3/16/2016. Marguerite A. Erme, DO, MPH Medical Director Summit County Public Health

Transcription

1 Marguerite A. Erme, DO, MPH Medical Director Summit County Public Health By the end of the presentation, the participant will be able to: Describe the history of antibiotic development and antibiotic resistance List consequences of antibiotic resistance Describe various governmental and health care association strategies to combat antibiotic resistance Outline steps that healthcare organizations and the public can do to decrease antibiotic resistance Infectious diseases have been afflicting humans for millenia. Evidence of smallpox has been found in a 3000 year old Egyptian mummy Hippocrates wrote about the spread of disease by means of air, water, and places, and made an association between climate/diet/living conditions and disease. Epidemics of leprosy, plague, syphilis, smallpox, cholera, yellow fever, typhoid fever, and other infectious diseases were the norm. 1

2 Blood letting Opening a vein Cupping Leeches Chemicals Mercury Arsenic Herbal Quinine Artemesinin Honey While ancient peoples did not understand the etiology of infections, they would use materials that could have inherent antibacterial properties. Greeks and Indians used molds and other plants to treat infections. In Greece and Serbia, moldy bread was traditionally used to treat wounds and infections. Warm soil was used in Russia by peasants to cure infected wounds. The basis of some treatments may not be so easy to understand. Sumerian doctors gave patients beer soup mixed with turtle shells and snake skins. Babylonian doctors healed the eyes using a mixture of frog bile and sour milk. 2

3 Antibiotic: A soluble substance derived by a mold or bacterium that kills or inhibits the growth of other microorganisms. Stedman s Medical Dictionary through Antibiotics can be Natural About 2/3 of natural antibiotics are isolated from terrestrial soil actinomycetes Synthetic Although synthetic antibiotics do not meet the traditional definition of antibiotics, they are used to achieve the same purpose. Semi-synthetic John Parkington recommended using mold for treatment in his book on pharmacology John Tyndall explained antibacterial action of the Penicillium fungus to the Royal Society Sir Alexander Fleming discovered enzyme lysozyme and the antibiotic substance penicillin from the fungus Penicillium notatum Mass produced for the military in Gerhard Domagk discovered Sulfonamidochrysoidine (Prontosil) Selman Waksman used the term "antibiotics" to describe them 1940's and 50's - streptomycin, chloramphenicol, and tetracycline were discovered Timeline of Antibiotic Development 3

4 Timeline of Antibiotic Development "The Race Against Drug Resistance" A Report of the Center for Global Development's Drug Resistance Working Group,

5 Antibiotics work in either of the following two ways: A bactericidal antibiotic kills the bacteria generally by either interfering with the formation of the bacterium's cell wall or its cell contents. Examples: Penicillin, daptomycin, fluoroquinolones, metronidazole, nitrofurantoin and co-trimoxazole A bacteriostatic antibiotic stops bacteria from multiplying by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism. Examples: tetracyclines, sulphonamides, spectinomycin, trimethoprim, chloramphenicol, macrolides and lincosamides. Antibiotic Resistance is the ability of a microorganism to withstand the effects of an antibiotic that was previously effective against it. Antimicrobial resistance involves other microorganisms besides bacteria. The inactivation or modification of the antibiotic An alteration in the bacterial target site of the antibiotic that reduces its binding capacity The modification of bacterial metabolic pathways to dodge the antibiotic effect The reduced intracellular antibiotic accumulation by decreasing permeability and/or increasing active efflux (flowing out) of the antibiotic 5

6 Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. It is an increasingly serious threat to global public health that requires action across all government sectors and society. Antimicrobial resistance is present in all parts of the world. New resistance mechanisms emerge and spread globally. At least 2 million people in the US become infected with antibiotic resistant bacteria each year. At least 23,000 people in the US die each year from antibiotic resistant infections. The cost of excess healthcare costs of resistant infections is estimated to be $20 billion dollars in the US. It is estimated that, by 2050, the global cumulative cost of antibiotic resistance will reach 100 trillion US Dollars (USD) 6

