Antimicrobial Drugs Overview

Antimicrobial Drugs

• Antimicrobial agents kill or prevent the growth of microorganisms.
• These agents can be classified according to the type of microorganism they target: antibiotics (bacteria), antifungals (fungi), antivirals (viruses), and antiparasitics (parasites)
• Antimicrobial drugs work by disrupting metabolic processes or structural components of the targeted microorganism.
• Microbicidal agents kill microbes; microbiostatic agents inhibit their growth.

Learning Outcomes

• Understand and compare different mechanisms of antimicrobial action.
• Define characteristics of antimicrobial drugs.
• Explain antimicrobial resistance mechanisms.
• Name specific antimicrobial drugs and their mechanisms of action.

What is an Antimicrobial?

• Antimicrobials are medicines that fight infections caused by microorganisms in humans, animals, and plants.
• Different kinds of antimicrobials exist like Antibiotics (e.g. against bacteria), Antifungals, Antivirals or Antiparasitics.
• They can be microbiocidal (killing microbes) or microbiostatic (preventing growth).
• Antimicrobials are often targeted at specific types of microorganisms

Principles of Drug Action

• Drugs alter physiological activities.
• They must reach their intended target in an appropriate concentration.
• Pharmacokinetics is involved in this process. It is the study of how the body handles a drug.
• Aspects of pharmacokinetics include: drug administration, absorption, distribution, biotransformation, and clearance.

Drug Administration

• Drugs can be administered orally (digestive route) or parenterally (any other route)
• Absorption is the rate at which the drug leaves the site of administration and is taken into the body, and how efficiently it reaches the target site.
• Drugs have to be dissolved in body fluids to be absorbed.
• Drugs have to pass through biological barriers to reach their intended target areas in the body.

Drug Distribution

• Transferring drugs across biological membranes into body compartments.
• Drug distribution depends on chemical properties (e.g., solubility), blood flow, molecular size, and more.
• The blood-brain barrier can hinder drug distribution.
• The placenta acts as a pathway for drugs to cross.

Biotransformation

• The liver plays the primary role in drug metabolism.
• Other organs (lungs, kidneys, adrenal glands) are also involved.
• Drug metabolites must be water-soluble for excretion by the kidneys.

Clearance

• Mainly involves the kidneys (glomerular filtration, tubular reabsorption, tubular secretion).
• Some drugs are metabolized in the liver and excreted via bile.

Mechanisms of Antimicrobial Action

• Goal: disrupt the microorganism's metabolism or structure to prevent survival or reproduction.
• Microbicidal: Kills microbes; can potentially kill normal flora, leading to potential superinfection.
• Bacteriolytic: Kills/lyses the cells of the target microorganism.
• Microbiostatic: Inhibit growth, reversible.

Spectrum of Action

• Broad spectrum: effective against a wide range of microorganisms.
• Narrow spectrum: effective against a limited variety of organisms (avoiding damage to normal flora).
• Medium spectrum: effective against some gram-positive and gram-negative bacteria (not all).

Antimicrobial Agents

• Many different types of microorganisms exist (bacteria, eukaryotes, viruses, parasites).
• One drug does not effectively combat all microbes, as their structures and functions differ.
• Different drugs target different microbes.

Selective Toxicity

• Antimicrobial drugs should selectively affect harmful microbes while minimizing harm to host cells.
• Prokaryotic (bacteria) cell components are different from eukaryotic (animal) components, allowing for selective targets within the bacteria.

Mode of Action

• Many antimicrobials block critical metabolic pathways in the target organism, targeting specific processes such as cell wall, DNA/RNA synthesis, protein synthesis, plasma membranes, etc)

Inhibition of Cell Wall Biosynthesis

• Beta-lactam antibiotics (e.g., penicillin) interfere with cell wall formation in bacteria. (by binding to penicillin-binding proteins).
• Bacteria require peptidoglycans for the cell wall.
• Resistance to antibiotics can occur when bacteria have mutated and the antibiotic no longer works on them.

Inhibition of Protein Synthesis

• Drugs inhibiting protein synthesis in bacteria affect the ribosomes and block the process.
• Different classes of antibacterials target these steps to prevent protein synthesis in bacteria.

Disruption of Plasma Membrane

• Polymyxins disrupt bacterial membranes.
• These are not selective as they also damage eukaryotic cells.

Inhibition of Nucleic Acid Synthesis

• Quinolones block DNA supercoiling by binding to topoisomerases.
• Inhibiting DNA replication/synthesis in bacteria.

Inhibition of Metabolic Pathways

• Some drugs work as antimetabolites, stopping critical metabolic pathways (e.g., inhibiting folic acid synthesis).
• They are competitive inhibitors, targeting specific enzymes.

Resistance to Antimicrobial Drugs

• Overprescription, incomplete treatment courses, poor infection control, and misuse in agriculture are some factors promoting microbial resistance to drugs.
• Resistant microbes can survive, and their resistant genes can transfer to other microbes.
• Limited discovery of new antimicrobials.
• Mechanisms of resistance in microbes can include changes in membrane permeability, changes in the mechanism of action in target site, changes in metabolic pathways, and new/efficient enzymes developed in resistance.

Antimicrobial Susceptibility Tests (AST)

• Methods like Kirby-Bauer disk diffusion are used to determine the susceptibility of microbes to different antimicrobials, providing important information for treatment considerations.

Acquisition of Drug Resistance

• Improper use of prescribed antimicrobials promotes the development of resistant microbes.
• Microbes can develop various mechanisms to avoid the effects of the drug treatment.
• Misuse and overprescription of antimicrobials has led to drug-resistant bacteria.

Multiple Resistances

• Antibiotic resistance is a global problem—especially prevalent in healthcare facilities.
• Bacteria that are resistant to multiple antibiotics are called superbugs—they are a major threat to public health.

Preventing Drug Resistance

• Strategies for preventing drug resistance include careful prescriptions, proper duration of treatment, and addressing resistance issues in agriculture and healthcare environments.
• Education plays an important role in reducing antibiotic misuse and promoting appropriate antibiotic stewardship across populations.

Antiviral Agents

• Most viruses lack a cure and have limited effectiveness.
• Resistance to antivirals is also a concern.
• Targeting points in the viral life cycle (penetration, transcription/translation, maturation) often involves preventing the virus from reproducing and spreading.

Antifungal Agents

• Antifungal agents are used to treat fungal infections.
• They often have more side effects on eukaryotic cells than prokaryotic cells, and this can lead to complications.
• Some antifungals target fungal cell membrane functions or nucleic acid synthesis; some examples include macrolide polyene, synthetic azoles, and flucytosine.

Antiprotozoal Agents

• These agents combat protozoan infections.
• Examples include chloroquine, primaquine, metronidazole, pyrimethamine, and quinine.
• These agents are used to treat infections like malaria, giardiasis, and trichomoniasis.

Antihelminthic Agents

• Agents targeting helminths (eukaryotic parasite worms).
• They are designed to inhibit helminthic metabolism or movement.
• Agents including niclosamide, mebendazole, piperazine, and ivermectin are used to treat helminthic infections.