Chapter 37: Principles of Antimicrobial Chemotherapy

Principles of Antimicrobial Chemotherapy traces the evolution of these agents from early antibiotic discoveries, such as penicillin, to the development of synthetic compounds like sulfonamides. Modern antimicrobial agents are classified based on their specific targets, including the inhibition of cell wall synthesis, protein synthesis, nucleic acid metabolism, or the disruption of cell membrane integrity. A critical distinction is made between bactericidal drugs, which actively destroy microbes, and bacteriostatic agents, which merely arrest microbial growth, necessitating a functional host immune system for clearance. Clinicians must consider the antimicrobial spectrum, ranging from narrow to broad, and evaluate key pharmacodynamic parameters such as the minimal inhibitory concentration (MIC), concentration-dependent killing rates, and the postantibiotic effect (PAE). The text details laboratory methods for sensitivity testing, including the Kirby-Bauer disk diffusion and E-test methods, to guide therapeutic choices. Furthermore, it addresses the significant challenge of microbial resistance, which arises through spontaneous mutation or the transfer of resistance factors via bacterial conjugation and plasmids. Mechanisms of resistance include enzymatic inactivation (such as by beta-lactamase), altered drug accumulation through efflux pumps or modified porins, and reduced target affinity. Successful therapy requires balancing host factors—such as age, immune status, pregnancy, and organ function—with drug characteristics like oral bioavailability, tissue penetration into sites like the central nervous system or bone, and adverse effect profiles. Finally, the chapter discusses the strategic use of combination drug therapy to achieve synergistic effects or prevent resistance, alongside the role of prophylactic treatment in surgical settings and disease prevention.