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)
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
➢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
➢ “KFC does not purchase poultry treated nontherapeutically with medically important antibiotics.” – Letter to “Keep Antibiotics Working,” August 28, 2002
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)
• e.g. sulfonamide resistance if high purines, methionine, thymidine available (such as in an abscess)
• e.g. aminoglycosides not effective in anaerobic environment
resistance, vancomycin resistance, ciprofloxacin res.)
Vancomycin resistance: meபைடு நூலகம்hanism
Vancomycin resistance: mechanism
Resistance can be transferred between bacteria
➢ phage transduction ➢ transposable elements ➢ plasmid transfer during conjugation
• plasmids can contain multiple resistance genes • transfer can occur between non-pathogen and pathogens
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
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
➢ 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
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