General Principles of Antimicrobial Therapy

Introduction & definitions

• Chemotherapy = treatment of systemic infection with drugs that selectively suppress/kill the pathogen without significantly harming the host; the property exploited is selective microbial toxicity — action on a target absent in the host (cell wall, folate synthesis) or higher affinity for a microbial molecule (trimethoprim for bacterial DHFR).
• Antibiotic (strict sense) = a substance produced by a microorganism that suppresses/kills other microbes at very low concentration; antimicrobial agent (AMA) is the preferred umbrella term covering synthetic + naturally derived agents (antibacterial, antiviral, antifungal, antiparasitic).
• Antimicrobials are best viewed as ligands whose receptors are essential microbial proteins (Ehrlich's pharmacophore); processes inhibited include cell-wall/membrane synthesis, ribosomal translation, nucleic-acid metabolism, topoisomerases, folate synthesis, and viral proteases/integrases.
• Bacteriostatic vs bactericidal — cell-wall-active agents (β-lactams, vancomycin) and aminoglycosides/fluoroquinolones/rifampin/metronidazole are generally cidal; protein-synthesis inhibitors (tetracyclines, chloramphenicol, macrolides, clindamycin, linezolid) and sulfonamides are generally static. The distinction is conditional (static drugs may be cidal at high concentration/in urine).