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Suprax (cefixime) , given orally, is about 40%-50% absorbed whether administered with or without food; however, time to maximal absorption is increased approximately 0.8 hours when administered with food. The oral suspension produces average peak concentrations approximately 25%-50% higher than the tablets, when tested in normal adult volunteers. Two hundred and 400 mg doses of oral suspension produce average peak concentrations of 3 mcg/mL (range 1 to 4.5 mcg/mL) and 4.6 mcg/mL (range 1.9 to 7.7 mcg/mL), respectively, when tested in normal adult volunteers. The area under the time versus concentration curve is greater by approximately 10%-25% with the oral suspension than with the tablet after doses of 100 to 400 mg, when tested in normal adult volunteers. This increased absorption should be taken into consideration if the oral suspension is to be substituted for the tablet. Because of the lack of bioequivalence, tablets should not be substituted for oral suspension in the treatment of otitis media. (See DOSAGE AND ADMINISTRATION). Cross-over studies of tablet versus suspension have not been performed in children.

Peak serum concentrations occur between 2 and 6 hours following oral administration of 400 mg of Cefixime suspension. Peak serum concentrations occur between 2 and 5 hours following a single administration of 200 mg of suspension.

TABLE

Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours. In animal studies, it was noted that cefixime is also excreted in the bile in excess of 10% of the administered dose. Serum protein binding is concentration independent with a bound fraction of approximately 65%. In a multiple dose study conducted with a research formulation which is less bioavailable than the tablet or suspension, there was little accumulation of drug in serum or urine after dosing for 14 days. The serum half-life of cefixime in healthy subjects is independent of dosage form and averages 3-4 hours but may range up to 9 hours in some normal volunteers. Average AUCs at steady state in elderly patients are approximately 40% higher than average AUCs in other healthy adults.

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.

Standardized procedures require the use of laboratory control organisms. The 5-mcg disk should give the following zone diameter:

The class disk for cephalosporin susceptibility testing (the cephalothin disk) is not appropriate because of spectrum differences with cefixime. The 5-mcg cefixime disk should be used for all in vitro testing of isolates.

Dilution Techniques

Broth or agar dilution methods can be used to determine the minimum inhibitory concentration (MIC) value for susceptibility of bacterial isolates to cefixime. The recommended susceptibility breakpoints are as follows:

As with standard diffusion methods, dilution procedures require the use of laboratory control organisms. Standard cefixime powder should give the following MIC ranges in daily testing of quality control organisms:

Clinical Studies

In clinical trials of otitis media in nearly 400 children between the ages of 6 months to 10 years, Streptococcus pneumoniae was isolated from 47% of the patients, Haemophilus influenzae from 34%, Moraxella (Branhamella) catarrhalis from 15% and S. pyogenes from 4%.

The overall response rate of Streptococcus pneumoniae to cefixime was approximately 10% lower and that of Haemophilus influenzae or Moraxella (Branhamella) catarrhalis approximately 7% higher (12% when beta-lactamase positive strains of H. influenzae are included) than the response rates of these organisms to the active control drugs.

In these studies, patients were randomized and treated with either cefixime at dose regimens of 4 mg/kg BID or 8 mg/kg QD, or with a standard antibiotic regimen. Sixty-nine to 70% of the patients in each group had resolution of signs and symptoms of otitis media when evaluated 2 to 4 weeks post-treatment, but persistent effusion was found in 15% of the patients. When evaluated at the completion of therapy, 17% of patients receiving cefixime and 14% of patients receiving effective comparative drugs (18% including those patients who had Haemophilus influenzae resistant to the control drug and who received the control antibiotic) were considered to be treatment failures. By the 2 to 4 week follow-up, a total of 30%-31% of patients had evidence of either treatment failure or recurrent disease.

REFERENCES

1. Bauer AW, Kirby WMM, Sherris JC, et al.: Antibiotic susceptibility testing by a standard single disk method. Am J Clin Pathol 1966; 45:493.

2. National Committee for Clinical Laboratory Standards, Approved Standard: Performance Standards for Antimicrobial Disk Susceptibility Tests (M2-A3), December 1984.

3. Standardized disk susceptibility test. Federal Register 1974; 39 (May 30): 19182- 19184.

Last reviewed on RxList: 10/11/2010
This monograph has been modified to include the generic and brand name in many instances.