抗生素的过去、现在与将来（英文ppt）课件

Medicine. Past, Present and Future. ANTIBIOTICS,Professor Anthony Coates Medical Microbiology Department of Cellular and Molecular Medicine, St Georges, University of London.,Microbes kill each other with antibiotics,They have developed self-defence mechanisms: 1. Non-multiplying state 2. Biofilm 3. Genetic resistance,The search for antibiotics begins,Bacterial genetic resistance to antibiotics begins to neutralise the beneficial effects.,1945, in an interview with The New York Times, Fleming warned that the misuse of penicillin could lead to selection of resistant forms of bacteria The solution: Make new antibiotics to replace the old ones to which resistance has emerged.,Antibiotic development 1929-72,The Antibiotic Paradox, Stuart Levy, New York, Plenum Press, 1992, 4,THE PRESENT,Antibiotic resistance is rising,80,70,60,50,40,30,20,10,0,1990,1995,2000,2003,Percent,of,Resistant,Strain,MRSA,QRPSE,MRSPN/VRE,PRSPN,MRSA = methicillin resistant Staphylococcus aureus VRE = vancomycin resistant enterococci MRSPN = macrolide resistant Streptococcus pneumoniae PRSPN = penicillin resistant Streptococcus pneumoniae QRPSE = quinolone resistant Pseudomonas aeruginosa,The number of new antibiotics which reach the market is falling,Life-or-death Crisis: The Bacteria are winning,Emergence of resistance is outpacing the introduction of new antibiotics (2003 Daptomycin; 2004 none; 2005 Tygacil ) No new agents in clinical development against multi-drug resistant gram-negatives eg Pseudomonas aeruginosa, Acinetobacter spp,Why has the pharmaceutical industry reduced its production of new antibiotics?,Resistance emerges too quickly and reduces the effective life of an antibiotic Too little profit Big Biology has failed to produce new antibiotics Increased costs due to more regulation eg EC Litigation fears Government restrictions on use (Keep in reserve),Antibiotic use in todays world,Amoxil and Augmentin 25% of all presciptions More than $1 billion sales per year for Augmentin, Klacid, Zithromax and Levaquin. (IMS Health, IMS Midas, /globalinsights),THE FUTURE,International response to the global spread of antimicrobial resistance,Improve standards of antimicrobial prescribing and so prolong the life of existing antimicrobials Vaccines Prevention by improved infection control Limited impact so far,Production of new antibiotics,GlaxoSmithKline has two in development Johnson and Johnson active Pfizer active Novartis have entered antibiotic R&D (Personal Communication, Halls GA, medical marketing services, ),ROW = rest of world; CAP = community-acquired pneumonia; cSSTI = complicated skin and skin structure infections; VAP = ventilator-associated pneumonia Ref: Personal Communication Halls GA, medical marketing services, 34 Ledborough Lane, Beaconsfield, Bucks HP9 2DD, UK; ,Methods of generation of new antibiotics,A new approach: develop antibiotics which kill non-multiplying bacteria Survive very high concentrations of antibiotics Source of continuing infection May be responsible for emergence of genetic resistance,Antibiotic,Die,Multiplying,Non-Multiplying,Survive,Multiplying,Clinical Disease,0,1,2,3,4,5,6,7,8,9,0,5,10,15,20,25,30,35,40,45,50,Concentrations of Drugs (ug/ml),Log CFU/ml,Augmentin,Levofloxacin,Azithromycin,Linezolid,HT31,HT42,Staphylococcus aureus stationary phase,0,1,2,3,4,5,6,7,8,0,10,20,30,40,50,60,70,80,Concentrations of Drugs (ug/ml),Log CFU/ml,Vancomycin,HT31,HT42,Methicillin resistant S. aureus stationary phase,New antimicrobial agents which kill non-multiplying bacteria,Potential Use in combination with anti-multiplying compounds Will shorten the duration of chemotherapy May reduce the emergence of resistance,Conclusions,Past Antibiotics have revolutionised medicine and have saved millions of lives Present Increasing bacterial resistance and falling antibiotic production is reducing the efficacy of antibiotics Future A continuous supply of new antibiotics is needed, with activity against non-multiplying bacteria,Acknowledgements,Yanmin Hu Clive Page*