• Antimicrobial Chemotherapy
• Chemotherapy
• Chemotherapeutic agent (drug)
• Antimicrobial agent
• Antibiotic
• Synthetic drug
• Semisynthetic drug
• History
• Ancient Egypt – Moldy bread compresses for wounds.
Penicillin grows on bread
• Ancient Greece – Honey as a wound infection preventative.
Hypertonic solution
• Middle Ages & Renaissance (post-fall of Roman Empire ~530 A.D. – 1600 A.D.) – Largely
continuation of classical medicine which included medicinal plants/extracts (think Historia
Plantarum and Naturalis Historia) with some magic thrown in.
• 1619 A.D. – First recorded malaria cure using cinchona bark extract (quinine).
• ~1680 A.D. – Ipecacuanha used to treat “bloody flux”.
- important to Paris; bloody diarrhea; used in small amounts; higher doses poison
(vomiting)
- Repeated use can damage coordinate muscles
- Karen Ann Carpenter
• 1909 A.D. – Salvarsan developed and marketed by Paul Erlich.
Arsenic based: marketed for treating syphilis
• 1929 A.D. – Alexander Fleming discovers penicillin but doesn’t publish until 1940.
• 1932 A.D. – Protosil, the first sulfinlimide, is discovered.
- inhibits bacteria from making peptidoglycan
• Antimicrobial Agents – General Properties
• Selective toxicity – Killing of thee and not of me.
• Spectrum of Activity – Broad or narrow?
• Modes of Action – What, specifically, does it do?
• Side Effects – Both direct and indirect.
• Microbial resistance – All flesh is grass.
• Selective toxicity
• All antimicrobial agents have it.
• Some are too toxic to take internally.
Neosporin: too toxic
• Gap between Therapeutic <----> Toxic
• Chemotherapeutic index
Max tolerable dose/kg
Min dose to cure/kg
• The greater the similarity between host and parasite, the lower the index.
• Worms vs. Fungi vs. Bacteria
• Spectrum of Activity
• The range of microbes against which an antimicrobial agent works.
, • Broad Spectrum
• Narrow Spectrum
• Modes of Action
• Not all of them are well understood.
• Antimicrobials can kill or slow down invaders but the host’s immune system does the
elimination.
• 5 Basic types:
• Inhibition of cell wall synthesis
• Disruption of membrane function
• Inhibition of protein synthesis
• Inhibition of nucleic acid synthesis
• Antimetabolic activity.
• Side Effects
• Direct
• Toxicity
• Allergy
• Indirect
• Disruption of microflora
• Resistance is… Inevitable.
• Can be biochemical, locational, or based on phenotypic plasticity.
• Chromosomal or extrachromosomal.
• Mechanisms
• Alteration of target
• Alteration of membrane permeability
• Development of enzymes
• Alteration of an enzyme
• Alteration of metabolic pathway
• Cross-resistance
• Human Responses to Microbial Resistance
• Case Study: Gonorrhea
- urogenital, systemic, ocular, cutaneous cases
- Has been around for a long time (Ancient Greece)
• First line: Sulfonamide (1930’s)
• Second line: Penicillin (1940’s)
• 2.5 line: MORE PENICILLIN! (1965)
• Third line: Spectinomycin (1970’s)
• Fourth line (right now): Ceftriaxone (injection ) with Azithromycin or doxycycline (oral)
Limiting the Spread
• High doses
• Combination
• Add silver
• Restrict use
• Quorum Sensing: won’t cause disease unless they reach high enough concentration
• Chemotherapy
• Chemotherapeutic agent (drug)
• Antimicrobial agent
• Antibiotic
• Synthetic drug
• Semisynthetic drug
• History
• Ancient Egypt – Moldy bread compresses for wounds.
Penicillin grows on bread
• Ancient Greece – Honey as a wound infection preventative.
Hypertonic solution
• Middle Ages & Renaissance (post-fall of Roman Empire ~530 A.D. – 1600 A.D.) – Largely
continuation of classical medicine which included medicinal plants/extracts (think Historia
Plantarum and Naturalis Historia) with some magic thrown in.
• 1619 A.D. – First recorded malaria cure using cinchona bark extract (quinine).
• ~1680 A.D. – Ipecacuanha used to treat “bloody flux”.
- important to Paris; bloody diarrhea; used in small amounts; higher doses poison
(vomiting)
- Repeated use can damage coordinate muscles
- Karen Ann Carpenter
• 1909 A.D. – Salvarsan developed and marketed by Paul Erlich.
Arsenic based: marketed for treating syphilis
• 1929 A.D. – Alexander Fleming discovers penicillin but doesn’t publish until 1940.
• 1932 A.D. – Protosil, the first sulfinlimide, is discovered.
- inhibits bacteria from making peptidoglycan
• Antimicrobial Agents – General Properties
• Selective toxicity – Killing of thee and not of me.
• Spectrum of Activity – Broad or narrow?
• Modes of Action – What, specifically, does it do?
• Side Effects – Both direct and indirect.
• Microbial resistance – All flesh is grass.
• Selective toxicity
• All antimicrobial agents have it.
• Some are too toxic to take internally.
Neosporin: too toxic
• Gap between Therapeutic <----> Toxic
• Chemotherapeutic index
Max tolerable dose/kg
Min dose to cure/kg
• The greater the similarity between host and parasite, the lower the index.
• Worms vs. Fungi vs. Bacteria
• Spectrum of Activity
• The range of microbes against which an antimicrobial agent works.
, • Broad Spectrum
• Narrow Spectrum
• Modes of Action
• Not all of them are well understood.
• Antimicrobials can kill or slow down invaders but the host’s immune system does the
elimination.
• 5 Basic types:
• Inhibition of cell wall synthesis
• Disruption of membrane function
• Inhibition of protein synthesis
• Inhibition of nucleic acid synthesis
• Antimetabolic activity.
• Side Effects
• Direct
• Toxicity
• Allergy
• Indirect
• Disruption of microflora
• Resistance is… Inevitable.
• Can be biochemical, locational, or based on phenotypic plasticity.
• Chromosomal or extrachromosomal.
• Mechanisms
• Alteration of target
• Alteration of membrane permeability
• Development of enzymes
• Alteration of an enzyme
• Alteration of metabolic pathway
• Cross-resistance
• Human Responses to Microbial Resistance
• Case Study: Gonorrhea
- urogenital, systemic, ocular, cutaneous cases
- Has been around for a long time (Ancient Greece)
• First line: Sulfonamide (1930’s)
• Second line: Penicillin (1940’s)
• 2.5 line: MORE PENICILLIN! (1965)
• Third line: Spectinomycin (1970’s)
• Fourth line (right now): Ceftriaxone (injection ) with Azithromycin or doxycycline (oral)
Limiting the Spread
• High doses
• Combination
• Add silver
• Restrict use
• Quorum Sensing: won’t cause disease unless they reach high enough concentration
