Antimicrobial Drugs Study Notes

ANTIMICROBIAL DRUGS

Bacteriostatic Drugs

  • Definition: Drugs that cause a reversible inhibition of bacterial growth.
  • Effect: Bacterial growth resumes after the discontinuation of the drug.

Bactericidal Drugs

  • Definition: Drugs that kill target bacteria.
  • Usage: Generally preferred when need for rapid reduction of bacterial load is critical.

Spectrum of Activity

  • Narrow-Spectrum Antimicrobial Drug:
    • Targets: Specific subsets of bacterial pathogens (e.g., only Gram-positive or only Gram-negative bacteria).
  • Broad-Spectrum Antimicrobial Drug:
    • Targets: A wide variety of bacterial pathogens (includes both Gram-positive and Gram-negative bacteria).
    • Usage: Frequently used as empiric therapy before lab identification of infecting pathogens.

Superinfection

  • Definition: A secondary infection that develops when broad-spectrum antimicrobials eliminate protective normal flora, allowing antibiotic-resistant pathogens to proliferate.
  • Examples:
    • Yeast Infections: Candidiasis.
    • Pseudomembranous Colitis: Caused by Clostridium difficile; can be fatal.

Selective Toxicity

  • Concept: Antimicrobial drugs selectively kill or inhibit growth of microbial targets while minimizing harm to the host.

Mechanisms of Antibacterial Drugs

  • Modes of Action:
    1. Inhibit cell wall biosynthesis.
    2. Inhibit protein biosynthesis.
    3. Disrupt membranes.
    4. Inhibit nucleic acid synthesis.
    5. Act as antimetabolites.
    6. Inhibit mycobacterial ATP synthase.

Inhibit Cell Wall Biosynthesis

  • Targets:
    • Penicillin-binding proteins.
  • Drug Classes:
    • β-lactams: penicillins, cephalosporins, monobactams, carbapenems.
    • Glycopeptides: Target peptidoglycan subunits.
    • Bacitracin: Targets peptidoglycan subunit transport.

Inhibit Protein Biosynthesis

  • 30S Ribosomal Subunit: Targeted by aminoglycosides, tetracyclines.
  • 50S Ribosomal Subunit: Targeted by macrolides, lincosamides, chloramphenicol, oxazolidinones.

Disrupt Membranes

  • Targets: Lipopolysaccharide, inner and outer membranes.
  • Drug Classes: Polymyxin B, Colistin, Dapromycin.

Inhibit Nucleic Acid Synthesis

  • Targets: RNA and DNA.
  • Drug Classes: Rifamycin (RNA), fluoroquinolones (DNA).

Antimetabolites

  • Targets: Folic acid synthesis enzymes and mycolic acid synthesis enzymes.
  • Drug Classes: Sulfonamides, trimethoprim; isonicotinic acid hydrazide.

Mycobacterial ATP Synthase Inhibitor

  • Targets: Mycobacterial ATP synthase.
  • Drug Class: Diarylquinoline.

Antimicrobial Drug Resistance

  • Problem: Rising due to selection of drug-resistant strains, misuse of drugs, subtherapeutic dosing, and poor patient compliance.

Drug Resistance Genes

  • Location: Often found on plasmids or in transposons.

Modes of Antimicrobial Drug Resistance

  1. Drug Modification or Inactivation:

    • Resistance genes can code for enzymes that chemically modify the drug, rendering it inactive.
    • Example: Hydrolysis of the β-lactam bond, leading to loss of antibacterial activity.

  2. Prevention of Cellular Uptake or Efflux:

    • Mechanisms inhibit drug accumulation inside the cell.
    • Example: Active efflux of drugs like β-lactams and tetracyclines out of the cell.

  3. Target Modification:

    • Changes in target structures prevent drug binding.
    • Examples:
      • Alterations in ribosome subunits can confer resistance to macrolides.
      • Alterations in LPS structure provide resistance to polymyxins.

  4. Target Overproduction or Enzymatic Bypass:

    • Microbes may overproduce target enzymes or develop bypass pathways.
    • Example: Vancomycin resistance in S. aureus causes decreased cross-linking in the cell wall, increasing binding targets for the antibiotic.

  5. Target Mimicry:

    • Microbes produce proteins that mimic drug binding sites, sequestering drugs.
    • Example: M. tuberculosis produces a protein that binds fluoroquinolones, preventing them from targeting DNA.

Administering Antimicrobial Therapies

  • Factors to Consider:
    • Correct diagnosis.
    • Renal function.
    • Hepatic function.
    • Age considerations: pediatric (guided by weight), geriatric (creatinine clearance).
    • Pregnancy and lactation status.
    • History of allergies or intolerances.
    • Recent antimicrobial use history.
    • Cost considerations (IV vs. oral therapy).
    • Preferential use of narrow-spectrum agents.
    • Shortest duration of therapy possible to avoid resistance.