Antimicrobials

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Antimicrobials

• Antibiotics The Biological Weapons of Choice
  for Microorganisms!

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Outline

• Antimicrobial basics
• Terminology
• Measuring activity
• Resistance factors
• Chemotherapeutic Agents
• Spectrum
• Selective Toxicity
• Varieties
• Antibiotics
• Various types (antibacterial and antiviral)
• Mechanisms of action
• Spectrum
• Selective toxicity
• Target
• Resistance

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Chemical Antimicrobial Agents

• Cidal versus static
• Remove agent and __________
• Permanent binding versus temporary
• Bacterio, fungi, viri
• Lytic
• Measuring activity
• MIC
• Affects on it
• Organism, inoculum size, OM, incubation time,
  conditions
• Standardize
• Phenol Coefficient Standard

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MIC
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Chemical Antimicrobial Agents

• Measuring Activity continued
• Agar Diffusion (Kirby Baur)
• MICzone of inhibition
• Affects include amount of inoculum, concentration
  of agent, diffusion coefficient solubility of
  agent, incubation time and conditions
• Standardize variables

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Chemotherapeutic Agents

• In vivo
• Oral, intravenous, anal
• Selective toxicity issues
• Synthetic versus antibiotic
• Spectrum of Activity
• Antibiotics
• Who?
• Where?

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Antibiotics

• Naturally occurring
• Fungi and Bacteria
• Actinomycetes, Bacillus
• Many in soil not many used
• Selective toxicity
• Less than 1 clinically useful

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Spectrum

• 20.15

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Quinolones (nalidixic acid) and Fluoroquinolones
(ciprofloxacin)

• Synthetic chemotherapeutic agent
• Bacteriocidal
• Broad spectrum
• Bacterial DNA gyrase inhibitors
• Topoisomerase II (Gram negative)
• Topoisomerase IV (Gram-positive)
• Interferes with _____________.
• Quinolone resistance
• Modify the target (ser83trp)

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DNA Gyrase

• DNA Gyrase
• Cause Negative supercoils
• Relax positive supercoils

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Aminoglycosides

• Amino sugar10Amino sugar2
• Aerobic Gram negative bacilli and mycobacteria
• Bacteriocidal in Gram negative
• S. griseus and Streptomycin
• Danamycin, neomycin, gentamycin
• Inhibits _______ synthesis
• 30S ribosome
• Why not static?
• Membrane fissures in Gram negative cells
• Not many used today
• Toxicity, nephrotoxicity (renal cortical
  accumulation in tubular cells), ototoxicity
  (accumulation in inner ear)
• Resistance via enzyme inactivation

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Aminoglycoside Action and Resistance
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Macrolides

• Macrolide ring
• Bacteriostatic
• Inhibit _______ synthesis
• 50S ribosome
• Gram positive, Mycobacteria, Rickettsia and
  chlamydia, Legionella
• Erythromycin
• Mechanism
• Patients allergic to pcn
• Macrolide resistance
• Modification of 23S rRNA so erythromycin cannot
  bind

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Macrolide Mechanism
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Tetracyclines

• Structure
• Naphthacene ring
• Bacteriostatic
• Streptomyces spp.
• First broad spectrum
• Inhibit ______ synthesis
• 30S ribosome
• Oxytetracycline and Chlortetracycline
• Used in veterinary industry a lot
• Tooth discoloration
• Prion diseases

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Tetracycline Mechanism
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Chloramphenicol

• Bacteriostatic
• Streptomyces venezuelae
• Inhibit _______ synthesis
• 50S ribosome
• Inhibits tRNA binding to A site
• 1949 first synthetically mass produced
  antibiotic
• Side effects aplastic anemia
• Conjunctivitis
• Eye ointment

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Antiviral Drugs

• Selective Toxicity
• Targets
• Nucleic acid mainly
• Enzymes
• Binding, uncoating, invasion
• Most drugs geared to HIV
• Nucleoside analogs
• NRTI
• NNRTI
• Protease inhibitors
• Fusion inhibitors

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HIV Life Cycle
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Protease and Fusion Inhibitors
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Influenza

• Synthetic amines (rimantadine)
• Uncoating

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Influenza Virus

• Neuraminidase inhibitors
• Oseltamivir or zanamivir

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Resistance to Antimicrobials

• Endospore
• Gram positive versus Gram negative
• Capsule
• Mycobacteria
• Hepatitis
• Cysts (helminths)
• Metabolic bypass
• Resistance factors on plasmids
• Efflux pump
• Inactivate drug
• Modify target

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Resistance

• Resistance predates the use of the drugs
• Why natural resistance exists
• Strains that make the antibiotic
• Defense in natural environment
• Why resistance spread
• Increased drug use and natural selection
• Horizontal gene transfer and natural selection

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Problems

• Why
• Improper use by physicians
• Patient noncompliance
• Agriculture food supplements and growth promoters
• Prophylactic treatment
• MRSA
• VRE
• VISA

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Reducing the Problem

• Drug combinations
• Right dosing
• Right time line
• Educating patients
• Educating consumers and farmers