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.
Staphylococci that are resistant to methicillin and oxacillin should also be considered clinically resistant to cefoxitin even if they test susceptible by in vitro methods.Major bacterial strains susceptible to cefoxitin include:
methicillin-susceptible Staphylococcus aureus
Streptococcus sp. E. coli
Salmonella sp. Proteus vulgaris
Flavobacterium sp. Klebsiella sp.Major bacteria resistant to cefoxitin include:
methicillin-resistant Staphylococcus aureus
Enterococci
Listeria monocytogenes
Enterobacter sp. Bacteroides sp. Replacement and substitution
In a 2005 study, Fernandes et al. determined that cefoxitin serves as an appropriate replacement for methicillin in determining if some bacteria display methicillin resistance. Likewise, Funsun et al. found in a 2009 study that cefoxitin disk assays correctly identified all 60 mecA-positive Staphylococcus aureus, or MRSA isolates, to be resistant to cefoxitin.Due, in part, to the unavailability of methicillin in the United States, cefoxitin has replaced methicillin for disk diffusion tests, which determine the sensitivity of a bacterial specimen to a given antibiotic. Cefoxitin also yields more accurate results for disk diffusion tests. Interpretive criteria for determining susceptibility to cefoxitin via disk diffusion are greater than or equal to 22mm resulting in a "susceptible" result for Staphylococcus aureus and greater than or equal to 25mm for coagulase-negative staphylococci to be considered susceptible.The following are susceptibility data for several medically significant microorganisms, measured by minimum inhibitory concentration, which is an alternative, liquid medium test for susceptibility. 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

Uses in medicine
Cefoxitin is sold in three major IV doses, 1g, 2g, and 10g.