Peripheral brain: cephalosporins.

Abstract

1. Barbara A. Jantausch, MD* 1. *Department of Infectious Diseases, Children’s National Medical Center; Associate Professor of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC After completing this article, readers should be able to: 1. Describe the activity of first-generation cephalosporins and the primary infections they are used to treat. 2. Describe the activity of second-generation cephalosporins and the primary infections they are used to treat. 3. List the types of infections for which cefoxitin is used. 4. Explain the use of third-generation cephalosporins. 5. List the pathogens against which ceftazidime is effective and how the agent is used clinically. 6. Describe the pathogens against which vancomycin is effective and how the agent is used clinically. In the mid-1940s, products of the mold Cephalosporium acremonium were noted to inhibit the growth of bacteria in seawater contaminated by sewage. A decade later, cephalosporin C, the parent compound of the cephalosporins, was isolated from C acremonium . The first cephalosporin, cephalothin, was marketed in 1964. A large number of cephalosporins were developed subsequently, and today there are four generations of cephalosporins and more than 20 cephalosporin antibiotics. This review examines the properties of the first four generations of cephalosporin antibiotics, focusing on those used commonly in children. The structure of the cephalosporin antibiotic is a beta-lactam ring fused to a six-membered dihydrothiazine ring. Substitutions at positions 1, 3, and 7 of this cephem nucleus influence the chemical properties and antimicrobial spectrum of the resultant antibiotic. Cephalosporins interrupt the synthesis of the peptidoglycan component of bacterial cell walls by binding to and inhibiting penicillin-binding proteins (PBPs). PBPs are enzymes located in the cytoplasmic membrane of gram-positive and gram-negative bacteria that are required for cell wall synthesis. PBPs are unique in different bacterial species. The cephalosporins have varying affinities for PBPs, which helps to explain their differences in antimicrobial spectrum. Bacteria resist the antimicrobial effects of cephalosporins by: 1) altering their PBPs, 2) producing beta-lactamase enzymes that inactivate cephalosporins, and 3) changing their outer cell …