抗生素耐药 Resistance to antibiotics课件.ppt

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 e.g. sulfonamide resistance if high purines, methionine, thymidine available (such as in an abscess) e.g. aminoglycosides not effective in anaerobic environment Acquired Resistance genetic changes, plasmids with new genes 2006 Antibiogram Harborview/UW Drug export systems in Gram + Vancomycin resistance: mechanism 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 Problems with Antibiotic resistance more than 50% of antibiotics used in domestic animals for sub-therapeutic effect: breeding ground for resistance Antibiotics given to pigs as of 2000 “KFC does not purchase poultry treated nontherapeutically with medically important antibiotics.” – Letter to “Keep Antibiotics Working,” August 28, 2002 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 Prospects for new antibiotics? new antibiotic development slowed in 80’s/90’s selective drugs have lower market value 5-15 yr time frame to get new drugs to physicians recent increase in new antibiotic development is encouraging Plasmid Mediated Quinolone Resistance (PMQR) First reported in a strain of K. pneumoniae QnrA protein – 218 aa protein Protects DNA gyrase and top