Multi-Drug Resistant Superbugs- What s the Big Deal? Toni Biasi, RN MSN MPH CIC Infection Prevention Indiana University Health Imagine A World Without Antibiotics A World Where Simple Infections can be Life Threatening That World is Fast Approaching Antibiotic Resistance is already occurring 1915 - PRE-ANTIBIOTIC ERA One hundred years ago, there were no antibiotics. Infections were treated with folk remedies and tender loving care, if treated at all. And it s happening right now across the world Many people died from injuries that caused infections Infections that today are easily treatable.
The Age of Antibiotics The miracle drugs! Cures almost everything! Take antibiotics, just to be safe! The Age of Antibiotics 80% of all antibiotics go to farm animals & used in certain crops The Age of Antibiotics Year Antibiotic Years to Resistance 1943 Penicillin 2 1972 Vancomycin 16 1995 Imipenem 2 2003 Daptomycin 2 Organisms become resistant to Antibiotics within an average of 8 years.. 10 Source: Antimicrobial Resistance Global Report WHO 2014 and CDC.gov 8/25/2015 2013 CDC 2013 CDC Prioritized 18 organisms Antibiotic Resistance Threats Superbug CRE according to public health threat Carbapenem-resistant Risk to become widespread Enterobacteriaceae Drug-Resistant gonorrhea Clostridiuim difficile (Cdiff) (Expected to Worsen) (Causes Severe Illness) ESBL s VRE MRSA Vancomycin-resistant Staph aureus Erythromycin-resistant Strep A Clindamycin-resistant Strep B
Why is this Happening? Why are germs becoming resistant? Bacteria have learned how to OUTSMART antibiotics designed to kill them Understanding The first life forms on earth They re Everywhere! Cover Everything! Human Body 10X more bacterial cells than human cells Most are harmless Many are beneficial! It s ALL about Survival! They fight to stay relevant, stay alive, and to produce another generation They adapt to their environment
Survival By Infecting as many other s as possible! Create conditions to irritate or harm it s host! Examples: MRSA = Draining sores Cdiff = Diarrhea Rhinovirus = Coughing, Sneezing We know these as symptoms, but the microbes see it as transportation to infect the next host & continue to replicate! One-way ticket OUT! Let s Talk HANDS! Once out of the body, people s HANDS become germ transportation HANDS are a vehicle that germs have learned to use to spread themselves to the next host. How Do Bacteria Become Resistant in the First Place? 3 Ways.. How Do Bacteria Become Resistant? 1. Mutation How Do Germs Become Resistant? 2. They Share! Share pieces of their antibiotic-resistant genes!
3 Ways bacteria SHARE genes (to make other bacteria antibiotic resistant) Bacteria SHARE genes 1. Cannabalism (Transformation).. Bacteria eat dead bacteria, & acquire its genetic material. The hungry bacteria now exhibit the traits of the genes they just picked up. Bacteria SHARE genes 2. Viral Pass (Transduction) Virus transfers genes from bacteria to bacteria Bacteria SHARE genes 3. You Sexy Thaaang (Conjugation) Bacterial sex transfers genetic info The sharing of genes are what ISOLATION precautions tries to STOP! Resistance Mechanisms How Do Bacteria actually RESIST Antibiotics?
How do bacteria resist? 1. Barfing Bacteria.. The antibiotic gets in, but is ejected back OUT (via efflux pumps) How do bacteria resist? 2. The Chameleon Bacteria change the cell membrane Antibiotic cannot enter the cell Essentially makes the bacteria invisible to the antibiotic How do bacteria resist? The Sniper Bacteria produce enzymes, go on the ASSAULT to disable the antibiotic Superbugs the basics.. Gut Bugs Antibiotic Classes Enzymes Superbugs Bacteria that can t be killed, even with standard antibiotics Superbugs Originate (mostly) in Bacteria of the Gut Called gram-negative Enterobacteriaceae (CRE = Carbapenem resistant Enterobacteriaceae) Live in the Intestines Most bacteria are harmless, some even helpful
Common Enterobacteriaceae E coli Klebsiella pneumoniae Enterobacter cloacae Serratia marcescens Major Antibiotic Classes Sulfonamides Quinolones Tetracyclines - Macrolides Aminoglycosides Beta Lactams PENICILLINS CEPHALOSPORINS CARBAPENEMS Proteus mirabilis Beta-Lactam Antibiotics Beta-Lactams Antibiotics - Contains a Lactam Ring.. Beta-lactam antibiotics: Penicillins Cephalosporins Carbapenems Lactam Ring Enzymes Microbiology world word ending in ase = enzyme Enzymes coded to break down certain things Superbug Enzymes.. Lactamases = break down lactam rings.. Carbapenemases = breaks down carbapenem lactam rings Superbugs Putting it all together ESBL- Extended-Spectrum Beta Lactamase Not-Quite a Superbug..Yet
