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Chapter 9 : Inhibitors of Peptidoglycan Biosynthesis
This chapter provides an overview on inhibitors of peptidoglycan biosynthesis cephalosporins. The clinical use of cephalosporin C was limited by its generally weak antibacterial activity. With the penicillins as a precedent, the 7-acylamino group was the first target for variation in the search for improved activity. The first-generation cephalosporins are used to treat Staphylococcus aureus and nonenterococcal streptococcal infections when it is necessary to avoid the use of penicillin. The second-generation cephalosporins should be considered in three groups: the true cephalosporins, the cephamycins, and the carbacephems. The first is a syn-oxime, found in cefuroxime as well as in other third- and fourth-generation cephalosporins. The effectiveness against gram-negative bacteria that is so notable in carbenicillin and ticarcillin (which is attributed to the α-COOH group on the acyl side chain) is also present in moxalactam. As in amoxicillin, the p-OH group on the benzene ring is incorporated in moxalactam to increase the level of drug in blood and to increase its half-life. The 1-methyl-tetrazolyl group at position 3, which has been useful in several third-generation cephalosporins, was also incorporated into the structure of this molecule. The first-generation cephalosporins have a spectrum that includes E. coli, K. pneumoniae, P. mirabilis, and most gram-positive cocci, although not enterococci or methicillin-resistant enterococci. The second-generation cephalosporins have broader in vitro activity against gram-negative bacteria. The third-generation cephalosporins are more active than first- and second-generation drugs against gram-negative organisms.