Chapter 20 : Antimicrobial Drugs

Antimicrobial Drugs In-Depth Notes

Overview of Antimicrobial Drugs

• Antimicrobial drugs help treat diseases when the body's natural defenses fail.

• They function by killing microorganisms or inhibiting their growth.

• Key principle: selective toxicity - drugs must target pathogens without harming the host.

• Examples include chemotherapy with antimicrobial drugs, antibiotics, and their resistance.

Definitions :

• Chemotherapy : Use of drugs to treat disease

• Antibiotics : Interfere with growth of microbes within a host

• Selective toxicity : A drugs ability to harm microbes without damaging the host.

• Broad- spectrum : Active against both Gram - positive and Gram - negative bacteria.

• Narrow-spectrum : Effective against specific types of bacteria.

• Bactericidal : Kills bacteria

• Bacteriostatic: Inhibits bacterial growth and reproduction without necessarily killing the bacteria.

History of Chemotherapy

• Paul Ehrlich coined the term chemotherapy and theorized the existence of a "magic bullet" to target pathogens.

• Alexander Fleming discovered penicillin in 1928, noting its ability to inhibit Staphylococcus aureus growth.

• Antibiotics are substances produced by microorganisms to inhibit other microbes' growth.

• Sulfanilamide (sulfa drugs): synthetic drugs effective against bacterial infections were developed following penicillin.

Antibiotic Resistance

• Resistance due to misuse, over-prescription, and genetic mutations in pathogens.

• Notable examples include MRSA (methicillin-resistant Staphylococcus aureus) and multi-drug resistant strains of Pseudomonas aeruginosa.

• Resistance mechanisms include enzymatic destruction, modification of target sites, and increased efflux pumps.

Key Microbial Antibiotics Sources

• Most antibiotics are produced by Streptomyces bacteria.

• Other sources include fungi from the genera Penicillium and Cephalosporium.

Antibiotics and Their Modes of Action

Targeting Cell Wall Synthesis

• Penicillins Blocks peptidoglycan cross- linking, affecting gram-positive bacteria.

• Cephalosporins: broader spectrum; similar mechanism to penicillins.

• Important against penicillin-resistant strains.

Protein Synthesis Inhibition

• Targeting 70S ribosomes; includes:

• Chloramphenicol: inhibits peptide bond formation.

• Aminoglycosides (e.g., gentamicin, streptomycin): alter the ribosomal structure, causing misreading of mRNA.

• Tetracyclines: prevent tRNA attachment, inhibiting peptide chain growth.

• Macrolides (e.g., erythromycin): block the ribosome tunnel, halting protein synthesis.

Injuring Plasma Membranes

• Polymyxin B: disrupts gram-negative bacterial membranes, leading to cell lysis.

• Amphotericin B: antifungal targeting ergosterols in fungal membranes.

Nucleic Acid Synthesis Inhibitors

• Rifampicin: inhibits RNA synthesis, crucial for treating tuberculosis.

• Quinolones: interfere with DNA gyrase, preventing DNA replication.

Competitively Inhibiting Metabolites

• Sulfanilamide: mimics PABA, crucial for bacterial folic acid synthesis.

Spectrum of Antimicrobial Activity

• Narrow-spectrum: effective against specific microbial types.

• Broad-spectrum: affects a wider range, often used when pathogen identity is unknown but can disrupt normal flora, leading to superinfections.

Clinical Considerations

• Importance of determining microbial susceptibility to optimize therapy.

• Various tests:

• Disk diffusion (Kirby-Bauer): assesses sensitivity by measuring zones of inhibition around antibiotic disks.

• Broth dilution tests: determine MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration).

Resistance Mechanisms

• Enzymatic destruction: enzymes (e.g., β-lactamases) degrade antibiotics.

• Alteration of target sites: modified PBPs reduce antibiotic binding efficacy.

• Efflux pumps: actively expel antibiotics, reducing intracellular concentration.

• Mutations: spontaneous genetic changes can confer resistance.

Future Directions in Antimicrobial Research

• Continued search for new antibiotics, focusing on novel microbial sources and mechanisms.

• Investigations into antimicrobial peptides and targeting virulence factors rather than microbes directly.

• Development of new synthetic drugs and exploration of old therapies, like phage therapy, as alternatives.

Antibiotic Safety and Combination Therapy

• Assessing safety (side effects) vs. therapeutic benefits is crucial in prescribing antibiotics.

• Synergism: two drugs working together enhance effectiveness.

• Antagonism: concurrent use of certain antibiotics can decrease their efficacy.

Note: These notes provide an extensive overview of antimicrobial drugs, their functions, historical context, mechanisms of action, antibiotic resistance, and future prospects. Understanding these concepts can help in preparing for related examinations.