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Mefoxin

Clinical Pharmacology
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CLINICAL PHARMACOLOGY

Following an intravenous dose of 1 gram, serum concentrations were 110 mcg/mL at 5 minutes, declining to less than 1 mcg/mL at 4 hours. The half-life after an intravenous dose is 41 to 59 minutes. Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Probenecid slows tubular excretion and produces higher serum levels and increases the duration of measurable serum concentrations.

Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile.

In a published study of geriatric patients ranging in age from 64 to 88 years with normal renal function for their age (creatinine clearance ranging from 31.5 to 174.0 mL/min), the half-life for cefoxitin ranged from 51 to 90 minutes, resulting in higher plasma concentrations than in younger adults. These changes were attributed to decreased renal function associated with the aging process.

Microbiology

The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. Cefoxitin has in vitro activity against a wide range of gram-positive and gram-negative organisms. The methoxy group in the 7α position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.

Cefoxitin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms

Staphylococcus aureusa (including penicillinase-producing strains)
Staphylococcus epidermidisa
Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

a
Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin.

Most strains of enterococci, e.g., Enterococcus faecalis, are resistant.

Aerobic gram-negative microorganisms

Escherichia coli
Haemophilus influenzae

Klebsiella
spp. (including K pneumoniae)
Morganella morganii

Neisseria gonorrhoeae
(including penicillinase-producing strains)
Proteus mirabilis

Proteus vulgaris

Providencia
spp. (including Providencia rettgeri)

Anaerobic gram-positive microorganisms

Clostridium spp.
Peptococcus niger

Peptostreptococcus
spp.

Anaerobic gram-negative microorganisms

Bacteroides distasonis
Bacteroides fragilis

Bacteroides ovatus

Bacteroides thetaiotaomicron

Bacteroides
spp.

The following in vitro data are available, but their clinical significance is unknown.

Cefoxitin exhibits in vitro minimum inhibitory concentrations (MIC's) of 8 µg/mL or less for aerobic microorganisms and 16 µg/mL or less for anaerobic microorganisms against most ( ≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefoxitin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-negative microorganisms

Eikenella corrodens [non-β-lactamase producers]
Klebsiella oxytoca

Anaerobic gram-positive microorganisms

Clostridium perfringens

Anaerobic gram-negative microorganisms

Prevotella bivia (formerly Bacteroides bivius)

Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae.

Susceptibility Tests

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cefoxitin powder. The MIC values should be interpreted according to the following criteria:

Brand Name: Mefoxin
Generic Name: Cefoxitin
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