Overview Antibiotic resistance – a global issue The link between antibiotic use and resistance Addressing antibiotic resistance The role of antimicrobial stewardship Actions for Antibiotic Awareness Week 2013 – 7 days, 7 ways to improve antibiotic use in our hospital This presentation will cover: The problem of antibiotic resistance today That it is a critical patient safety and public health issue How extensive the problem is The link between the antibiotic use and the development of resistance. The role of antimicrobial stewardship in supporting the appropriate use of antibiotics Information on antibiotic awareness week in Australia and internationally and the focus on preserving the miracle of antibiotics while there is still time 2

Antibiotics are a limited resource We have….. Growing rates of resistance Inappropriate use Decreasing pipeline of new antibiotics Declining FDA approvals of new antibiotics in United States1 We have a problem: There are growing rates of resistance to antibiotics in our hospitals and the community The antibiotics we do have, we are not using appropriately There are few new antibiotics being developed 1. Accessed from www.idsociety.org, from Spellberg, CID 2004 (modified) 3

The “miracle” of antibiotics Discovery of penicillin by Sir Alexander Fleming and its subsequent development by Florey & Chain revolutionised treatment of infectious disease Life expectancy has ↑ due to ability to treat infection Crude mortality rates for all causes, noninfectious causes and infectious diseases over the period 1900-1996. The most significant impact on increasing life expectancy in the last 100 years has been the ability to prevent infection through improvements in public health, such as sanitation, and vaccinations and to treat infection with antibiotics. Mortality rates from non infectious diseases has remained fairly constant whilst dying from infectious diseases has decreased markedly, although more recently this is starting to increase. The red line depicts falling mortality rates due to infection. The spike around 1920 was due to an influenza epidemic. 2. Armstrong GL et al, JAMA 1999;281(1):61-66 4

“Anne Miller, 90, first patient who was saved by penicillin” In 1999, the New York Times published an article about Anne Sheafe Miller…. “…who made medical history as the first patient ever saved by penicillin…died on May 27 in Salisbury, Conn. She was 90…..” March 1942 - Mrs Miller was near death, suffering from a streptococcal infection. Doctors had tried everything available (sulfa drugs, blood transfusions, surgery). All treatments failed. Desperate, doctors obtained a tiny amount of what was still an obscure, experimental drug and injected Mrs Miller with it. Her hospital chart (now an exhibit at the Smithsonian Institution), registered a sharp overnight drop in temperature, and by the next day she was rapidly recovering. Mrs Miller's life was saved by antibiotics. Penicillin also saved the lives of all those previously felled by bacterial infections with streptococci, staphylococci and pneumococci, and the lives of an untold number of servicemen and civilians wounded in World War II. 3. Saxon W, New York Times, June 9, 1999 5

Antibiotics continue to save lives every day… Ability to control infection is critical to other advances in medicine Neonatal care Transplantation Chemotherapy for malignancy Immunosuppression Safe surgery Safe obstetric care Intensive care interventions Advances in modern medicines such as transplantation, neonatal care, cancer treatments, safe surgery and obstetric care and ICU interventions all rely on effective antibiotics to control infection. Without antibiotics these therapies will be endangered and our most vulnerable patients put at risk. 6

Emergence of antibiotic resistance “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.” Sir Alexander Fleming, 1945 The issue of antibiotic resistance was recognised early in the ‘antibiotic era’. It threatens our ability to control infection. 4. Sir Alexander Fleming, Nobel Lecture, December 1945 7 7

Emergence of antibiotic resistance Antibiotic resistance threatens ability to control infection The time it takes for bacteria to develop resistance is decreasing. Start of line = time of antibiotic discovery, End of line = when resistance reported More recently the time between discovery and development of resistance has become much shorter. 5. Pray LA Insight Pharma Reports 2008, in Looke D ‘The Real Threat of Antibiotic Resistance’ 2012 8

Resistance spreads rapidly Once resistance develops it spreads rapidly. This graph from the Center of Disease Control in the US demonstrates how quickly resistant strains of MRSA, VRE and fluoroquinolone resistant Pseudomonas aeruginosa have spread. 6. Centers for Disease Control and Prevention http://www.cdc.gov/hai/ 9

“The Red Plague” Refers to emerging resistance in Gram negative organisms (E. coli, Klebsiella spp.) Cause common infections e.g. UTI in community High rates of resistance in Asia-Pacific region Some strains pan-drug resistant Multi resistant gram negative bacteria have developed a high level of resistance to antibiotics. Although rates are lower in Australia than in the United States, southern Europe and much of Asia, gram-negative resistance in Australia is rising. This article from the MJA in March of this year (2013) suggests that establishment of gram-negative resistance in Australia may have several consequences, including the need to treat previously simple infections, such as uncomplicated urinary tract infections, with intravenous instead of oral antimicrobial therapy; the need to treat severe community-acquired sepsis with antibiotics of last resort upfront, a growing ineffectiveness of surgical antibiotic prophylaxis. 7. Looke DF, Gottlieb T, Jones CA, Paterson DL Med J Aust. 2013 Mar 18;198(5):243-4. 10