7 Urgent Threats Clostridium difficile Carbapenem-resistant Enterobacteriaceae (CRE) Drug-resistant Neisseria gonorrhoeae Serious Threats Multidrug-resistant Acinetobacter Drug-resistant Campylobacter Fluconazole-resistant Candida (a fungus) Extended spectrum β- lactamase producing Enterobacteriaceae (ESBLs) Vancomycin-resistant Enterococcus (VRE) Serious Threats (continued) Multidrug-resistant Pseudomonas aeruginosa Drug-resistant Nontyphoidal Salmonella Drug-resistant Salmonella Typhi Drug-resistant Shigella Methicillin-resistant Staphylococcus aureus (MRSA) Drug-resistant Streptococcus pneumoniae Drug-resistant tuberculosis Concerning Threats Vancomycin-resistant Staphylococcus aureus (VRSA) Erythromycin-resistant Group A Streptococcus Escherichia coli Resistance to 3rd generation cephalosporins and to fluoroquinolones Klebsiella pneumoniae Resistance to 3rd generation cephalosporins and to carbapenems Staphylococcus aureus Methicillin resistance, or MRSA Streptococcus pneumoniae Resistance (non-susceptibility) to penicillin Non-typhoidal Salmonella (NTS) Resistance to fluoroquinolones Shigella species Resistance to fluoroquinolones Neisseria gonorrhea Reduced susceptibility to 3rd generation cephalosporins Malaria In parts of the Vietnam, resistance to the best available treatment for falciparum malaria, artemisinin-based combination therapies, has been detected. Urinary Tract Infection Resistance to one of the most widely used antibacterial drugs for the oral treatment of urinary tract infections caused by E. coli fluoroquinolones is very widespread. Gonorrhea Treatment failures due to resistance to treatments of last resort for gonorrhea (third-generation cephalosporins) have been reported from 10 countries. Gonorrhea may soon become untreatable as no vaccines or new drugs are in development. Tuberculosis (TB) Globally, 3.5% of new TB cases and 20.5% of previously treated TB cases are estimated to have multi-drug resistant TB (MDR-TB). Extensively drug-resistant TB has been identified in 100 countries, in all regions of the world WHO s 2014 report on global surveillance of antimicrobial resistance 7

8 Bacterial factors Resistance genes transferred among bacteria horizontally and vertically and by bacteriophages Human antibiotic use Food industry antibiotic use There is evidence that resistance elements were present before the introduction of antibiotics. Bacteria have had the ability to develop antibiotic resistance without human input. Resistance genes have been found in bacteria DNA hidden 30,000 years in the permafrost. Antibiotic resistance to antibiotics such as penicillin G and streptomycin were observed within a few years after antibiotic introduction. It appears that evolution of bacterial resistance to antibiotics is a natural process. Human use and misuse of antibiotics has put unnatural pressure which has accelerated the antibiotic resistance development. Poor infection control practices, inadequate sanitary conditions and inappropriate food-handling encourage the further spread of antimicrobial resistance 8

9 According to a recent survey (1100 patients and nearly 800 providers (including physicians, nurse practitioners, and physician assistants) conducted by Medscape (Too Many Antibiotics! Patients and Prescribers Speak Up) The providers (across all specialties) generally confirmed that they regularly prescribe antibiotics when they are not absolutely certain that antibiotics are necessary. When providers were asked why they prescribed antibiotics even when they were not certain the antibiotics were necessary, answers included the following: Prescriptions were written when the providers were "certain enough" that antibiotics were needed (53%); Discomfort with the possibility that an infection could be bacterial (42%); The patient is ill, and the lab work will take too long (31%); The infection did not appear to be viral or fungal (30%); The patient did not want or could not afford a test (19%) Malpractice concerns (15%). Too Many Antibiotics! Patients and Prescribers Speak Up, Medscape, June 27, 2014 So here's the real common thread that cuts across both providers and patients who are confronted by common, mild outpatient infections in the 21st century: Antibiotics are a psychological crutch. Both provider and patient feel better in that if there is a chance that an infection is bacterial, the patient has been adequately cared for with a decreased risk for harm. Too Many Antibiotics! Patients and Prescribers Speak Up, Medscape, June 27, 2014 Reliable data about patterns of use and quantity are not available. Antibiotics used in food animals for three reasons Treat clinical disease Prevent and control common disease events Enhance animal growth Concern is with the non therapeutic uses 9

