33564-30-6

Cefoxitin is a second generation cephalosporin antibiotic that has been used to treat a wide range of gram-negative and gram-positive bacteria including anaerobes. It acts by interfering with bacterial cell wall synthesis and has also been shown to induce β-lactamase synthesis.

Solid

Mefoxin,Merck Sharp and Dohme,US,1978

A broad spectrum antibiotic

An antibiotic derived from Cephamycin C.

Cefoxitin sodium can be used as semi-synthetic antibiotic derived from Cephamycin C, possessing high resistance to β-lactamase inactivation.

ChEBI: Cefoxitin sodium is an organic molecular entity.

Benzhydryl 3-carbamoyloxymethyl-7α-hydroxy-7β-(2-thienylacetamido) decephalosporanate, 543 mg, is stirred in 15 ml dry DMSO. Sodium hydride, 24 mg (48 mg of a 50% suspension of NaH in mineral oi1, which has been washed with hexane to remove the oil), is added. When hydrogen evolution has ceased, 126 mg dimethyl sulfate is added. The solution is stirred for one hour at room temperature, diluted with 100 ml benzene and washed six times with water; the last wash is made to pH 8, if necessary, by adding sodium bicarbonate. The solution is dried over MgSO4, filtered and evaporated, leaving benzhydryl 3-carbamoyloxymethyl-7β-(2-thienylacetamido)-7α- methoxydecephalosporanate, which may be purified if desired by chromatography on silica gel, eluting with 25:1 chloroformethyl acetate.
Other methylating agents may be used in place of methyl sulfate, e.g., an equimolar amount of methyl iodide, bromide or chloride, using the same conditions, or methyl trifluoromethylsulfonate or trimethyloxonium trinitrobenzenesulfonate. The solvent in the latter two reagents is dimethyl ether-HMPA 1:1, using a reaction temperature of -20°C warming later to 25°C. In each instance, the benzhydryl 3-carbamoyloxymethyl-7β-(2- thienylacetamido)-7α-methoxydecephalosporanate is obtained.
Benzhydryl 3-carbamoyloxymethyl-7β-(2-thienylacetamido)-7α- methoxydecephalosporanate (300 mg) in 0.5 ml in anisole and 2.5 ml of trifluoroacetic acid is reacted for 15 minutes at 10°C. The resulting mixture is evaporated at reduced pressure and flushed twice with anisole. The residue is dissolved in methylene chloride and extracted with 5% sodium bicarbonate solution. The aqueous solution is adjusted to pH 1.8 with 5% phosphoric acid and extracted with ethyl acetate. The organic solution is dried and evaporated to yield the pure 3-carbamoyloxymethyl-7α-methoxy-7β-(2- thienylacetamido)decephalosporanic acid, MP 165°C to 167°C. This may then be converted to the sodium salt.

Mefoxin (Merck).

Antibiotic

Cefoxitin (Mefoxin) is a semisynthetic derivative obtainedby modification of cephamycin C, a 7α-methoxy-substitutedcephalosporin isolated independently from variousStreptomyces by research groups in Japan and the UnitedStates. Although it is less potent than cephalothin againstGram-positive bacteria and cefamandole against most of theEnterobacteriaceae, cefoxitin is effective against certainstrains of Gram-negative bacilli (e.g., E. coli, K. pneumoniae,Providencia spp., S. marcescens, indole-positiveProteus spp., and Bacteroides spp.) that are resistant to thesecephalosporins. It is also effective against penicillin-resistantS. aureus and N. gonorrhoeae. The activity of cefoxitin and cephamycins, in general,against resistant bacterial strains is because of their resistanceto hydrolysis by β-lactamases conferred by the 7α-methoxylsubstituent. Cefoxitin is a potent competitive inhibitor ofmany β-lactamases. It is also a potent inducer of chromosomallymediated β-lactamases. The temptation to exploit the β-lactamase–inhibiting properties of cefoxitin by combining itwith β-lactamase–labile β-lactam antibiotics should be temperedby the possibility of antagonism. In fact, cefoxitin antagonizesthe action of cefamandole against E. cloacae andthat of carbenicillin against P. aeruginosa. Cefoxitin aloneis essentially ineffective against these organisms.
The pharmacokinetic properties of cefoxitin resemblethose of cefamandole. Because its half-life is relativelyshort, cefoxitin must be administered 3 or 4 times daily.Solutions of the sodium salt intended for parenteral administrationare stable for 24 hours at room temperature and 1week if refrigerated. 7α-Methoxyl substitution stabilizes, tosome extent, the β-lactam to alkaline hydrolysis.The principal role of cefoxitin in therapy seems to be forthe treatment of certain anaerobic and mixed aerobic–anaerobicinfections. It is also used to treat gonorrhea caused byβ-lactamase–producing strains. It is classified as a secondgenerationagent because of its spectrum of activity.

In the United States, there are no cefoxitin products approved for veterinary species, but it has been used clinically in several species when an injectable second generation cephalosporin may be indicated.

[1]. miller ak, celozzi e, kong y, et al. cefoxitin, a semisynthetic cephamycin antibiotic: in vivo evaluation. antimicrob agents chemother. 1974 jan;5(1):33-7.
[2]. jacoby ga. ampc beta-lactamases. clin microbiol rev.2009 jan;22(1):161-82.