Antimicrobial Stewardship Protecting a Valuable Resource November 8, 2011 Medical Director Communicable Disease Service NJDHSS Edward.Lifshitz@doh.state.nj.us (609) 826-5964 One can think of the middle of the twentieth century as the end of one of the most important social revolutions in history, the virtual elimination of infectious diseases as a significant factor in social life 1962 Sir Frank MacFarlane Burnet Director of the Walter and Eliza Hall Institute of Medical Research 1960 Nobel Prize co-winner in Physiology or Medicine Unless we act to protect these medical miracles, we could be heading for a post-antibiotic age 2001 Gro Harlem Brundtland WHO Director-General 1
Antimicrobial Stewardship Antimicrobial stewardship programs in hospitals seek to optimize antimicrobial prescribing in order to improve individual patient care as well as reduce hospital costs and slow the spread of antimicrobial resistance. Clinical Microbiology Reviews, October 2005, p. 638-656, Vol. 18, No. 4 Microbes vs Humans Microbes Humans Microbes by factor # on Earth 5 x 10 31 7 x 10 9 ~ 10 22 # cells in a Human 5 x 10 13 5 x 10 12 ~ 5-10 Mass - kg 5 x 10 19 3 x 10 11 ~ 10 8 Generation time 30 min 30 years ~ 5 x 10 5 Time on earth, years 3.5 x 10 9 4 x 10 6 ~ 10 3 Data: Schaechter M, et al, Microbiology in the 21 st century: Where Are We and Where Are We Going? Chart: Spellberg B, et al, The Epidemic of Antibiotic-Resistant Infections: A Call to Action for the Medical Community from the Infectious Diseases Society of America Ancient times Honey, lard, lint A Brief History ~ 1550 BC Egyptians Moldy bread ~ 2000 years ago many cultures 2
The Magic Bullet 1910 Paul Ehrlich Arsenic based Salvarsan First chemical compound to cure a disease Syphilis Salvarsan Difficult to mix/administer Many side effects Gerhard Domagk Discovered 1935 Sulfonamide Synthetic red dye 1 st commercially available antibacterial Prontosil 3
Alexander Fleming Discovered 1928 Penicillin Howard Florey & Ernst Chain Purified and mass produced Introduced 1942 Nature Reviews Microbiology 5, 175-186 (March 2007) New Antibiotics 16 14 12 10 8 6 4 2 0 '83-'87 '88-'92 '93-'97 '98-'02 '03-'07 '08-'11 4
Penicillin Armstrong, G. L. et al. JAMA 1999;281:61-66 US Antibiotic Usage Much is unknown Humans ~120 million outpatient & ~ 50 million inpatient Rx/y ~ 3 million lbs/y Animal agriculture ~ 24.6 million lbs/y Source: Mellon, M, et al, Hogging It, Estimates of Antimicrobial Abuse in Livestock Union of Concerned Scientists, January 2001 Nontherapeutic Growth promoters Agricultural Use Mechanism and total effect not clear Majority of antibiotics Therapeutic Treat illness Prophylaxis 5
What s the Harm? Resistant organisms shed into environment: Through food chain Direct contact &/or contamination of water and fields Resistant organisms include: Salmonella, Campylobacter, Klebsiella pneumoniaie, Enterococcus faecium, Escherichia coli (ESBL), MRSA Human Use ~ 50% of all antibiotics are unnecessarily or inappropriately prescribed Antibiotic Misuse Not needed Continued longer than necessary Wrong dose Broad spectrum instead of narrow Wrong Ab chosen 6
What s the Harm? The Individual Antibiotic use may be associated with: Cost Side effects C. difficle infection Colonization/infection with resistant organism C. difficile Antibiotic exposure is most important risk factor for Clostridium difficile associated disease (CDAD) Up to 85% of patients with CDAD had antibiotic exposure in the 28 days before infection Epidemic strain (NAP-1/BI ) of C. difficile Resistant to flouroquinolones Hospital Acquired C. difficile ~ 1% of inpatients had hospital acquired CDAD ~10% of those with CDAD died ~3 fold increase in hazard of death Arch Intern Med. 2010;170:1804-1810 7
C. difficle Incidence & Mortality # of CDAD Cases per 100,000 Discharges Annual Mortality Rate per Million Population Year Elixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April 2008. Available at: http://www.hcupus.ahrq.gov/reports/statbriefs/sb50.pdf. Accessed November 7, 2011. Redelings MD, et al. Emerg Infect Dis. 2007;13:1417-1419. Individual Antibiotic Resistance Antibiotic use resistance of urinary/respiratory bacteria to those antibiotics Antibiotics may impact on bacterial resistance for up to 12 months The greater the number or duration of antibiotic courses prescribed in the previous 12 months, the greater the likelihood that resistant bacteria will be isolated from patient Resistance in respiratory tract bacteria and previous antibiotic prescribing Costelloe C et al. BMJ 2010;340:bmj.c2096 2010 by British Medical Journal Publishing Group 8
