Antibacterials and Tuberculosis Overview

Antibacterials and Tuberculosis

• Learning outcomes include describing bacterial cell structure, key terms related to antibacterial drugs, antibacterial drug targets, and the pathophysiology, risk factors, signs/symptoms, and pharmacotherapy of tuberculosis.

Chemotherapy and Antibiotics

• Chemotherapy, developed in the early 20th century, utilizes synthetic chemicals to target diseases.
• Alexander Fleming's 1928 discovery of penicillin revolutionized medicine.
• Antibiotics are substances created by microorganisms or synthesized as chemicals.
• Antibiotics are selectively toxic, meaning they target microbes without harming human hosts.

Bacterial Cell

• Bacterial cell walls are composed of peptidoglycan (except in Mycoplasma).
• The cell membrane is a phospholipid bilayer with proteins.
• The cytoplasm does not contain mitochondria or a nucleus.
• Bacteria have a single circular chromosome.
• The presence of an outer membrane is used to identify bacteria as Gram-positive or Gram-negative.

Selective Toxicity

• Drug targets include the cell wall, cytoplasmic membrane, protein synthesis and nucleic acid metabolism.

Antibacterials - Terms

• Bacteriostatic agents inhibit bacterial multiplication (e.g., sulfonamides, tetracyclines, chloramphenicol.)
• Bactericidal agents kill bacteria (e.g., penicillins, aminoglycosides, rifampicin).
• Minimum inhibitory concentration (MIC) measures the lowest concentration of an antimicrobial needed to stop bacterial growth.
• Minimum bactericidal concentration (MBC) is the lowest concentration that kills the bacteria.

Drug Targets

• Antibacterial drugs target various bacterial components such as cell walls (β-lactams, cephalosporins, glycopeptides), plasma membranes (polymyxins), ribosomes (aminoglycosides, tetracyclines), DNA synthesis (fluoroquinolones), RNA synthesis (rifamycins), and metabolic pathways (sulfonamides, trimethoprim).

Drug Targets: Class I, II, and III

• Class I targets energy production from glucose/carbohydrates.
• Class II targets basic carbon compounds converted from Class I metabolites into small molecules like amino acids, nucleotides, and others.
• Class III targets small molecules from Class II into macromolecules such as proteins, RNA, DNA, polysaccharides
• Class I targets are not ideal targets for antibiotics; Class II is a better target, and Class III is an excellent target.

Drug Targets: Class II (Folates)

• Bacteria synthesize folate, and humans do not.
• Sulfonamides inhibit folate synthesis; trimethoprim inhibits folate utilization.
• Co-trimoxazole (sulfonamide + trimethoprim) is effective against Pneumocystis jirovecii.