10 Strong scientific evidence that antibiotic use in food-producing animals can harm public health Use of antibiotics in food-producing animals allows antibiotic-resistant bacteria to thrive while susceptible bacteria are suppressed or die. Resistant bacteria can be transmitted from foodproducing animals to humans through the food supply. Resistant bacteria can cause infections in humans. Infections caused by resistant bacteria can result in adverse health consequences for humans. 10

11 Released March 2015 Developed by the interagency task force in response to Executive Order 13676: Combating Antibiotic-Resistant Bacteria, outlines steps for implementing the National Strategy on Combating Antibiotic-Resistant Bacteria Addresses the policy recommendations of the President s Council of Advisors on Science and Technology (PCAST) report on Combating Antibiotic Resistance. Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections. Strengthen National One-Health Surveillance Efforts to Combat Resistance, Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria. Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines. Improve International Collaboration and Capacities for Antibiotic Resistance Prevention, Surveillance, Control, and Antibiotic Research and Development. There are four core actions to help fight these antibiotic resistant infections: Preventing infections and preventing the spread of resistance Tracking resistant bacteria Improving the use of today s antibiotics Promoting the development of new antibiotics and developing new diagnostic tests for resistant bacteria 11

12 Prevent Infections Clean hands Vaccines Prevent food-borne infections Keep water safe Prevent STDs Protect self while hospitalized Decrease Resistance Use antibiotics the correct way Don t insist on antibiotics for viral infections Use symptomatic relief CDC Protecting Yourself and Your Family - cting_yourself_family.html 2016 Get Smart Week is November Get Smart About Antibiotics Week is an annual oneweek observance to raise awareness of the threat of antibiotic resistance and the importance of appropriate antibiotic prescribing and use. 12

13 The Food and Drug Administration (FDA) is implementing a voluntary plan with industry to phase out the use of certain antibiotics for enhanced food production. FDA is working to address the use of medically important antibiotics in foodproducing animals for production uses, such as to enhance growth or improve feed efficiency. EIP ABC HAIC FoodNet NARMS NHSN GISP NTSS 13

14 Active Bacterial Core surveillance (ABCs): Tracking infections caused by Neisseria meningitidis, Streptococcus pneumoniae, Groups A and B Streptococcus, and methicillin-resistant Staphylococcus aureus Gonococcal Isolate Surveillance Project (GISP): Collecting isolates from gonorrhea infections to monitor antibiotic resistance National Tuberculosis Surveillance System (NTSS): National Electronic Disease Surveillance System (NEDSS)-based reporting of tuberculosis cases including resistance data Healthcare-Associated Infections-Community Interface (HAIC): Tracking infections with C. difficile and with multidrug-resistant gram-negative microorganisms. Established in 1996 as a collaboration among CDC, FDA, USDA, and state and local public health departments Primary objectives Monitor trends in antibiotic resistance among enteric bacteria from humans, retail meats, and food-producing animals. Disseminate information on antibiotic resistance to promote interventions that reduce antibiotic resistance among foodborne bacteria. Conduct research to better understand the emergence, persistence, and spread of antibiotic resistance. Provide data that assist the FDA in making decisions about approving safe and effective antibiotic drugs for animals. NARMS is the only source of national information on antibiotic resistance in foodborne pathogens. Good News Multidrug resistance in Salmonella was similar to previous year and has remained stable over the past ten years 2013: 10%; : 11% Bad News Salmonella typhi resistance to a quinolone drug was higher in 2013 (67%) than in the baseline period of (53%) Multi-drug resistance in a common Salmonella serotype (l 4,[5],12:i:-) continues to rise Resistance more than doubled since 2011 (18% in 2011 vs. 46% in 2013) Has been linked to animal exposure and consumption of pork or beef, including meats purchased from live animal markets 14

15 Antibiotic stewardship is the development, promotion, and implementation of activities to ensure the appropriate use of antibiotics. Undertaken by healthcare organizations Created an Antibacterial Stewardship Policy Statement in 2012 with following recommendations: Antimicrobial stewardship programs should be required through regulatory mechanisms Antimicrobial stewardship should be monitored in ambulatory care settings Education about antimicrobial resistance and stewardship must be accomplished Antimicrobial use data should be collected and readily available for both inpatient and outpatient settings. Research on antimicrobial stewardship is needed. 15

