Lecture 2 - Bacteriology - Antibiotics

Antimicrobial Agents

• Disinfectants:

  • Antimicrobial agents used on inanimate objects (e.g., floors, tables).

• Antiseptics:

  • Antimicrobial agents safe for application to living tissues (e.g., hand sanitizers).

• Antibiotics:

  • Natural antimicrobial agents produced by bacteria and fungi exploited for therapy; can be delivered topically or systemically.

Importance of Antibiotics

• Therapeutic Role:

  • Crucial for treating bacterial infections and enabling advanced medical practices such as cancer chemotherapy, organ transplants, and invasive surgeries.

• Challenges:

  • Diminished pharmaceutical interest in developing new antibiotics.

  • Constant emergence of bacterial resistance.

Antibiotic Deployment Timeline

• Historical deployment of various antibiotics and emergence of resistance observed:

  • Timeline from 1930 to present highlighting key antibiotics (e.g. Penicillin, Tetracycline, Vancomycin).

Misuse of Antibiotics

• Causes of Increased Resistance:

  • Empiric use and reliance on broad-spectrum agents.

  • Misuse in pediatric cases for viral infections.

  • Non-compliance in completing antibiotic courses.

  • Use in animal feeds contributes to resistance.

Measuring Antibiotic Activity

• Minimum Inhibitory Concentration (MIC):

  • Defined as the lowest concentration of an antibiotic required to inhibit bacterial growth; assessed through serial dilution methods.

Mechanism of Action of Antibiotics

• Targets of Antibiotics:

  • Inhibition of bacterial processes:

    • Cell wall synthesis

    • Protein synthesis

    • DNA/RNA synthesis

    • Folate synthesis

    • Cell membrane integrity

  • Distinct targets in prokaryotic cells, unlike eukaryotic cells.

β-Lactam Antibiotics

• General Functionality:

  • Contain a β-lactam ring essential for inhibiting cell wall synthesis.

  • Target penicillin-binding proteins (PBPs), crucial for maintaining a stable cell wall structure; some bacteria evolve β-lactamases to counteract this effect.

Resistance Mechanisms in Bacteria

• Vancomycin:

  • Works via binding to D-Ala-D-Ala peptide linkages; resistance evolves through modification of these links to entail D-Ala-D-Lac.

• Resistance Strategies:

  • Prevention of antibiotic entry

  • Antibiotic modification via enzymes (like β-lactamase)

  • Efflux mechanisms to pump antibiotics out

  • Alteration of target sites or bypassing actions of antibiotics.

Antibiotic Resistance Genes

• Resistance often genetically encoded, with high levels encoded on mobile elements like plasmids facilitating horizontal gene transfer, contributing to the emergence of 'superbugs'.

Major Antibiotic Resistant Threats (CDC)

• Serious Threats:

  • Multidrug-resistant Acinetobacter, VRE, MRSA, Drug-resistant Tuberculosis, and more.

• Urgent Threats:

  • Clostridioides difficile and Carbapenem-resistant Enterobacteriaceae (CRE).

Clostridia Overview

• Clusters of Significance:

  • Includes Clostridium perfringens, C. difficile, et al.

  • Noteworthy for causing severe diseases via exotoxins.

Clostridioides difficile (C. diff)

• Associated with various states from asymptomatic carrier to severe pseudomembranous colitis.

• Predominantly culprit in nosocomial infections, with fecal-oral transmission routes facilitating spread.

Pseudomembranous Colitis

• Symptoms & Diagnosis:

  • Characterized by abdominal pain, diarrhea, and fever, often appearing shortly after or even weeks following antibiotic treatment.

Treatment Strategies for C. difficile Infection

• Discontinuation of the inciting antibiotic, supportive care, and targeted therapy, including options like vancomycin.

• Avoidance of antidiarrheal agents recommended.

Fecal Microbiota Transplantation (FMT)

• Potential innovative treatment for recurrent C. difficile infections, restoring gut microbiota through various methods, showing promising results in clinical trials.