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 aureus1(including penicillinase-producing strains)
Staphylococcus epidermidis1
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
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 mcg/mL or less for aerobic microorganisms and 16 mcg/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-ß-lactamase producers]
Klebsiella oxytoca
Anaerobic gram-positive microorganisms
Clostridium perfringens
Anaerobic gram-negative microorganisms
Prevotella bivia (formerlyBacteroides 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 method(1) (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:
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cefoxitin powder should provide the following MIC values:
Diffusion Techniques:
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure (2) requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg cefoxitin to test the susceptibility of microorganisms to cefoxitin.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-mcg cefoxitin disk should be interpreted according to the following criteria:
Interpretation should be as stated above for results using dilution techniques.
Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cefoxitin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-mcg cefoxitin disk should provide the following zone diameters in these laboratory test quality control strains:
Anaerobic Techniques:
For anaerobic bacteria, the susceptibility to cefoxitin as MIC’s can be determined by standardized test methods (3). The MIC values obtained should be interpreted according to the following criteria:
Interpretation is identical to that stated above for results using dilution techniques.
As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standard cefoxitin powder should provide the following MIC values:
