The USis notimmune: 2 million people -acquire bacterialinfection in USResistantStrainsSpreadRapidlyhospitals/year.605090,000 people -dieR480→MRSAof this infection-VRE-FQRP70% of these0infections from100bacteria resistant to19801985199019952000at least one drugSource:CentersforDiseaseControlandPrevention $ 5 billion - annualMRSA=Methicillin-resistantStaphylococcusAureusVRE=Vancomycin-resistantantEnterococcicost of"resistance”FQRP=Floroquinolone-resistantPseudomonasaeruginosa(moreexpensivedrugs, longerhospital stay)
• 2 million people - acquire bacterial infection in US hospitals/year. • 90,000 people - die of this infection • 70% of these infections from bacteria resistant to at least one drug • $ 5 billion - annual cost of “resistance” (more expensive drugs, longer hospital stay) The US is not immune
Thetypicalstoryofresistance1940sPenicillinkeptStaphylococcusbacteriaundercontrol1942Penicillin-resistant Staphbacteria were identifiedlate 1960s >80percent of Staphbacteria were penicillin-resistant.1961Methicillin was introduced to combat resistant Staphbacteria.19742percentofthe Staphbacteriafound inU.S.hospitalsmethicillin-resistant2002Jumpto57.1percentStaphbacterianowresistant.1958Vancomycin was introduced to combatresistantStaphbacteria.late1990sStaph bacteria partially resistant to vancomycin2002Two cases of fully vancomycin-resistant Staph (VRSA)2002Recognitionofcommunity-acquired Staph infections.70%ofchildrenattheUniversityofTexas infected withMRSA
• 1940s Penicillin kept Staphylococcus bacteria under control. • 1942 Penicillin-resistant Staph bacteria were identified • late 1960s > 80 percent of Staph bacteria were penicillin-resistant. • 1961 Methicillin was introduced to combat resistant Staph bacteria. • 1974 2 percent of the Staph bacteria found in U.S. hospitals methicillin-resistant. • 2002 Jump to 57.1 percent Staph bacteria now resistant. • 1958 Vancomycin was introduced to combat resistant Staph bacteria. • late 1990s Staph bacteria partially resistant to vancomycin. • 2002 Two cases of fully vancomycin-resistant Staph (VRSA). • 2002 Recognition of community-acquired Staph infections. 70% of children at the University of Texas infected with MRSA. The typical story of resistance
Can we always count on the next antibiotic?“"Infectious diseases physicians are alarmed by theprospect that effective antibiotics may not beavailable to treat seriously ill patients in the nearfuture. There simply aren't enough new drugs inthe pharmaceutical pipeline to keep pace withdrug- resistant bacterial infections, so-called“superbugs."JosephR.Dalovisio,MDIDSAPresident
“Infectious diseases physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future. There simply aren’t enough new drugs in the pharmaceutical pipeline to keep pace with drug- resistant bacterial infections, so-called ‘superbugs.’” Joseph R. Dalovisio, MD IDSA President Can we always count on the next antibiotic?
Canwealways count on the next antibiotic? NO!Only2new antibioticswithnewmechanismofaction,nocrossTotalApprovedAntibacterials:USresistancein40years!1998-2008only10new1614antibiotics FDA12approved108■Total#NewIn 2002, among 896AntibacterialAgentsmedicines emerging on42market.nonewasanantibiotic1983-1988-1993-1998-200319871992199720022007In2004,of506drugsinSpellberg,etal.,CIDMay12004,Modifieddevelopmentpipelineonly 5 are antibiotics (vs.67 in cancer)
• Only 2 new antibiotics with new mechanism of action, no cross resistance in 40 years! • 1998-2008 only 10 new antibiotics FDA approved • In 2002, among 89 medicines emerging on market, none was an antibiotic • In 2004, of 506 drugs in development pipeline, only 5 are antibiotics (vs. 67 in cancer) Can we always count on the next antibiotic? NO!
Challengesunigueto antibioticdiscovery&development:Shortcourses:Limited utility when resistance develops(bacteria evolved much more rapidly)Technically difficult to find. Goal broad spectrum antibioticsLimited willingness of specialiststo use newdrugs. Median time for clinical testing and FDA approval 6 years(additional ~ 8 prior to clinical testing)Only 1/5000 in clinical testing make it to FDA approval
• Short courses • Limited utility when resistance develops (bacteria evolved much more rapidly) • Technically difficult to find • Goal broad spectrum antibiotics • Limited willingness of specialists to use new drugs • Median time for clinical testing and FDA approval 6 years (additional ~ 8 prior to clinical testing) • Only 1/5000 in clinical testing make it to FDA approval Challenges unique to antibiotic discovery&development