Misuse of Antibiotics: The Worldwide Crisis of Resistant Bacterial Infections,James A. Wilde MD Medical Director, GUARD Associate Professor of Emergency Medicine and Pediatrics Medical College of Georgia,What Causes Infections?,Infections are caused by one of four life forms: Virus 75% or more of all infections Bacteria less than 25% Parasites less than 1% in the US Fungus less than 1% in the US,Virus: Can live in the environment for years Attack humans by invading cells of certain organs Hepatitis virus: attacks the liver cells Encephalitis virus: attacks the brain cells Cold virus: attacks the throat and breathing passages Diarrhea virus: attacks the small intestine Cannot reproduce or grow unless inside a cell “Sucks” the energy from the cell, eventually kills it Too small to be seen with most microscopes,Bacteria Easily visible with a microscope Can live and grow wherever they find food Mountain streams Ocean water Rotting animal or plant Sewer Topsoil Blood/skin/throat/lungs/urinary bladder/intestine Some divide and grow every 20 minutes Many produce poisons,Diseases Caused by Viruses and Bacteria,Virus Common cold Diarrhea (99%) Acute Bronchitis Influenza (flu) Measles Chicken Pox AIDS Rabies Hepatitis,Bacteria Urine infections Strep Throat Boils/abscesses Gangrene Some pneumonia Ear infections (half) Sinus infections ( half) Bubonic Plague Tuberculosis,How Do We Cure These Infections?,Bacterial infections Immune system (white blood cells, etc) Antibiotics (Penicillin, etc.) Viruses Immune system Anti-viral medications: not much help Antibiotics do NOTHING to harm a virus,Fact Bacteria are the cause of the vast majority of deaths due to infection in the United States: sepsis, meningitis, pneumonia,Fact Most viral infections get better all by themselves in 1-3 weeks; no medications are required: colds, flu, stomach virus,Resolution of Acute Bronchitis,Stott, BMJ 1976,Gonzales et al., JAMA, 1997,Examined rate of antibiotic use for common cold, bronchitis in private physicians offices Colds: 51% given antibiotics Upper respiratory infection: 52% Bronchitis: 66% These antibiotics are unnecessary!,So Why Do Doctors Give Antibiotics For Viral Infections?,They think you want an antibiotic Its easier than explaining why you dont need one Patients have been “trained” to expect them Doctors think the antibiotics will prevent a secondary bacterial infection (theyre wrong) They misdiagnose a viral infection for a bacterial infection: Sinusitis vs Cold,Problems With Improper Use of Antibiotics,They dont help the patient at all Expense: 75% of outpatient antibiotics are used for respiratory infections Patient expectations: why no better? Side effects: diarrhea, rash, allergy Development of resistance: the antibiotic wont work when you really DO need it for a bacterial infection,HISTORICAL PERSPECTIVE,Antibiotics introduced 60 years ago Bacteria from pre-antibiotic era had virtually no resistance genes Staph aureus was uniformly sensitive to Penicillin at the time of its release,Emergence of Antimicrobial Resistance,Susceptible Bacteria,Mechanisms of Resistance,Enzymatic degradation,Decreased entry,Efflux pump,Altered target site,Bypass pathway,To date, more than 100 resistance genes have been identified These genes allow the bacteria to shield themselves from the antibiotic Resistance genes can be transferred from one bacterial species to another: spread of resistance is RAPID,Chronology of Development of Antibiotic Resistance,Antibiotic Year introduced Resistance identified Penicillin 1942 1940 Streptomycin 1947 1947 Tetracycline 1952 1956 Erythromycin 1955 1956 Gentamicin 1967 1970 Vancomycin 1956 1987,Individual Abx Use & Individuals Risk of Resistant -UTI,Metlay et al. J Antimicrob Chemo 2003,Relationship between Personal and Community Antimicrobial Use and Carriage of Resistant Pneumococci, Alaska,(Hennessy T. ISPPD 2002),Clinical Significance of Antibiotic Resistance,Therapeutic failures and relapse Facilitates spread in the hospital under “antibiotic pressure” Need to use more costly and toxic agents The emergence of untreatable pathogens,S. aureus,Penicillin,1950s,Penicillin-resistant,S. aureus,Evolution of Drug Resistance in S. aureus,Proportion of S. aureus Nosocomial Infections Resistant to Oxacillin (MRSA) Among Intensive Care Unit Patients, 1989-2003*,*Source: NNIS System, data for 2003 are incomplete,Emergence of Vancomycin Resistant Enterococci,Source: NNIS Data,Non-Intensive Care Unit Patients Intensive Care Unit Patients,Development of of Resistance in Gram Positive Pathogens,1Smith TL et al. N Engl J Med. 1999;340:493-501. 2Martone WJ. Infect Control Hosp Epidemiol. 1998;19:539-545. 3Hiramatsu K et al. J Antimicrob Chemother. 1997;40:135-136. 4CDC. MMWR Morb Mortal Wkly Rep. 2002;51:565-567.,Antibiotics in Animal Feed rationale,Promotes growth Decreases amount of feed needed Prevents infectious diseases Facilitates confinement housing Lowers costs,48% of all antibiotics by weight is added to animal feeds to promote growth. Results in low, subtherapeutic levels which are thought to promote resistance. Farm families who own chickens feed tetracycline have an increased incidence of tetracycline resistant fecal flora Chickens at Spanish supermarkets have 90% of cultured campylobacter resistant to quinolones 39% of enterococci in the fecal flora of pigs from the Netherlands is resistant to vancomycin vs 0% in Sweden. (Sweden bans antibiotic additives in animal feed),ANTIMICROBIAL RESISTANCE: The role of animal feed antibiotic additives,Cross-resistance Between Growth Promoters and Antibiotics for Human Use,Avoparcin Vancomycin Avilamycin Everninomicin Virginiamycin Synercid Tylosin Erythromycin,EID 1999; Vol 5,Decrease in VRE After Removing Avoparcin From Animal Feed,US New Antibacterial Agents,Waiting Room Poster,“The ravaging epidemic of AIDS has shocked the worldWe will face similar catastrophes againWe have too many illusions that we cangovern the remaining vital kingdoms, the microbes, that remain our competitors of last resort for dominion of the planet”,1988, Dr. Joshua Lederberg, Nobel Laureate,“The development of new antibiotics without having mechanisms to insure their appropriate use is much like supplying your alcoholic patients with a finer brandy.”,- Dennis Maki, 1998,- From “Managing the Minefield” Satellite Symposium Annual Meeting of the Infectious Diseases Society of America,National Effort to Curb Unwarranted Antibiotics,Surveillance Prevention and Control Research Product Development,Agency for Health Care Research and Quality,Department of Defense,Environmental Protection Agency,Health Care Financing Administration,Health Resources and Services Administration,Department of Agriculture,Department of Veterans Affairs,GUARD: Georgia