Resistance in urinary tract bacteria (E coli) and antibiotic exposure Costelloe C et al. BMJ 2010;340:bmj.c2096 2010 by British Medical Journal Publishing Group Resistance in respiratory tract streptococci of healthy volunteers and previous antibiotic prescribing Costelloe C et al. BMJ 2010;340:bmj.c2096 2010 by British Medical Journal Publishing Group Cost for Rx 50% inappropriate What s the Harm? The Collective morbidity & mortality from resistant organisms costs from treating these infections We all may need an antibiotic one day 9
Increasing Antibiotic Resistance Acinetobacter Gonorrhea Group B streptococcus Extended-spectrum -lactamase (ESBL) GN bacteria Klebsiella, E. Coli Methicillin resistant Staphylococcus aureus (MRSA) Neisseria meningitidis Salmonella Shigella Streptococcus pneumoniae (DRSP) Tuberculosis Vancomycin-resistant Enterococci (VRE) Vancomycin-Intermediate/Resistant Staphylococcus aureus (VISA/VRSA) Viral HIV Non-Bacterial Resistance Influenza Fungus Candida Parasitic Malaria For Example Penicillin Resistance in S. pneumoniae United States 1979-2003 vaccine 30 Perecent of isolates 25 20 15 10 5 Intermediate Fully Resistant Sentinel ABCs 0 1979 1982 1985 1988 1991 1994 1997 2000 2003 1979-1994: CDC Sentinel Surveillance Network Year 1995-2003: CDC Active Bacterial Core Surveillance (ABCs) /Emerging Infections Program 10
Inpatient 50% Unnecessary Pt may appear to have (or possibly have) infection treatable by antibiotics Pneumonia, Urinary tract infection Lack of knowledge: Unnecessary duplication of therapy Overly broad spectrum Lack of time Outpatient 50% Unnecessary Quicker to write Rx than to explain why Diagnostic uncertainty Malpractice Broader spectrum overused Newer=better, Pharm reps Perceived & actual patient expectations Do something What s the Harm? Cultural/Regional Effects 11
Over Prescribing Doctors Veterans Less academically inclined Busier not better Poorer diagnosticians 12
Outpatient Strategies No magic bullet Small changes with: Guidelines, didactic educational meetings, peer review Outpatient Strategies Bigger changes with: Interactive workshops, educational outreach, MD reminders Multifaceted intervention with education to MDs, patients, general population Delayed prescriptions 13
CDC Get Smart Campaign Antimicrobial Stewardship Inpatient Goals Appropriate use of Abs leading to: emergence of resistance patient safety adverse effects including C. dificile Save money ID specialist Antimicrobial Stewardship Team Clinical PharmD with ID training Clinical microbiologist Information system specialist Infection control preventionist Hospital epidemiologist 14
Core Strategies Prospective audit with intervention & feedback Academic detailing when order is received Documented significant reductions in use and cost savings Formulary restriction and preauthorization requirement Have stopped C. dificile outbreaks Led to short-term increased susceptibilities among GN pathogens Long-term beneficial impact not established Education Supplemental Strategies Essential element, marginally effective by itself Guidelines and clinical pathways Incorporation of local resistance patterns helps Antimicrobial cycling Insufficient data Antimicrobial order forms Automatic stop orders and MD justification Supplemental Strategies Streamlining or de-escalation of therapy Narrowing Rx based on Cx results Dose optimization Individualize dose for patient/condition Parenteral to oral conversion Earlier changes faster discharge Computer assistance Provides patient-specific data at point of care 15
Antimicrobial Stewardship has been shown to decrease C. dificile infections Impact of fluoroquinolone restriction on rates of C. difficle infection HO-CDAD cases/1,000 pd 2.5 2 1.5 1 0.5 0 2005 2006 Month and Year 2007 Infect Control Hosp Epidemiol. 2009 Mar;30(3):264-72. Save money. 16
Savings of $200,000-$900,000/year Active Management Passive Management Carling et. al. CID,1999;29;1189. And reduce resistance P. aeruginosa susceptibilities before and after implementation of antibiotic restrictions CID 1997;25:230 P<0.01 for all increases 17
NJDHSS New Jersey Careful Antibiotic Use Strategies and Education (NJ CAUSE) Multidisciplinary task force - 2005 Strategic plan to combat antimicrobial resistance 5 Focus areas Surveillance Statewide antibiogram Education NJ CAUSE Conferences, Get Smart, academic detailing Infection Control\Best Practices Determine best practices and disseminate information Laboratory Standardized antimicrobial susceptibility testing Economics Demonstrate cost-savings from stewardship programs Antimicrobial Stewardship Protecting a Valuable Resource November 8, 2011 Medical Director Communicable Disease Service NJDHSS Edward.Lifshitz@doh.state.nj.us (609) 826-5964 18