbiology

As with other cephalosporins, bactericidal action of cefixime results from inhibition of cell- wall synthesis. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. Cefixime has been shown to be active against most strains of the following organisms both in vitro and in clinical infections (see INDICATIONS):

Gram-positive Organisms.

Streptococcus pneumoniae,
Streptococcus pyogenes.

Gram-negative Organisms.

Haemophilus influenzae
(beta-lactamase positive and negative strains),
Moraxella (Branhamella) catarrhalis
(most of which are beta-lactamase positive),
Escherichia coli,
Proteus mirabilis,
Neisseria gonorrhoeae
(including penicillinase- and non-penicillinase-producing strains).

Cefixime has been shown to be active in vitro against most strains of the following organisms; however, clinical efficacy has not been established.

Gram-positive Organisms.

Streptococcus agalactiae.

Gram-negative Organisms.

Haemophilus parainfluenzae
(beta-lactamase positive and negative strains),
Proteus vulgaris,
Klebsiella pneumoniae,
Klebsiella oxytoca,
Pasteurella multocida,
Providencia species,
Salmonella species,
Shigella species,
Citrobacter amalonaticus,
Citrobacter diversus,
Serratia marcescens.

Note: Pseudomonas species, strains of group D streptococci (including enterococci), Listeria monocytogenes, most strains of staphylococci (including methicillin-resistant strains) and most strains of Enterobacter are resistant to cefixime. In addition, most strains of Bacteroides fragilis and Clostridia are resistant to cefixime.

Susceptibility Testing
Susceptibility Tests:

Diffusion Techniques

Quantitative methods that require measurement of zone diameters give an estimate of antibiotic susceptibility. One such procedure^1-3 has been recommended for use with disks to test susceptibility to cefixime. Interpretation involves correlation of the diameters obtained in the disk test with minimum inhibitory concentration (MIC) for cefixime.

Reports from the laboratory giving results of the standard single-disk susceptibility test with a 5-mcg cefixime disk should be interpreted according to the following criteria:

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “Moderately Susceptible” indicates that inhibitory concentrations of the antibiotic may well be achieved if high dosage is used or if the infection is confined to tissues and fluids (e.g. urine) in which high antibiotic levels are attained. A report of “Resistant” indicates that achievable concentrations of the antibiotic are unlikely to be inhibitory and other therapy should be selected.

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