Chapter 8 : Inhibitors of Peptidoglycan Biosynthesis

Abstract:

This chapter provides an overview on inhibitors of peptidoglycan biosynthesis. Derivatives of penicillanic acid comprise two groups of therapeutic agents of considerable importance in medicine: the antibacterial penicillins and the β-lactamase inhibitors. Penicillin G (benzylpenicillin) and penicillin V (phenoxymethylpenicillin) are the only penicillins used in their natural forms as obtained from the fermentation of Penicillium chrysogenum. The other penicillins in clinical use are derived from 6-β-aminopenicillanic acid using standard synthetic procedures. The structural modification in the side chain of antistaphylococcal β-lactamase-resistant semisynthetic penicillins provides enough steric hindrance to make them very poor substrates for most β-lactamases. Nafcillin and the isoxazolyl penicillins also are used only for treatment of infection due to β-lactamase-producing staphylococci. The aminopenicillins include ampicillin, its ethoxycarbonyloxyethyl ester (bacampicillin), and amoxicillin. The antipseudomonal penicillins are semisynthetic derivatives of penicillanic acid and are categorized into two subgroups: the carboxypenicillins, which include carbenicillin indanyl ester (an ester for oral administration) and ticarcillin, and the ureidopenicillins, which include mezlocillin and piperacillin. Antipseudomonal penicillins retain most of the antibacterial activity of the aminopenicillins but have added activity against gram-negative bacilli. Indanyl carbenicillin (with a carboxyl side chain) is well absorbed from the gastrointestinal tract and is hydrolyzed by esterases to carbenicllin, the active drug. In the treatment of moderate to severe Pseudomonas infection, an aminoglycoside of the antipseudomonal group (gentamicin, tobramycin, or amikacin) is often administered along with an antipseudomonal penicillin (mezlocillin or piperacillin).