Chapter 10

• Drugs: Chemicals that affect Physiology in any manner
• Chemotherapeutic agents: Drugs that act against diseases
• Antimicrobial agents: Drugs that treat infections
• Antibiotics: Antimicrobial agents that are produced naturally by an organism
• Semisynthetic antimicrobials: Chemically altered antibiotics
• Synthetic antimicrobials: Lab-synthesized antimicrobial
• Selective toxicity: a drug that is selectively toxic to certain cells or tissues
• Mechanisms of Action: Inhibit cell wall synthesis

  – Inhibit protein synthesis

  – Disrupt unique components of cell membrane

  – Inhibit general non-human metabolic pathways

  – Inhibit nucleic acid (DNA/RNA) synthesis

  – Block pathogen’s recognition/attachment mechanisms
• Ideal antimicrobial agents are: Inexpensive, Readily available, Easily administered, chemically stable, nontoxic and nonallergenic and selectively toxic.
• Spectrum of Action: Number of different pathogens a drug acts against
• Narrow-spectrum: Effective against few organisms
• Broad-spectrum: Effective against many organisms
• Routes of administration: Topical, oral, Intramusclar, and Intravenous
• Ways to test of effectiveness of microbial drugs: Kirby-Bauer, MIC, E-test and MBC test
• Safety and side effects of antimicrobials: Toxic to kidneys, liver, or nerves
• Therapeutic index: Ratio of the dose of a drug that can be tolerated to the drugs effective dose
• Allergies to antimicrobials can cause anaphylactic shock
• Antimicrobials can cause disruption of normal microbiota Which can result in secondary infections
• R plasmids: Helps microbes have resistance to anti-microbials
• Persister cells: Same genome, more resistance
• Urgent: Potential for widespread life-threatening disease
• Serious: Alternative antimicrobials are available or disease incidence is low or declining
• Concerning: Low threat or numerous antimicrobials are available for treatment
• Mechanisms of Resistance:Mechanisms of Resistance

  ▪ Produce enzyme that destroys or deactivates drug ▪ Slow or prevent entry of drug into the cell

  ▪ Alter target of drug so it binds less effectively

  ▪ Alter their own metabolic chemistry

  ▪ Pump antimicrobial drug out of the cell before it can act ▪ Bacteria in biofilms can resist antimicrobials

  ▪ Mycobacterium tuberculosis produces MfpA protein

  –Binds DNA gyrase, preventing the binding of fluoroquinolone drugs
• Multiple-drug resistant pathogens: Resistant to at least three antimicrobial agents
• Cross resistance: Can occur when drugs are similar in structure
• Synergism: Occurs when one drug enhances the effect of a second drug
• Antagonism: Occurs when drugs interfere with each other