Antimicrobial Treatments Overview

Overview

This lecture covered antimicrobial treatments, focusing on antibiotics, their history, mechanisms of action, resistance, and alternative therapies.

No perfect drug exists; all have pros/cons, including side effects and resistance risk.
Ideal drugs are toxic to microbes, not host; microbicidal (kill microbes), not just microbistatic (inhibit growth).
Soluble in body fluids, remain potent long enough, and resist early excretion.
Low potential for developing resistance; do not disrupt host health or immune defenses.
Able to reach infection site easily with minimal side effects.

Antibiotics target bacteria; antimicrobials may also target fungi or protozoa.
Narrow spectrum: targets specific microbes; broad spectrum: affects wide range.
Natural sources: mainly fungi (e.g., penicillin from Penicillium) and other bacteria.
Synthetic and semisynthetic antibiotics are lab-made or modified from natural sources.

Penicillin discovered by Alexander Fleming in 1928; Nobel Prize awarded in 1945.
Originated from observing bacterial inhibition by mold on contaminated plates.

Doctors consider causative organism, drug susceptibility (Kirby-Bauer test), and patient health before prescribing.
Kirby-Bauer disc diffusion test uses Mueller-Hinton agar to measure zones of inhibition (sensitivity/intermediate/resistant).

Selective toxicity: the drug harms microbes, not the host; higher therapeutic index (TI) means safer drug.
Drugs are less selective and have more side effects when targeting structures similar to host cells.

Cell wall synthesis inhibitors (e.g., penicillin, bacitracin) target peptidoglycan—unique to bacteria.
Protein synthesis inhibitors (e.g., aminoglycosides, tetracyclines, macrolides) target ribosomes.
Folic acid synthesis inhibitors (e.g., sulfonamides) block bacterial nucleotide production.
Cell membrane disruptors (e.g., polymyxins) break up bacterial membranes; more side effects due to similarity with human cells.
Nucleic acid synthesis inhibitors (e.g., ciprofloxacin, nalidixic acid) block DNA/RNA replication.

Resistance through spontaneous mutation or horizontal gene transfer (conjugation, transformation, transduction).
Mechanisms: drug-inactivating enzymes (e.g., beta-lactamases), reduced uptake, drug efflux, altered targets, alternative pathways.
Resistance began soon after antibiotics were first discovered; now a major health crisis (e.g., MRSA, XDR Klebsiella).

Prescribe antibiotics appropriately; take full course; limit over-the-counter access.
Develop drugs targeting specific virulence factors and use combination therapies.
Alternative approaches: CRISPR-Cas9 gene editing, bacteriophage therapy, probiotics (live bacteria), prebiotics (food for beneficial bacteria), fecal transplants, anti-quorum sensing molecules.

Antibiotics can disrupt normal flora; may cause superinfections (e.g., C. difficile).
Fecal transplants can cure recurrent C. difficile within one day.
Damage to microbiome can also cause yeast infections and other issues.

Selective Toxicity — Drug targets microbes without harming host cells.
Therapeutic Index (TI) — Ratio indicating drug safety; higher is safer.
Kirby-Bauer Test — Disc diffusion method to assess antibiotic susceptibility.
Beta-lactamase — Enzyme that breaks down beta-lactam antibiotics.
Probiotic — Live beneficial bacteria taken to support microbiome.
Prebiotic — Non-digestible food promoting beneficial microbe growth.
Superinfection — New infection caused by disruption of normal flora during treatment.

Review antibiotic categories and their mechanisms.
Memorize five main antibiotic targets and key examples.
Study Kirby-Bauer test protocol and interpretation.
Know the difference between probiotics and prebiotics.
Read assigned textbook sections on antimicrobial resistance and alternative therapies.