Chapter 38: Antibiotics That Inhibit Bacterial Cell Wall Synthesis

Focusing primarily on beta-lactam antibiotics, the text details how these agents—including various forms of penicillins, cephalosporins, monobactams, and carbapenems—bind to specific enzymes known as penicillin-binding proteins (PBPs) to halt the crucial cross-linking of the peptidoglycan layer. This disruption typically results in bacterial death, making these medications bactericidal. The discussion categorizes penicillins based on their clinical reach, from narrow-spectrum options like Penicillin G used for streptococcal infections and syphilis to extended-spectrum choices like piperacillin that combat gram-negative bacilli. It further examines several generations of cephalosporins, noting how their activity progressively shifts toward more resilient gram-negative organisms while maintaining coverage for gram-positive cocci. Advanced-generation agents such as ceftaroline are highlighted for their unique ability to treat methicillin-resistant Staphylococcus aureus (MRSA). To combat bacterial resistance driven by beta-lactamase enzymes, the chapter explains the role of inhibitors like clavulanate and avibactam, which serve as surrogate substrates to protect the primary antibiotic from destruction. Beyond the beta-lactams, the text covers glycopeptides like vancomycin, which interferes with cell wall precursors, and specialized drugs like bacitracin and fosfomycin. Pharmacokinetic considerations, such as the use of probenecid to prolong drug half-life and the significance of renal versus biliary excretion, are thoroughly analyzed alongside critical safety profiles, including hypersensitivity reactions, potential neurotoxicity leading to seizures, and specific side effects like red neck syndrome associated with rapid infusion.