16 Leadership Commitment Dedicating necessary human, financial and information technology resources Accountability Appointing a single leader responsible for program outcomes. Appointing a single pharmacist leader responsible for working to improve antibiotic use. Action Implementing at least one recommended action, such as systemic evaluation of ongoing treatment need after a set period of initial treatment (i.e. antibiotic time out after 48 hours) Tracking Monitoring antibiotic prescribing and resistance patterns Reporting Regular reporting information on antibiotic use and resistance to doctors, nurses and relevant staff Education Educating clinicians about resistance and optimal prescribing After the IDSA guidelines came out there was a decline in both all and select antibiotic use in hospitals with and without antimicrobial stewardship programs. Hospitals that had formalized antimicrobial stewardship programs had a more pronounced decline in overall antibiotic use than hospitals without antimicrobial stewardship program Antimicrobial Stewardship Programs in Freestanding Children s Hospitals, Hersh Al, et al, Pediatrics, content/early/2014/12/02/peds

17 Number of new agents decreased steadily over last few decades More success with development of new compounds in already known antibiotic classes Lack of diversity in bacterial cellular targets More antibiotics for gram positive bacteria than gram negative bacteria Development of synthetic antibiotics extremely rare Biggest issue with synthetic antibiotic development is the issue of bacterial cell penetration 29 antibiotics approved in US in the 1980s 23 antibiotics approved in US in the 1990s 9 antibiotics approved in US between 2000 and 2010 As of September 2014, there were 38 experimental antibiotics in clinical testing Only 2 novel classes of antibiotics have reached the US market since % of all drugs that enter clinical development fail for lack of efficacy or toxicity Scientific The easiest antibiotics to develop have already been discovered. Economic Development Cost On average, pharmaceutical companies spend $5 billion in research and testing for each new drug they bring to market. Because about 80 percent of the drugs emerging from labs fail in safety or efficacy testing, pharmaceutical companies need to recoup billions from each drug that comes to market. Profits Greater profits on drugs that can be used regularly without losing effectiveness, such as antidepressants, statins, and antiinflammatory medications. Regulatory Antibiotic approval by FDA confusing, long, convoluted 17

18 2012-Congress passed the GAIN Act (Generating Antibiotics Incentives Now) Purpose to lessen economic hurdles to antibiotic development by promising a better return on investment for critically needed drugs Antibiotics may receive fast tract and priority review status from FDA Approved antibiotics receive an additional 5 years of exclusivity from competition with generics Twenty-nine companies working on antibiotic development Only 4 are in the top fifty pharmaceutical companies People can help tackle resistance by: Hand washing, and avoiding close contact with sick people to prevent transmission of bacterial infections and viral infections such as influenza or rotavirus, and using condoms to prevent the transmission of sexuallytransmitted infections; Getting vaccinated, and keeping vaccinations up to date; Using antimicrobial drugs only when they are prescribed by a certified health professional; Completing the full treatment course (which in the case of antiviral drugs may require life-long treatment), even if they feel better; Never sharing antimicrobial drugs with others or using leftover prescriptions 18

19 Health workers and pharmacists can help tackle resistance by: Enhancing infection prevention and control in hospitals and clinics; Only prescribing and dispensing antibiotics when they are truly needed; Prescribing and dispensing the right antimicrobial drugs to treat the illness Policymakers can help tackle resistance by: Improving monitoring around the extent and causes of resistance; Strengthening infection control and prevention; regulating and promoting appropriate use of medicines; Making information widely available on the impact of antimicrobial resistance and how the public and health professionals can play their part; Rewarding innovation and development of new treatment options and other tools. Policymakers, scientists and industry can help tackle resistance by: Fostering innovation and research and development of new vaccines, diagnostics, infection treatment options and other tools Use antibiotics only to treat infections in food animals Use antibiotics that are not typically used in humans 19

20 Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013 Public Health Reports, A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential, January February 2012 / Volume 127 Centers for Disease Control and Prevention, Achievements in Public Health, : Control of Infectious Diseases Thank you 20