Chapter 10 : Inhibitors of Peptidoglycan Biosynthesis

Abstract:

The carbapenems are a subgroup of β-lactam antibiotics with a common carbapenem nucleus. Carbapenems are broad-spectrum antibiotics with activity against gram-positive and gram-negative bacteria. Like other β-lactam antibiotics, imipenem and thienamycin interfere with the biosynthesis of the peptidoglycan polymer. The discovery of the excellent activity of the imipenem-cilastatin combination against a wide variety of aerobic and anaerobic microorganisms led to extensive work on the isolation of other naturally occurring carbapenems by pharmaceutical laboratories worldwide as well as on the production of synthetic compounds. In vitro, meropenem, like imipenem, is active against most clinically important gram-positive and gram-negative aerobes and anaerobes. Both imipenem and meropenem are inactive against methicillin-resistant staphylococci, Enterococcus faecium, or Stenotrophomonas maltophilia. Ertapenem is a new β-lactam antibiotic belonging to the carbapenem subgroup. It possesses a 1-β-methyl group on the carbapenem nucleus. Unlike the penicillins, cephalosporins, and carbapenems, which are bicyclic compounds, the monobactams are monocyclic β-lactam antibiotics. The first monobactams to be discovered were naturally occurring compounds isolated from bacteria, but they exhibited poor antibacterial activity. These naturally occurring monobactams are characterized by the 2-oxoazetidine-1-sulfonic acid moiety with an acyl side chain at the 3 position with the β-orientation and, for most monobactams, a 3-α-methoxy group. The potent antibacterial activity of aztreonam is directed specifically against aerobic gram-negative bacteria. This activity varies from high against organisms such as Neisseria and Haemophilus spp. to intermediate against Pseudomonas aeruginosa to poor against Acinetobacter spp.