Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium. History and discovery
Groups of researchers at Merck and Lilly discovered Cephamycin C while looking at penicillin-producing bacteria. This followed their discovery of erythromycin, another antibiotic. Cephamycin C was the first cephem discovered but while it was highly resistant to several beta-lactamases, as is its derivative cefoxitin, it was almost only effective against Gram negative bacteria. The scientists used chemically modified the compound to give cefoxitin, so titled due to its semi-synthetic nature. This new modification broadened its spectrum to include Gram positive bacteria. More than 300 modifications were made to it and tested on the cephalosporin base with methoxy groups at the 7-alpha position. Yet only cefoxitin retained its previous effectiveness against Gram negative bacteria, developed effectiveness against Gram positive bacteria, and resisted breakdown by beta-lactamase.Cefoxitin, and the cephamycin family as a whole, served as a branching point and impulsed the discovery of more classes of beta-lactams. This is in part due to their primary and early discovery in the broths studied. Mechanism
Cefoxitin is a beta-lactam antibiotic which binds to penicillin binding proteins, or transpeptidases.
By binding to PBPs, cefoxitin prevents the PBPs from forming the cross-linkages between the peptidoglycan layers that make up the bacterial cell wall, thereby interfering with cell wall synthesis. It is a strong beta-lactamase inducer, as are certain other antibiotics (such as imipenem). However, cefoxitin is a better substrate than imipenem for beta-lactamases. Microbiological resistance
In the presence of cefoxitin, bacteria that make beta-lactamases will increase their production and secretion to cleave the beta lactam ring. As a cephamycin, cefoxitin is highly resistant to hydrolysis by some beta-lactamases, in part due to the presence of the 7-alpha-methoxy functional group (see skeletal formula above).Another more efficient form of resistance to cefoxitin is provided by the mecA gene in bacteria. This gene codes for an alternative penicillin binding protein, PBP2a. This PBP has a lower binding affinity for penicillin-based antibiotics such as cefoxitin and will continue to cross-link the peptidoglycan layers of the cell wall even in the presence of the beta-lactam antibiotics. MRSA, or methicillin-resistant Staphylococcus aureus is a strain that has acquired resistance to cefoxitin via this gene. For the purposes of detecting bacterial strains with the mecC gene, which like mecA codes for a different PBP, cefoxitin is more reliable than oxacillin because mecC does not correlate as strongly with oxacillin resistance. Spectrum of bacterial susceptibility
Cefoxitins spectrum of in vitro antimicrobial activity includes a broad range of gram-negative and gram-positive bacteria, including anaerobes. It is inactive against most strains of Pseudomonas aeruginosa and many strains of Enterobacter cloacae.