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Penicillin
The Ecology of
Antimicrobial Resistance
MDR-TB Hotspots
Antibiotic/Antimicrobial
• Antibiotic: Chemical produced
by a microorganism that kills or
inhibits the growth of another
microorganism
• Antimicrobial agent: Chemical
that kills or inhibits the growth of
microorganisms
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Antimicrobial Agents Disinfection
• Disinfectant: antimicrobial agent • Pasteurization: destruction of all
used only on inanimate objects disease-producing microorganisms
• Chemotherapeutic agent: or reduction in spoilage
antimicrobial agent that can be microorganisms
used internally • Sterilization: killing or removal of all
living organisms and their viruses
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Penicillin Inhibition of
Alexander Fleming
Bacterial Growth
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Penicillin
1942
Microbial
Sources
of
Antibiotics
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Semisynthetic Penicillins
Penicillinase (β Lactamase)
• Penicilinase-resistant penicillins
• Carbapenems: very broad spectrum
• Monobactam: Gram negative
• Extended-spectrum penicillins
• Oral penicillns
• Penicillins + β-lactamase inhibitors
Figure 20.8
Figure 20.9
5
Measuring Antimicrobial Minimal Inhibitory
Sensitivity Concentration
• Antimicrobial
resistance =
increase in MIC
Antimicrobial Resistance in
Biofilms
• 103-104 higher doses needed to kill
biofilm compared with planktonic
organisms
–Biofilm is a molecular filter?
–Low metabolism of cells?
–Reduces drug activity?
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Selection for Resistant Antimicrobial Resistance:
Bacteria Klebsiella pneumoniae
Consequences of
Pseudomembraneous Colitis
Antimicrobial Resistance
• Infections • Normal colon: non spore-forming
resistant to anaerobes predominate
available • Colon after antimicrobial treatment:
antibiotics normal flora reduced
• Increased cost • Clostridium difficile increases
of treatment (Gram + spore-former)
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What Factors Promote Inappropriate Antimicrobial
Antimicrobial Resistance? Use
• Prescription not taken correctly
• Exposure to sub-optimal levels of • Antibiotics for viral infections
antimicrobial
• Antibiotics sold without medical
• Exposure to microbes carrying supervision
resistance genes
• Spread of resistant microbes in
hospitals due to lack of hygiene
Nosocomial Antimicrobial
Resistance
Inappropriate Antimicrobial
Antibiotics in Meat
Use
• Lack of quality control in
manufacture or outdated
antimicrobial
• Inadequate surveillance or
defective susceptibility assays
• Poverty or war
• Use of antibiotics in foods
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Shooting Antibiotics into Cattle Antibiotics in Meat
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Community Associated MRSA Vancomycin Use USA
• MMWR August 22 2003
• Methicillin-resistant Staphylococcus
aureus infections among competitive
sports participants – Colorado, Indiana,
Pennsylvania, and Los Angeles County,
2000-2003
VRE Mortality
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Ecology of Antimicrobial
Resistance
Effects of Combinations of
Effects of Combinations of
Drugs
Drugs
Figure 20.22
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The Future of The Future of
Chemotherapeutic Agents Chemotherapeutic Agents
• Antimicrobial peptides • Antisense agents
– Broad spectrum antibiotics from plants – Complementary DNA or peptide nucleic acids
and animals that binds to a pathogen's virulence gene(s) and
• Squalamine (sharks) prevents transcription
• Protegrin (pigs)
• Magainin (frogs)
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