Chapter 9: Antimicrobial Drugs, Resistance & Chemotherapy

Key principles guiding drug efficacy are selective toxicity and the therapeutic index, alongside classifications like narrow- or broad-spectrum agents, and cidal (killing) or static (inhibiting) activity. Drug effectiveness is quantitatively measured using the minimal inhibitory concentration (MIC) and minimal lethal concentration (MLC), often determined through standardized techniques like dilution susceptibility tests, the disk diffusion (Kirby-Bauer) method, or the Etest. Antibacterial drugs are categorized by their cellular targets, including highly selective cell wall synthesis inhibitors (such as β-lactams like penicillins and cephalosporins, and vancomycin), protein synthesis inhibitors (e.g., aminoglycosides, tetracyclines, and macrolides), metabolic antagonists (like sulfonamides and trimethoprim, which block folic acid synthesis), and nucleic acid inhibitors (e.g., fluoroquinolones and rifamycins). The treatment of eukaryotic pathogens, fungi, and protozoa is complicated by their cellular similarity to human cells, leading to lower therapeutic indices; antifungals often target the sterol ergosterol in the fungal membrane, while antiprotozoan drugs target nucleic acid synthesis or metabolism, as seen in malaria and toxoplasmosis treatments. Antiviral agents specifically interfere with critical steps of the viral replication cycle, requiring drug combinations, particularly for HIV (NRTIs, PIs, fusion inhibitors) and Hepatitis C (direct-acting antivirals). Finally, the chapter addresses the critical global health threat of antimicrobial resistance, detailing mechanisms such as target modification (MRSA), drug inactivation ( β-lactamase enzymes), minimizing drug concentration (efflux pumps), and using alternate metabolic pathways, emphasizing that judicious use, antibiotic stewardship, and combination drug therapies are vital strategies needed to overcome this ongoing challenge.