β‐Lactam Antibiotics

Abstract

This chapter reviews the history of β‐lactams from the discovery of penicillin in 1928 to the more recently studied and the current trends in the field. The most relevant aspects related to the mechanism of action of β‐lactams are covered, and the various mechanisms of resistance to currently available β‐lactams that bacteria have adopted since the introduction of penicillin are described. A classification of β‐lactamases and their relevance in clinics is also provided. Applications of β‐lactams both in the hospital and in the community are reported, with particular attention to their pharmacokinetic properties, related side effects, and their therapeutic indications. The history and discovery of β‐lactams are described and all major classes are covered: penicillins, cephalosporins, oxacephems, carbacephems, penems, monobactams and nocardicins, carbapenems and trinems, classical (e.g., clavulanic acid, sulbactam, tazobactam), and the more recently disclosed β‐lactamase inhibitors. Several aspects related to the most recent developments in β‐lactams are also covered: new molecules active against difficult Gram‐positive strains or endowed with an antibacterial broad spectrum of action; potent orally active β‐lactams; injectable β‐lactams; and β‐lactamase inhibitors. The chapter concludes with a continuing analysis of the industry‐driven trends and the most recent new application of β‐lactams as inhibitors of protein export in bacteria. Finally, a few very interesting Web addresses and a comprehensive reference list are also provided.

Isolation and Characterisation of Degradation Impurities in the Cefazolin Sodium Drug Substance

“…CZS is a broad-spectrum antibiotic, active in vitro against most Gram-positive and Gram-negative bacteria. Chemically, CZS is sodium (6 R ,7 R )-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1 H -tetrazol-1-yl-acetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate [ 1 – 4 ]. CZS is used in the form of intramuscular and intravenous injections for the treatment of infections of the respiratory system, urogenital system, infections of skin and soft tissues, biliary tract, bones, joints, and in endocarditis and septicaemia.…”