cefoxitin

cefoxitin
IUPAC name	(6R,7S)-3-(carbamoyloxymethyl)-7-methoxy-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Width	200
Tradename	Mefoxin
CAS number	35607-66-0
DrugBank	DB01329
UNII Ref	correct, FDA
UNII	6OEV9DX57Y
ATC prefix	J01
ATC suffix	DC01
PubChem	441199
ChemSpiderID	390013
ChEBI	3505
ChEMBL	503
C	16
H	17
Molecular weight	427.45 g/mol
Smiles	CO/N=C(/C1=C(COC(N)=O)CS[C@H]2[C@@H](N1C(=O)[C@H]2NC(=O)Cc3sccc3)C(=O)O)C
Protein bound	65 to 79%
Metabolism	Hepatic
Elimination half-life	41 to 59 minutes
Excretion	Renal

cefoxitin is a semisynthetic, broad-spectrum antibiotic belonging to the cephamycin class, which is structurally related to cephalosporins. It is marketed under the brand name Mefoxin and is primarily used for the treatment of infections caused by susceptible anaerobic bacteria and certain Gram-negative bacteria. Its development by Merck & Co. represented a significant advancement in targeting Bacteroides fragilis and other pathogens involved in intra-abdominal infections and pelvic inflammatory disease.

Medical uses

Cefoxitin is indicated for the treatment of serious infections caused by susceptible strains of microorganisms, including lower respiratory tract infections such as pneumonia and lung abscess. It is a drug of choice for gynecological infections like pelvic inflammatory disease, often caused by Neisseria gonorrhoeae and anaerobic bacteria. The antibiotic is also frequently employed in the management of intra-abdominal infections, including those following gastrointestinal surgery or resulting from perforated appendix, and for skin and skin structure infections. Its spectrum includes activity against many Bacteroides species, including Bacteroides fragilis, which are common in mixed infections. Prophylactic use is common in colorectal surgery to reduce the risk of surgical site infection.

Adverse effects

Common adverse effects associated with cefoxitin include local reactions at the injection site, such as phlebitis and thrombophlebitis. Gastrointestinal disturbances like diarrhea, nausea, and vomiting may occur, with pseudomembranous colitis reported due to overgrowth of Clostridioides difficile. Allergic reactions can range from skin rash and urticaria to more severe manifestations like Stevens-Johnson syndrome and anaphylaxis. Hematologic effects such as eosinophilia, neutropenia, and thrombocytopenia have been observed, along with transient increases in liver function tests and serum creatinine. Patients with a history of penicillin allergy may have cross-reactivity.

Pharmacology

Cefoxitin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to essential penicillin-binding proteins. It is resistant to degradation by many beta-lactamase enzymes produced by Gram-negative bacteria and anaerobic bacteria, which extends its spectrum. The drug is not well absorbed orally and must be administered via intravenous or intramuscular injection. It is widely distributed into body tissues and fluids, including peritoneal fluid, pleural fluid, and synovial fluid, but achieves poor penetration into the cerebrospinal fluid. Metabolism is minimal, with the majority excreted unchanged by the kidney via glomerular filtration and tubular secretion.

Chemistry

Cefoxitin is a semisynthetic cephamycin antibiotic, derived from cephamycin C produced by the bacterium Streptomyces lactamdurans. Its chemical structure features a beta-lactam ring fused to a dihydrothiazine ring, characteristic of cephalosporins, with a 7-alpha-methoxy group that confers stability against many beta-lactamase enzymes. A carbamoyloxymethyl group at the 3-position and a 2-thiopheneacetamido side chain at the 7-position complete its molecular architecture. It is supplied as a white to off-white crystalline powder of the sodium salt, which is highly soluble in water and physiological saline.

History

Cefoxitin was developed in the 1970s by researchers at Merck & Co. as part of a program to discover beta-lactam antibiotics with enhanced stability against beta-lactamase enzymes. Its discovery was closely tied to the isolation of cephamycin C from Streptomyces lactamdurans by the Merck Sharp & Dohme team. The Food and Drug Administration approved cefoxitin for clinical use in the United States in 1978 under the brand name Mefoxin. Its introduction provided a critical therapeutic option for mixed aerobic-anaerobic infections, particularly in abdominal surgery and obstetrics and gynecology, during an era of increasing antibiotic resistance.

Society and culture

Cefoxitin is on the World Health Organization's List of Essential Medicines, underscoring its importance in global health systems. It is available as a generic medication in many countries, increasing its accessibility. The drug has been a subject of various clinical guidelines, including those from the Infectious Diseases Society of America for treating pelvic inflammatory disease and the Surgical Infection Society for antimicrobial prophylaxis in surgery. Its role has been studied in major medical centers like the Mayo Clinic and Johns Hopkins Hospital. While newer agents like carbapenems and piperacillin/tazobactam have emerged, cefoxitin retains a niche in specific protocols within hospitals such as the Cleveland Clinic.

Category:World Health Organization essential medicines Category:Cephalosporin antibiotics Category:Merck & Co.