Cefoxitin

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Cefoxitin
Cefoxitin.svg
Systematic (IUPAC) name
(6S,7R)-4-(carbamoyloxymethyl)-7-methoxy-
8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-
1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
Trade names Mefoxin
AHFS/Drugs.com monograph
MedlinePlus a682737
Pregnancy
category
  • B
Routes of
administration
IV
Pharmacokinetic data
Metabolism minimal
Biological half-life 41-59 min
Excretion 85% urine
Identifiers
CAS Registry Number 35607-66-0 YesY
ATC code J01DC01
PubChem CID: 441199
DrugBank DB01331 N
ChemSpider 389981 YesY
UNII 6OEV9DX57Y YesY
KEGG D02345 N
ChEBI CHEBI:209807 N
ChEMBL CHEMBL996 N
Chemical data
Formula C16H17N3O7S2
Molecular mass 427.454 g/mol
 N (what is this?)  (verify)

Cefoxitin is a cephamycin antibiotic developed by Merck & Co., Inc., often grouped with the second−generation cephalosporins. It is sold under the brand name Mefoxin.

Microbiology[edit]

Cefoxitin acts by interfering with cell wall synthesis. Its activity spectrum includes a broad range of gram-negative and gram-positive bacteria including anaerobes. It is inactive in vitro to most strains of Pseudomonas aeruginosa and many strains of Enterobacter cloacae. Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin. [1]

Cefoxitin is considered to be a strong beta-lactamase inducer, as are certain other antibiotics (such as imipenem).[2]

Spectrum of Bacterial Susceptibility[edit]

Cefoxitin has a broad spectrum of activity and has been used in the treatment of skin, bone, respiratory and urinary tract infections. Susceptible bacteria include some Staphylococci, Enterococci, Streptococci, and others. The following represents MIC susceptibility data for a few medically significant microorganisms.

  • Escherichia coli: 0.2 μg/ml - 64 μg/ml
  • Haemophilus influenzae: 0.5 μg/ml - 12.5 μg/ml
  • Streptococcus pneumoniae: 0.2 μg/ml - 1 μg/ml

[3]

Syntheses[edit]

The benzhydryl ester of 7-aminocephalosporanic acid (7-ACA) 2 is prepared by previous tosylation of the amino group of the initial 7-ACA, esterification of the carboxyl group with diphenyldiazomethane, and subsequent removal of the tosyl protection. When reacted with nitrous acid, the product is diazotized, and a subsequent reaction of the resulting compound with triethylammonium azide in DCM and then with bromine azide gives the diphenyl methyl ester of 7-bromo-7-azidocephalosporanic acid (4). Treating this with methanol in the presence of silver borofluoride results in the replacement of the bromine atom, giving the diphenylmethyl ester of 7-methoxy-7-azidocephalosporanic acid (5). The resulting azide is reduced by hydrogen in the presence of a platinum oxide catalyst, forming the diphenyl methyl ester of 7-methoxy-7-aminocephalosporanic acid (6). Acylation of this compound with 2-(2-thienyl)acetylchloride gives the benzyhydryl ester of 7-methoxy-7-[2-(2-thienyl)-acetamido]cephalosporanic acid (7), the ester group of which is hydrolyzed using trifluoroacetic acid and then upon reacting the resulting acid with potassium bicarbonate, it is transformed into the potassium salt (8). The resulting product is then hydrolyzed by the enzyme Citrusi acetylesterase (9). Initial reaction with chlorosulfonyl isocyanate followed with water, the resulting compound is transformed into the desired cefoxitin (11).

References[edit]

  1. ^ Mefoxin Official FDA information at Drugs.com
  2. ^ Phillips I, Shannon K (1993). "Importance of beta-lactamase induction". Eur J Clin Microbiol Infect Dis. 12 Suppl 1: S19–26. PMID 8477758. 
  3. ^ http://www.toku-e.com/Assets/MIC/Cefoxitin.pdf
  4. ^ doi:10.3987/S(S)-1977-01-0719
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