Antimicrobial Drugs Notes Chapter 15

Antimicrobial Drugs

Antimicrobial Basics

• Antimicrobials can be:
  • Natural chemicals (e.g., from fungi, Streptomyces).
  • Synthetic chemicals (lab-produced).
  • Semisynthetic chemicals (modified natural chemicals).
• Terminology:
  • Antimicrobial drug: Used internally or topically to treat or prevent infection.
  • Specific types: Antibacterial, antifungal, antiparasitic, antihelminthic, antiprotozoan, antiviral.
• Antibiotic: A natural chemical with activity against bacterial infection.
• Suffixes:
  • -cidal: Kills the microbe (e.g., fungicidal).
  • -static: Inhibits growth but doesn't kill (e.g., bacteriostatic).
• Spectrum:
  • Broad spectrum: Effective against a wide range of microbes.
  • Narrow spectrum: Effective against specific microbes; preferred to minimize microbiome disruption.

Drug Safety and Administration

• Selective toxicity: Target microbe without harming the host.
• Therapeutic index: \frac{\text{maximum safe dose}}{\text{minimum effective dose}}.
• Considerations: Nephrotoxicity, hepatotoxicity.
• Administration: Oral, parenteral, topical.
• Stability & Elimination: Half-life.
• Drug Interactions & Contraindications.

Antibacterial Drug Targets

• Targets include:
  • Cell wall synthesis.
  • Nucleic acid synthesis.
  • Protein synthesis.
  • Folic acid synthesis.
  • Plasma membrane.
• Examples:
  • Cell Wall: Penicillins, Cephalosporins, Carbapenems, Monobactams, Glycopeptides.
  • Nucleic Acids: Quinolones, Rifamycins.
  • Folic Acid: Sulfa drugs, Trimethoprim.
  • Protein: Macrolides, Lincosamides, Phenicols, Tetracyclines, Aminoglycosides
  • Plasma membrane: Polypeptide drugs.

Drugs Against Eukaryotic Microbes

• Antifungal: Target plasma membrane, cell wall, or nucleic acid synthesis.
• Antiprotozoan: Target malarial and non-malarial protozoa.
• Antihelminthic: Interfere with glucose uptake or paralyze the worm.

Antiviral Drugs

• Development is challenging due to the close relationship between viruses and host cells.

Antibiotics and Dysbiosis

• Antibiotics can disrupt the normal microbiome.
• Elimination of key species allows minor species to become dominant and potentially pathogenic (e.g., C. difficile infections, yeast infections).

Superinfections

• Develop when pathogens evolve resistance to antimicrobials.
• "Superbug": A microbe resistant to many or all common antibiotics.
• Examples: Multidrug-resistant tuberculosis (MDR TB), Carbapenem-resistant enterobacteria (CRE).

Antimicrobial Resistance

• Intrinsic Resistance: Natural resistance due to species characteristics.
• Acquired Resistance: Resistance evolved in response to drug presence.
  • Mechanisms: Mutations, horizontal gene transfer (conjugation, transformation, transduction).
  • R plasmids: Transferable plasmids carrying resistance genes.
• Factors Promoting Resistance:
  • Agricultural practices (antimicrobials in animal feed).
  • Unregulated antibiotic use.
  • Noncompliance with prescription dosing.
  • Inappropriate prescriptions.
  • Healthcare settings.

Antimicrobial-Resistant Infections of Concern

• Carbapenem-Resistant Gram-negative infections (CRE).
• Methicillin-Resistant Staphylococcus aureus (MRSA).
• N. gonorrhoeae.
• Tuberculosis (RR/MDR/XDR).
• Malaria.
• Candida auris.
• HIV.

Specific Resistant Organisms

• CRE: Carbapenem-Resistant Enterobacteria (e.g., E. coli, Klebsiella pneumoniae).
  • Carbapenem is a drug of last resort, resistance often plasmid-borne.
• Candida auris: Highly resistant fungus, related to C. albicans, global spread.