Structural class and overview

• Cefoxitin is a parenteral cephamycin typically grouped with second-generation cephalosporins.^2,3 

  • Cefoxitin is derived from cephamycin C and is characterized by a 7-α-methoxy group on the β-lactam ring, which confers enhanced stability against many plasmid-encoded β-lactamases and explains much of its anaerobic and Gram-negative activity.

  • Attribution Cefoxitin is the cefamycin antibiotic often grouped with the second-generation cephalosporins. Cefoxitin is composed of the beta-lactam ring (pink) fused to a six-membered dihydrothiazine ring (orange), characteristic of all cephalosporin antibiotics. Other cefoxitin features contributing to its anti-bacterial properties include the 7α methoxy group making cefoxitin a poor substrate for beta-lactamases. PDB-101: Educational resources supporting molecular explorations through biology and medicine.  PDB_101 (PDB101.rcsb.org) (2022) Protein Science 31: 129-140 10.1002/pro.4200 https://pdb101.rcsb.org/global-health/antimicrobial-resistance/drugs/antibiotics/cell-wall-biosynthesis/penicillin-binding-protein/beta-lactams/cefoxitin/cefoxitin

   

  • Microbiological Characterization

    • Cefoxitin exhibits broad gram-negative in anaerobic activity, its β-lactamase stability.

      • These characteristics allow cefoxitin to be viewed as a bridge between cephalosporins and later broad-spectrum β-lactams.⁴

    • Additional studies Describe cefoxitin exhibiting strong activity versus many cephalothin-resistant Enterobacterales and good coverage of Bacteroides fragilis.⁵

  • Mechanism of Action

    • Cefoxitin is a β-lactam that inhibits cell-wall synthesis by binding to penicillin-binding proteins (PBPs) (transpeptidases).

      • This activity the final cross-linking steps of peptidoglycan, leading to structurally fragile cell walls and ultimately bacterial lysis.^6,7

        • Points of emphasis include:

          • Bactericidal PBP-binding mechanism

          • Relative stability to many penicillinases and cephalosporinases.

          • Potent activity against anaerobes in the spectrum of Gram-negative rods.

  • Spectrum of activity

    • Major considerations

      • Gram-positive aerobes (MSSA, streptococci)^6,7 

        • Active against methicillin-susceptible Staphylococcus aureus and various streptococci (S. pyogenes, S. pneumoniae, S. agalactiae)

        • MRSA and enterococci are intrinsically resistant.

      • Gram-negative anaerobes

        • Cefoxitin exhibits good activity activity against many E. coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Haemophilus influenzae, and Neisseria gonorrhoeae.

        • Poor activity with cefoxitin has been noted for: Pseudomonas aeruginosa and many Enterobacter, Serratia, Citrobacter (especially AmpC-producers).

        • E. coli

          "Low-temperature electron micrograph of the cluster of E. coli bacteria magnify 10,000 times. Each individual bacterium is oblong shape." March 2005. Attribution Public domain. https://en.wikipedia.org/wiki/File:E_coli_at_10000x,_original.jpg

           

        • Klebsiella pneumoniae

          Klebsiella pneumoniae "Klebsiella is a genus of Gram-negative, oxidase-negative, rod -shaped bacteria where they prominent polysaccharide-based capsule." Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. p. 370. Example of Klebsiella species include Klebsiella aerogenes, Klebsiella pneumoniae, and Klebsiella variicola Attribution Janice Carr/ CDC, Public domain, via Wikimedia Comments. https://commons.wikimedia.org/wiki/File:Klebsiella-pneumoniae.jpg

        •  

          Haemophilus influenzae

          "Sputum Gram stain at 1000x magnification. The sputum is from the person with Haemophilus influenzae pneumonia, and the Gram-negative cocci bacilli are visible or the background of neutrophils." Attribution Microman12345, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Haemophilus_influenzae_sputum_1000x_edited.jpg

           

        • Chest radiograph and influenza and H. Influenza, posterioanterior, annotated JPEG

          "Chest x-ray of the case of Haemophilus influenzae, presumably as the secondary infection from influenza. It shows patchy consolidations, mainly in the right upper lobe (arrow)." Attribution Mikael Häggström, M.D. Author info - Reusing images- Conflicts of interest:  NoneMikael Häggström, M.D.Consent note: Written informed consent was obtained from the individual, including online publication., CC0, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Chest_radiograph_in_influensa_and_H_influenzae,_posteroanterior,_annotated.jpg

       

      • Anaerobes

        • Cefoxitin exhibits excellent activity vs Bacteroides spp., including B. fragilis, Clostridium spp., Peptostreptococcus, and related anaerobes.

          • Accordingly, this antibiotic is  especially attractive for intra-abdominal and pelvic infections.^6,8