MC3 LEC

• Chemotherapeutic agent


  Any drug used to treat any condition or disease
• Antimicrobial agent


  Chemotherapeutic agents used to treat infectious diseases either by inhibiting or by killing pathogens in vivo
• Types of antimicrobial agents

  • Antibacterial agents
  • Antifungal agents
  • Antiprotozoal agents
  • Antiviral agents
• Antibiotic


  A substance produced by a microorganism that is effective in killing or inhibiting the growth of other microorganisms
• "All antibiotics are antimicrobial agents, not all antimicrobial agents are antibiotics"

  
• Characteristics of an ideal antimicrobial agent

  • Kill or inhibit the growth of pathogens
  • Cause no damage to the host
  • Cause no allergic reaction in the host
  • Be stable when stored in solid or liquid form
  • Remain in specific tissues in the body long enough to be effective
  • Kill the pathogens before they mutate and become resistant to it
• Antimicrobial mechanism of action

  • Inhibition of cell wall synthesis
  • Damage to cell membranes
  • Inhibition of nucleic acid synthesis (either DNA or RNA synthesis)
  • Inhibition of protein synthesis
  • Inhibition of enzyme activity
• Bacteriostatic drugs


  Inhibit bacterial growth, e.g. sulfonamide drugs that inhibit production of folic acid

  
• Bactericidal drugs


  Kill the bacteria, e.g. penicillin that interferes with the synthesis and cross-linking of peptidoglycan in bacterial cell walls
• Spectrum of antibiotic action

  • Narrow-spectrum (kill either Gram-positive or Gram-negative bacteria)
  • Broad-spectrum (destroy both Gram-positive and Gram-negative bacteria)

  
• Major categories of antibacterial agents

  • B-lactam rings (inhibit synthesis of bacterial cell walls)
  • Sulfonamide drugs (interfere with synthesis of folic acids)
  • Aminoglycosides (inhibit translation of mRNA)

  
• Specific classification of antibacterial drugs

  • Penicillins (B-lactam drugs)
  • Cephalosporins (B-lactam drugs)
  • Carbapenems
  • Glycopeptides
  • Aminoglycosides
  • Macrolides
  • Fluoroquinolones
• Multidrug therapy


  Use of two or more drugs simultaneously to kill all the pathogens and to prevent resistant mutant pathogens from emerging
• Synergism


  Use of two antimicrobial agents produces a degree of pathogen killing far greater than either drug alone
• Antagonism


  Use of two antimicrobial agents produces a degree of pathogen killing less than either drug alone
• Combined effects of drugs

  • No interaction
  • Increased effect (summation, additive, synergism)
  • Decreased effect (antagonism)

  
• Drug resistance "superbugs"


  Multidrug resistant organisms that are resistant to more than one antimicrobial agent, much more difficult to treat
• How bacteria become resistant to drugs

  • Intrinsic resistance (lack specific target site)
  • Acquired resistance (once susceptible become resistant)

  
• Mechanisms of bacterial resistance

  • Target modification
  • Blocked penetration
  • Inactivation by enzymes
  • Prevention of cellular uptake or efflux

  
• Factors that accelerate evolution of drug resistance include overuse and misuse of antimicrobials, inappropriate use, sub-therapeutic dosing, and patient noncompliance
• Strategies against drug resistance

  • Patients must take antibiotics as prescribed and complete the full course
  • Patients should destroy any excess medications and not keep antibiotics in medicine cabinet
• Empiric therapy


  Best "informed guess" therapy before pathogen is identified, based on most likely infecting organism
• Definitive therapy


  Therapy optimized for narrower coverage after infective organism is identified and sensitivities tested
• Pathogenesis


  Initiation of the infectious process and the mechanisms that lead to development of signs and symptoms of disease

  
• Characteristics of bacterial pathogens

  • Transmissibility
  • Adherence to host cells
  • Persistence
  • Invasion of host cells and tissues
  • Toxigenicity
  • Ability to evade or survive the host's immune system
• Aspects of pathogenesis


  • Adherence
  • Carrier
  • Infection
  • Invasion
  • Microbiota
  • Nonpathogen
  • Opportunistic pathogen
  • Pathogen
  • Pathogenicity
  • Toxigenicity
  • Virulence

  
• Virulence


  The quantitative ability of an agent to cause disease, involving adherence, persistence, invasion, and toxigenicity
• Virulence factors


  • Capsule
  • Spores
  • Pili
  • Flagella
  • Exoenzymes
• When pathogens enter the body

  1. The organisms strive to invade the tissues and colonize there

  2. The body's defenses strive to block the invasion of microbes, destroy them and cast them off
• Virulence


  The organism's capacity to cause disease, affected by resistance to antimicrobials and disinfectants
• To express or measure the degree of pathogenicity


  Disease occurs if the bacteria or immunologic reactions to their presence cause sufficient harm to the person

  
• Virulence Factors


  • Capsule - Anti-phagocytic function
  • Spores - additional protection
  • Pili - enable bacteria to attach to surfaces
  • Flagella - bacteria to invade aqueous areas of the body
  • Exoenzymes
  • Toxins

  
• Exotoxin


  Proteins produced inside the pathogenic bacteria, most commonly g+ bacteria and or g-, as part of their growth and metabolism. The exotoxins are then secreted or released into the surrounding medium following lysis.

  
• Types of Exotoxin


  • Neurotoxin – interferes with normal nerve impulse transmission
  • Enterotoxin – affects cell lining of the GI tract
  • Exfoliative - causes epidermal layers of the skin to slough away
  • Cytotoxin – kills the host cells or affects the function
  • Leukocidins – destroys leukocytes or WBCs such neutrophils and macrophages

  
• Endotoxin


  The lipid portions of lipopolysaccharides (LPSs) that are part of the outer membrane of the cell wall of G- bacteria. The endotoxins are liberated when the bacteria die and the cell wall breaks apart.

  
• Other Virulence Factors


  • Necrotizing Factor - causes the death of body cells
  • Hypothermic Factor - decreases body temperature
  • Siderophores - which scavenge iron from the host's body fluids
  • M Protein - (component of cell wall) mediates attachment of the bacterium
• Classification of Diseases by Area of Invasion

  • Localized – invading pathogens are limited to small areas of the body or a the original site of infection
  • Generalized/systemic – pathogens spread throughout the body by blood or lymph
  • Latent –pathogens remain inactive for a time but become active to produce symptoms of the disease

  
• Classification of Diseases by Severity or Duration

  • Acute disease – one that develops rapidly but lasts only a short time
  • Subacute Disease - sudden onset less than acute but develops into long lasting disease
  • Chronic disease – develops more slowly and lasts a long time
• Classification of Diseases by Manner of Reaching the Body


  • Communicable disease
  • Non communicable disease

  
• Classification of Diseases by Frequency of Occurrence

  • Sporadic disease
  • Endemic disease - transmission occurs, but the number of cases remains constant
  • Epidemic disease - the number of cases increases in specific area
  • Pandemic disease - epidemic occurs at several continents (global epidemic)