Antimicrobial Dosing Principles

Determinants of Rational Dosing

• Rational dosing hinges on pharmacodynamics and pharmacokinetics, influencing dosing frequency.
• Three key properties affect dosing frequency:
  • Concentration-dependent killing
  • Time-dependent (concentration-independent) killing
  • Postantibiotic effect (PAE)

Combinations of Antimicrobial Drugs

• Single-agent therapy is preferred to minimize superinfections and toxicity while reducing resistance emergence.
• In specific cases, drug combinations are beneficial.
• Notable effective combinations include β-lactams and aminoglycosides.

Selecting Antimicrobial Agents

• Drug-Bacteria Factors:
  • Consider antibacterial spectrum, mechanism of action, selective toxicity, and organism susceptibility.
  • Assess time-dependent vs. concentration-dependent effects and the need for bactericidal vs. bacteriostatic agents.
• Host-Bacteria Factors:
  • Factor in host defense and the necessity of antimicrobial agents.
  • Differentiate between empiric, definitive, and prophylactic therapy as well as combination therapy.
• Drug-Host Factors:
  • Consider pharmacokinetics, age, allergy history, and metabolic abnormalities.

Classes of Antibacterial Agents

• Antimicrobial agents can be classified by:
  • Their effect on bacteria (bactericidal vs. bacteriostatic).
  • Their antibacterial spectrum (broad, narrow, or extended spectrum).
  • Their mode of action.

Effect on Bacteria

• Bactericidal Agents: Kill microorganisms, requiring no host defense mechanisms (e.g., penicillins).
• Bacteriostatic Agents: Stop microbial growth, dependent on host defenses (e.g., tetracyclines).

Antibacterial Spectrum

• Broad Spectrum: Effective against a wide range of organisms (e.g., tetracyclines).
• Narrow Spectrum: Target specific organisms (e.g., penicillin G for gram-positive bacteria).
• Extended-Spectrum: Modified to act on both gram-positive and significant gram-negative bacteria (e.g., ampicillin).

Mode of Action

• Inhibitors of Cell Wall Synthesis: Target peptidoglycan structure, leading to cell lysis (e.g., β-lactam antibiotics).
• Inhibitors of Cell Membrane Function: Disrupt membrane functionality (e.g., polymyxins).
• Inhibitors of Protein Synthesis: Target bacterial ribosomes, can be bactericidal or bacteriostatic (e.g., aminoglycosides).
• Inhibitors of Nucleic Acid Synthesis: Block DNA or RNA synthesis (e.g., quinolones).
• Inhibitors of Metabolic Pathways: Interfere with essential metabolic processes (e.g., sulfonamides).

Selective Toxicity

• Antimicrobials should selectively target pathogens without harming host cells, leveraging differences in structure/metabolism.

Drug Resistance Overview

• Bacteria are considered resistant if antibiotics cannot inhibit their growth.
• Resistance can be inherited or acquired.
• Development of resistance is facilitated by genetic mutations and horizontal gene transfer.

Causes of Antimicrobial Resistance

• Reduced drug entry and enhanced export (efflux pumps).
• Microbial enzymes degrading antibiotics.
• Alterations in drug target structures.
• Metabolically inactive bacteria resist treatment.

Factors Contributing to Antimicrobial Resistance (AMR)

• Overuse and misuse by healthcare providers.
• Patient noncompliance and self-medication.
• Antibiotic use in agriculture and aquaculture.
• Inadequate infection control measures in healthcare settings.
• Lack of new antibiotics entering the market.

Considerations in Antimicrobial Therapy

• Identification of the infecting organism is critical for effective treatment.
• Site of infection influences drug choice (e.g., blood-brain barrier).
• Patient factors such as immune status and organ function are vital for therapy selection.

This quiz explores the determinants of rational dosing of antimicrobial agents, focusing on pharmacodynamics and pharmacokinetics. It highlights crucial properties that influence dosing frequency, including concentration-dependent killing and time-dependent killing. Test your knowledge on these key concepts.