cefazolin

cefazolin
IUPAC name	(6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Width	200
Tradename	Ancef, Kefzol, others
Drugs.com	monograph, cefazolin
MedlinePlus	a682731
Routes of administration	Intravenous, intramuscular
CAS number	25953-19-9
PubChem	33255
DrugBank	DB01327
ChemSpiderID	30704
UNII	IHS69L0Y4T
ChEBI	474053
ChEMBL	1431
Chemical formula	C14H14N8O4S3
Molecular weight	454.51 g·mol−1
Melting point	198–200 °C (decomposes)

cefazolin. It is a first-generation cephalosporin antibiotic used to treat a variety of bacterial infections. Developed in the late 1960s, it is particularly effective against Gram-positive bacteria such as Staphylococcus aureus and is commonly employed for surgical site infection prophylaxis. Its administration is typically via intravenous or intramuscular injection routes due to poor oral absorption.

Medical uses

Cefazolin is indicated for the treatment of serious infections caused by susceptible strains of microorganisms. It is a cornerstone agent for surgical prophylaxis, especially in clean-contaminated surgery involving the cardiothoracic, vascular, orthopedic, and obstetrical fields, as recommended by guidelines from the American Society of Health-System Pharmacists. It is effective against many isolates of Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus. The World Health Organization includes it on its Model List of Essential Medicines. It is also used to treat bacterial endocarditis, biliary tract infections, and infections of the respiratory tract, skin, and bone.

Adverse effects

Adverse reactions are generally similar to those of other beta-lactam antibiotics. Common effects include pain at injection site, phlebitis, and gastrointestinal disturbances such as nausea and diarrhea. Hypersensitivity reactions, ranging from skin rash to severe anaphylaxis, can occur, particularly in patients with a history of penicillin allergy. As with many cephalosporins, there is a risk of ''Clostridioides difficile''-associated diarrhea. Rare but serious adverse effects include neutropenia, thrombocytopenia, and transient elevations in liver function test results, such as those from the aspartate transaminase and alanine transaminase enzymes.

Pharmacology

Cefazolin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to specific penicillin-binding proteins located inside the bacterial cell wall, which in turn inhibits the final step of peptidoglycan synthesis in the bacterial cell wall. It is not well absorbed from the gastrointestinal tract, necessitating parenteral administration. It is widely distributed in most body tissues and fluids, achieving high concentrations in bile and synovial fluid, but penetration into the cerebrospinal fluid is poor. Excretion is primarily via the kidneys through glomerular filtration and tubular secretion, with a half-life of approximately 1.8 hours in adults with normal renal function.

Chemistry

Cefazolin is a semisynthetic cephalosporin antibiotic. Its chemical structure features a beta-lactam ring fused to a dihydrothiazine ring, constituting the fundamental cephem nucleus. A distinguishing feature is the substitution at the 3-position of the cephem ring with a methylthiadiazolethiol group, which contributes to its stability against certain beta-lactamase enzymes. The side chain at the 7-position is a tetrazolylacetyl group. It is supplied as a sodium salt, which is highly soluble in water and methanol but insoluble in most organic solvents like chloroform.

History

Cefazolin was developed in 1969 by the Japanese pharmaceutical company Fujisawa Pharmaceutical Co. (now part of Astellas Pharma). Its development followed the discovery of the first cephalosporin C by Giuseppe Brotzu and the subsequent work at the Sir William Dunn School of Pathology in Oxford. Cefazolin was part of a wave of first-generation cephalosporins synthesized to improve upon the spectrum and pharmacokinetics of earlier agents like cephalothin. It received approval from the U.S. Food and Drug Administration in 1973 and was marketed under trade names including Ancef and Kefzol.

Society and culture

Cefazolin is available as a generic medication and is considered cost-effective for many institutional uses. It is on the World Health Organization's List of Essential Medicines. In many regions, its use for surgical prophylaxis is governed by institutional antimicrobial stewardship programs to prevent overuse and resistance. High-profile incidents, such as a 2011 contamination event at the New England Compounding Center, have involved cefazolin, highlighting issues in pharmaceutical compounding safety. Its role in preventing post-surgical infections is frequently cited in guidelines from the Centers for Disease Control and Prevention and the Surgical Infection Society.

Category:Cephalosporin antibiotics Category:World Health Organization essential medicines Category:Antibiotics