ESBL- Extended-Spectrum Beta Lactamase MDR Gut Bugs Produce Lactamases Respiratory Culture Escherichia Coli Extended Spectrum Beta-Lactamase Producer Note: Still susceptible to the Carbapenem E. Coli Klebsiella pneumoniae Proteus Mirabilis Penicillins Cephalosporin's Cephalosporins Penicillin ESBL Culture report History of ESBL s Uncommon in the U.S. before 1992 Multi-drug resistant (MDR) AND ESBL Producer Increasing incidence especially in past 10 years What s the Big Deal? 57% Patients with ESBL in the blood Are more likely to die vs those with a non-esbl producing strain Superbug CRE Carbapenem Resistant Enterobacteriaceae
CRE- Carbapenem-Resistant Enterobacteriaceae Overview MDR Gut Bugs Produce Carbapenemases Urine Culture Klebsiella pneumoniae Positive for Carbapenemase Production E. Coli Klebsiella pneumoniae Penicillins -Oxacillin -Ampicillin Cephalosporins -Ceftriaxone -Ceftazidime (all 3 rd gen tested) Carbapenem Resistant Proteus Mirabilis Carbapenems -Meropenem -Imipenem (at least 1) What s the big deal? Carbapenems are the antibiotics of LAST RESORT for these gut bugs CRE Increasingly Resistant Over past 10 yrs, CRE has increased by 400% in the United States Why so scary? Kills up to HALF of patients who get bloodstream infections from CRE CRE & ESBL Risk ICU patients. Enter through invasive devices tube feeding sites, urinary catheters, central lines,etc... Loves immuncompromised patients! Patients taking antibiotics, esp. Carbapenems or Cephalosporins Long term care facility up to 75% Healthcare Worker Risk Very low risk Use standard precautions always! Use contact isolation precautions if CRE is known! The Path of Least Resistance!
Prevalence of CRE in 2006 Prevalence of CRE in 2015 Prevalence of CRE (as of Feb 2015) Preventing Transmission in a healthcare setting Use Contact Precautions Recent Publications 2014 World Health Organization Isolate for active infection AND history of (colonization issues) To protect ourselves AND other patients to not spread it outside the room no guidelines for d/c isolation at this time The Problem - A Global Threat Severe Antibiotic Resistance It s happening RIGHT NOW across the world. No system for global antibiotic tracking Modern medicine will be obsolete and minor injuries will once again be deadly, if no urgent action now 60 { 8/25/2015 Source: Antimicrobial Resistance Global Report WHO 2014
WHO: Other Evolving Anti-Drug Resistance Global Antibiotics Prescriptions Data from 114 Countries High levels of resistance in all parts of the world Anti-fungal drugs becoming less effective Salmonella Fluoroquinolone resistant Shigella Fluoroquinolone resistant Until recently, only 2% resistant Recent outbreak = 90% MDR Neisseria gonorrhea Much resistance to standard abx treatments Source: www.cdc.gov CDC: One-third to one-half of all antibiotics used in inpatient and outpatient settings are either unnecessary or incorrectly prescribed. New Antibiotics Developed.. Pharma Economics Antibiotic Resistance will kill more people per year than cancer by 2050 $$ for R & D Limited lifespan/earning capacity of abx Stockholder s interests Develop meds for chronic or lifestyle conditions Source: UK Review on Antibiotic Resistance (2014) (AMR = Anti Microbial Resistance)
Think about if no antibiotics.. What Are We Doing as a Nation? What Would That Mean To You? Life as we know it would change National Action Plan.. Presidential Executive Order - Signed Sept 2013 Plan Announced March 2015 Multi-agency task force 5 Goals Completion by 2020 Goal #1 Slow The Emergence of Resistant Bacteria Reduce inappropriate abx use Increase public reporting of antibiotic use Tie abx use to hospital payments Reduce antibiotic use in livestock 69 8/25/2015 Goal #2 Strengthen National One-Health Surveillance Create a mechanism for central reporting of: Abx Resistance Abx Sales & Usage Animal/Ag Use Goal #3 Develop Rapid & Innovative Diagnostic Tests for Resistant Bacteria Develop point-of-care tests that rapidly: Distinguish between bacterial vs viral infections Determine antibiotic resistant profiles Avoiding the broad spectrum abx use Many agencies operating in silo s, no central data keeper
Goal #4 R & D $$ for New Antibiotics, Other Therapeutics, and Vaccines Problem: Lack of new antibiotic developments Support development of declined over the years. -Advancement of at least 2 new abx drug candidates -Develop antibiotic alternative treatments -Develop vaccines to prevent infection of antibiotic resistant organisms Goal #5 International Collaboration for Antibiotic Resistance Prevention, Surveillance, Control, and R & D Problem: Antibiotic resistance is a global problem. Make antibiotic resistance an international priority Establish a U.S.- European Union for sharing/analyzing bacterial resistance patterns Develop a global antibiotic resistance database In Conclusion It s not the strongest of the species that survives, nor the most intelligent. It is the one that is most adaptable to change. References www.cdc.gov www.who.int Charles Darwin