Concepts of Antimicrobials

Concepts of Antimicrobial Therapy

Chemotherapy

  • Chemotherapy refers to the use of drugs specifically designed to treat diseases, notably infections caused by microbes.

  • Paul Ehrlich, a pioneer in the field, proposed the concept of chemotherapy with his idea of "magic bullets," which are drugs that target pathogens without harming the host.

    • He is known for discovering an arsenic compound (called Salvarsan, Arsephenamine, or Compound 606; as his 606th arsenic compound tested) effective against the protozoan causing sleeping sickness (trypanosomiasis) and also found effective against bacterial syphilis (caused by Treponema pallidum).

Selective Toxicity

  • Selective toxicity is a crucial principle of antimicrobial therapy.

    • It indicates the ability of a drug to kill harmful microbes while sparing human cells or without harming the host, thereby minimizing side effects.

Antimicrobial Drugs

  • Antimicrobial drugs are substances that kill or inhibit the growth of microbes within a host.

    • This broad category includes not just antibiotics (which target bacteria) but also antifungals (targeting fungi), antivirals (targeting viruses), and antiparasitics (targeting parasites).

Antibiotic

  • An antibiotic is defined as a naturally occurring substance produced by one microbe that kills or inhibits the growth of another microbe.

    • Antibiotics are commonly categorized into several classes based on their mechanisms of action, including penicillins, cephalosporins, tetracyclines, and macrolides.

Characteristics of Bacteria

  • Bacteria belong to the group of organisms known as prokaryotes.

    • They are characterized by the absence of a nucleus and membrane-bound organelles, which differentiates them from eukaryotic cells.

    • Bacteria are unicellular organisms that can be found in various environments, including soil, water, and living organisms.

    • They reproduce asexually through a process called binary fission, where a single bacterial cell divides into two identical daughter cells.

Structure of Bacterial Cell

Components (CPPNCRFPC)

  1. Capsule

    • This is the outermost layer providing the first line of defense for bacteria, helping them evade phagocytosis (the engulfing of bacteria by immune cells) and providing resistance to pressure changes.

      • The capsule is absent in mammalian cells.

  2. Plasma Membrane

    • Composed of a phospholipid bilayer, the plasma membrane acts as a selective or semi-permeable barrier that regulates the entry and exit of substances.

    • It plays a role in energy production and nutrient transport.

  3. Plasmids

    • Plasmids are small, circular pieces of DNA distinct from the chromosomal DNA.

    • They often carry genes that confer antibiotic resistance (R-Plasmids) or virulence factors that enhance pathogenicity.

  4. Nucleoid (DNA)

    • The nucleoid contains the bacterial chromosome (DNA), which consists of circular DNA.

    • This is essential for the bacterial reproductive process.

  5. Cytoplasm

    • The cytoplasm is the gel-like substance and liquid component where cellular processes occur.

    • It contains enzymes and substrates necessary for metabolism.

  6. Ribosome

    • Ribosomes are crucial for protein synthesis and are composed of RNA and proteins.

    • Prokaryotic ribosomes are smaller than eukaryotic ribosomes (70S vs. 80S).

  7. Flagellum

    • A long, whip-like structure that enables bacterial motility and movement.

    • Bacteria can be single-flagellated or have multiple flagella.

  8. Pilus or Pili

    • Pili are hair-like structures that assist in attachment to surfaces and other bacterial cells.

    • They can facilitate genetic exchange between bacteria during conjugation.

  9. Cell Wall

    • The cell wall provides structural integrity, composed of peptidoglycan, and determines whether bacteria are gram-positive or gram-negative.

      • Peptidoglycan is made up of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) units, and the cross-linking occurs via transpeptidation, where the Penicillin Binding Proteins (PBPs) facilitate the removal of the terminal alanine (called D-alanyl-D-alanine) in the NAM structure.

    • Gram-Positive Bacteria:

      • Characterized by a thick layer of peptidoglycan, it retains the crystal violet stain and appears violet/purple under a microscope.

    • Gram-Negative Bacteria:

      • Characterized by a thin layer of peptidoglycan and an outer membrane containing lipopolysaccharides (such as Lipid A or Toxic A), which can act as toxins.

        • These bacteria do not retain the crystal violet stain and appear pink (using safranin as counterstain) after a Gram stain.

    • Note: Both gram-positive and gram-negative have the same phospholipid plasma membrane.

Microbial Flora

  • The human body hosts a wide range of bacteria known as microbial flora or microbiota.

    • These organisms are essential for various bodily functions, including digestion, metabolism, and competition with potential pathogens, thus providing a protective role.

Antimicrobial Resistance

Reasons (OMI)

  1. Overuse of Antibiotics: Excessive prescribing for both human and agricultural use.

  2. Misuse of Antibiotics: Incomplete courses, using antibiotics for viral infections, etc.

  3. Inevitability of Resistance Development: As bacteria replicate quickly, the emergence of resistant strains is an ongoing challenge.

Mechanisms of Resistance (PEIMASB)

  1. Prevent Entry: Alteration of porins or membrane structures that prevent antibiotic penetration.

  2. Efflux of Antibiotic: Active pumping of antibiotics out of the bacterial cell.

  3. Inactivation via Enzyme: The most common mechanism, where bacteria produce enzymes (like beta-lactamases) that deactivate antibiotics.

  4. Modification of Target: Changes in the target site of the antibiotic, rendering it ineffective.

  5. Avoid Utilization Target: Bacteria may alter metabolic pathways to avoid using the target molecule.

  6. Spontaneous Mutations: Errors during DNA replication can lead to resistance.

  7. Bacterial Conjugation: Transfer of resistance genes via R-plasmids between bacteria can spread resistance rapidly.

Prevention Strategies (AU)

  1. Adhere to Prescribed Antibiotic Regimens: Ensures complete treatment courses to minimize resistance development.

  2. Use Antibiotics Judiciously: Prescribe antibiotics only when necessary and appropriate treatments are available, avoiding misuse.