抗生素的将来（英文PPT）Whatfuture for .pptVIP

BPC 2006: Innovation in antibiotic drug discovery What future for antibiotics? Anthony W. Smith, BPharm, PhD, MRPharmS Dean The pre-antimicrobial era Black death in 14th and 15th centuries European population halved Puerperal (streptococcal) sepsis Accounted for 70% of deaths in birthing mothers Typhus Napolean Bonaparte’s army reduced from 665,000 to 93,000. Returners infected and killed 2,000,000 Influenza 1918 – 19 pandemic killed 30,000,000 in Europe, Asia, Australia and the Americas TB One of the biggest killers of mankind – 1,750,000 killed in 2003 Milestones in antimicrobial chemotherapy 1929 Fleming discovers penicillin 1935 Gerhard Domagk develops sulphonamides 1939 Discovery and purification of gramicidin by René Dubos 1941 USA commences commercial production of penicillin 1945 The “golden age of antibiotics” begins with the introduction of cephalosporins, chloramphenicol, tetracyclines, erythromycin, vancomycin, gentamicin and many variations on the penicillin (b-lactam) nucleus Milestones in antimicrobial chemotherapy 1953 Multi-drug-resistant dysentery bacilli in Japan. Drug-resistant TB 1960 Methicillin-resistant S. aureus 1980s Major drug companies scale-down antibiotic discovery programmes 2000 Linezolid launched – first new class of agents in 30 years World Health GLOBAL INFECTIOUS DISEASE STATISTICS (Sep 04) b-Lactams - mode of action Emergence of antibiotic resistance by selective pressure EDG Murray (1917 – 1954) strain collection ‘pre-antibiotic era’ isolates of enteric bacteria practically fully sensitive to a range of antibiotics 2/433 penicillin resistant 9/433 tetracycline resistant Rapid emergence of resistance of the past 60 years Mutation Genetic re-arrangement Genetic resistance determinants Resistance genes can be spread by horizontal transfer Hospital-acquired infections to drug-resistant bacteria (USA 2002) MRSA in Europe (2002 data) Greece 48.6% UK 44.5% Germany 27.2% Spain 23.5% Belgium 19.2% Czech Republic 6.2% Net