General Principles of Antimicrobial Therapy

General Principles of Antimicrobial Therapy

1. Definitions & conceptual framework

• Chemotherapy = treatment of systemic infection with specific drugs that selectively suppress or kill the infecting microorganism without significantly affecting the host; the property exploited is selective microbial toxicity (KDT 8e Ch.50, pp.739–40).
  • The basis of selectivity is action on a microbial structure/process absent in the host (e.g. bacterial cell wall, folate synthesis) or high affinity for a microbial biomolecule (e.g. trimethoprim for bacterial dihydrofolate reductase) (KDT 8e Ch.50, p.739).
  • Because malignant cells resemble pathogenic microbes (rapidly dividing, foreign-like), anticancer drug therapy is also called "chemotherapy" by analogy (KDT 8e Ch.50, p.740).
• Antibiotic (strict definition) = a substance produced by a microorganism that selectively suppresses growth of or kills other microorganisms at very low concentrations — excluding antibody-type host products and microbe-derived substances active only at high concentration (ethanol, lactic acid, H₂O₂) (KDT 8e Ch.50, p.739).
• Antimicrobial agent (AMA) = the preferred umbrella term covering both synthetic and naturally derived drugs that attenuate microorganisms; G&G uses "antibiotic" colloquially to encompass antibacterial, antiviral, antifungal and antiparasitic agents (KDT 8e Ch.50, p.739; G&G 14e Ch.56, p.1127).
• Pharmacophore (Ehrlich) = the active chemical moiety of the drug that binds the microbial receptor; antimicrobials should be viewed as ligands whose receptors are microbial proteins that are essential components of microbial biochemical reactions (G&G 14e Ch.56, p.1127).
• Microorganisms of medical importance fall into four categories — bacteria, viruses, fungi, parasites — and the broad antibiotic classification follows this closely, though many agents (especially those targeting evolutionarily conserved pathways) cross categories (G&G 14e Ch.56, p.1127).
• Biochemical processes commonly inhibited by antimicrobials: cell-wall synthesis, cell-membrane synthesis/function, ribosomal translation, nucleic-acid metabolism, topoisomerase-mediated DNA conformational change, viral proteases/integrases/fusion proteins, folate synthesis, and parasitic detoxification; newer modalities include antisense antibiotics (sequence-specific gene-expression inhibition) and interferon-based antivirals (G&G 14e Ch.56, p.1127).