抗生素PPT课件(英文精品) Resistance to antibiotics
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• e.g. sulfonamide resistance if high purines, methionine, thymidine available (such as in an abscess)
• e.g. aminoglycosides not effective in anaerobic environment
There are 7.5 billion chickens, 292 million turkeys, 109 million cattle and 92 million pigs in the United States.
Antibiotics given to pigs as of 2000
Plasmid-mediated drug resistance
tetracycline sulfonamide
chloramphenicol aminoglycoside
Problems with Antibiotic resistance
➢ more than 50% of antibiotics used in domestic animals for subtherapeutic effect: breeding ground for resistance
➢ “KFC does not purchase poultry treated nontherapeutically with medically important antibiotics.” – Letter to “Keep Antibiotics Working,” August 28, 2002
why? doesn’t get in---weaken barrier with amphotericin and then it does
• isoniazid does not kill bugs that don’t require synthesis of mycolic acids
➢ Environmental resistance
Resistance to antibiotics
➢ Intrinsic resistance (examples)
• penG does not enter gram negative bacteria well
why? doesn’t penetrate--ampicillin does
• rifampin doesn’t kill fungi
resistance, vancomycin resistance, ciprof来自百度文库oxacin res.)
Vancomycin resistance: mechanism
Vancomycin resistance: mechanism
Resistance can be transferred between bacteria
Drug export systems in Gram +
Acquired Drug Resistance
➢1. enzymatic inactivation (b-lactams, aminoglyc. chloramph) ➢2. rapid efflux of drug out of cell (tetracyclines, ciprofloxacin)
➢ McDonald’s ‘We’ve listened to the concerns, studied the issue, and the bottom line was we thought it was the right thing to do to discontinue the use of [fluoroquinolone antibiotics] in poultry,’ said Walt Riker, spokesman for Oak Brook-based McDonald’s. – Walt Riker, McDonald’s, “Chickens Fed With Antibiotics McGone,” Chicago Sun-Times, February 12, 2002
➢ Acquired Resistance
• genetic changes, plasmids with new genes
Bacteria keep up with big pharma in the b-lactam antibiotic arms race
bacteria can often express more than one b-lactamase
➢3. decreased conversion to active form (isoniazid) ➢4. increased concentration of antagonist/competitor (sulfonamide
resistance with increased PABA synthesis). ➢5. altered amount of receptor (trimethoprim-DHFR amplification) ➢6. altered structure of target to reduce binding (methicillin
Inactivation of aminoglycosides by acetylation, phosphorylation, and adenylation in drugresistant organisms
Acquired Drug Resistance
➢1. enzymatic inactivation (b-lactams, aminoglyc. chloramph) ➢2. rapid efflux of drug out of cell (tetracyclines, ciprofloxacin)
➢ phage transduction ➢ transposable elements ➢ plasmid transfer during conjugation
• plasmids can contain multiple resistance genes • transfer can occur between non-pathogen and pathogens
• e.g. aminoglycosides not effective in anaerobic environment
There are 7.5 billion chickens, 292 million turkeys, 109 million cattle and 92 million pigs in the United States.
Antibiotics given to pigs as of 2000
Plasmid-mediated drug resistance
tetracycline sulfonamide
chloramphenicol aminoglycoside
Problems with Antibiotic resistance
➢ more than 50% of antibiotics used in domestic animals for subtherapeutic effect: breeding ground for resistance
➢ “KFC does not purchase poultry treated nontherapeutically with medically important antibiotics.” – Letter to “Keep Antibiotics Working,” August 28, 2002
why? doesn’t get in---weaken barrier with amphotericin and then it does
• isoniazid does not kill bugs that don’t require synthesis of mycolic acids
➢ Environmental resistance
Resistance to antibiotics
➢ Intrinsic resistance (examples)
• penG does not enter gram negative bacteria well
why? doesn’t penetrate--ampicillin does
• rifampin doesn’t kill fungi
resistance, vancomycin resistance, ciprof来自百度文库oxacin res.)
Vancomycin resistance: mechanism
Vancomycin resistance: mechanism
Resistance can be transferred between bacteria
Drug export systems in Gram +
Acquired Drug Resistance
➢1. enzymatic inactivation (b-lactams, aminoglyc. chloramph) ➢2. rapid efflux of drug out of cell (tetracyclines, ciprofloxacin)
➢ McDonald’s ‘We’ve listened to the concerns, studied the issue, and the bottom line was we thought it was the right thing to do to discontinue the use of [fluoroquinolone antibiotics] in poultry,’ said Walt Riker, spokesman for Oak Brook-based McDonald’s. – Walt Riker, McDonald’s, “Chickens Fed With Antibiotics McGone,” Chicago Sun-Times, February 12, 2002
➢ Acquired Resistance
• genetic changes, plasmids with new genes
Bacteria keep up with big pharma in the b-lactam antibiotic arms race
bacteria can often express more than one b-lactamase
➢3. decreased conversion to active form (isoniazid) ➢4. increased concentration of antagonist/competitor (sulfonamide
resistance with increased PABA synthesis). ➢5. altered amount of receptor (trimethoprim-DHFR amplification) ➢6. altered structure of target to reduce binding (methicillin
Inactivation of aminoglycosides by acetylation, phosphorylation, and adenylation in drugresistant organisms
Acquired Drug Resistance
➢1. enzymatic inactivation (b-lactams, aminoglyc. chloramph) ➢2. rapid efflux of drug out of cell (tetracyclines, ciprofloxacin)
➢ phage transduction ➢ transposable elements ➢ plasmid transfer during conjugation
• plasmids can contain multiple resistance genes • transfer can occur between non-pathogen and pathogens