Real people are affected No one is immune from the risk of infection with a multi-resistant pathogen. Last year we described 19 year old David Ricci’s struggle with a horrific multi-resistant pathogen, which was featured on the ABC’s Four Corners Program “Rise of the Superbugs”. But there are more, many more patient stories. 8. IDSA ‘Patient stories’ 2013 http://www.idsociety.org/Patient_Stories/ 11 11

Impact of resistance Increased morbidity/ mortality Evidence across many pathogens Untreatable infections Now being encountered Increased costs9 $18-29,000 US/patient Excess length of stay 6.4 – 12.7 days/patient Patients infected with resistant pathogens are more likely to have treatment failures, recurrent infections and delayed recovery. A two fold higher death rate has been reported amongst patients with antimicrobial- resistant infections. There is also a significant cost related to the treatment of resistant infections – to patients and to the health care system. 9. Roberts RR et al. Clinical Infectious Diseases 2009; 49:1175-1184 12

Resistance (%ESBL) in the Asia Pacific region Korea ECOL: 37% KPNE: 40% China* ECOL: 54% KPNE: 41% Japan† ECOL: 17% KPNE: 11% Hong Kong ECOL: 46% KPNE: 23% India ECOL: 78% KPNE: 64% Taiwan ECOL: 91% KPNE: 75% Thailand* ECOL: 55% KPNE: 50% Philippines ECOL: 47% KPNE: 23% Singapore ECOL: 21% KPNE: 32% Malaysia ECOL: 36% KPNE: 45% At the moment we have no consistent model for monitoring anti microbial resistance in Australia. There is a need to develop a comprehensive strategy to address AMR. We do have some information, for example this slide is from a recent presentation at a meeting of the Australasian Society for Infectious Diseases describing the extent of gram negative resistance in the Asia Pacific region (courtesy of Prof John Turnidge). The figures depicted here show the extended-spectrum β-lactamases (ESBL) phenotype rates for pathogens E Coli (ECOL) & Klebsiella pneumoniae (KPNE) i.e. proportion of resistance. Of note, ESBLs and also Carbapenemases are potent indicators of multi-resistance. Indonesia ECOL: 71% KPNE: 64% Australia ECOL: 12% KPNE: 15% New Zealand ECOL: 11% KPNE: 10% 10. Mendes et al., Antimicrob. Agents Chemother. 2013 11. *Xiao et al, Drug Resist Updat, 2011 (2009 data) 12. †Chong et al., EJCMID, 2011 (2009 data) 13

Resistance in Australia gains public attention… We need to act now!! 14

Antibiotic resistance locally Which infections are we seeing ? What are our susceptibility and resistance patterns ? [Insert hospital data] [Numbers of cases] [Examples of cases] Note: Users should insert local hospital data into this slide. If a hospital antibiogram is available, use that. If not, give examples of infections from resistant pathogens that have occurred. Examples might include: central line associated bacteraemia, catheter associated urinary tract infections, surgical site infections. Consider including information about increased length of stay and negative outcomes for patients. 15

The link between antibiotic resistance and antibiotic use Countries with high penicillin consumption also have high rates of penicillin resistance in pneumococci Occurrence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) versus outpatient use of penicillins in 17 European countries.  Here we see the occurrence of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) plotted against outpatient use of penicillins in 17 European countries. DID = defined daily doses per 1,000 inhabitants.  This clearly demonstrates the relationship of usage with development of penicillin resistance – as usage has increased so has resistance . 13. van de Sande-Bruinsma N et al. Emerging Infectious Diseases 2008; 14(11):1722-1730 16 16

Antibiotic usage varies between hospitals Even within a country – huge inter-hospital variation in antibiotic consumption e.g. Meropenem use – 10-fold variation across 52 Australian hospitals National Antimicrobial Utilisation Surveillance Program (NAUSP) 2012-13 annual report14 Even within a country there is inter-hospital variation in consumption of antibiotics and not easily accounted for by case-mix. For example, this slide from NAUSP (shows a 10-fold variation in Meropenem use across 52 Australian hospitals (Hospitals are mostly large tertiary institutions). Axis label: Antimicrobial usage rate DDD per 1000 OBDs = Defined Daily Doses per 1000 Occupied Bed Days Consider that Meropenem is a carbapenem. Carbapenems are the last line of treatment for serious infections caused by multi resistant E.coli, Klebsiella speciies and other Enterobacteriaceae. Gram negative bacteria known as carbapenem resistant Enterobacteriaceae (CRE) that are resistant to most types of antibiotics including carbapenems are now emerging. Note – in addition to high consumption, there is evidence to suggest that up to 50% of antibiotic prescribing in Australian Hospitals is not in accord with guidelines (see Antimicrobial Stewardship in Australian Hospitals , 2011 ) 14. South Australian Infection Control Service. National Antimicrobial Utilisation Surveillance Program (NAUSP) 2012-13 Annual Report. 17 17

What is inappropriate use ? Unnecessary prescription of antibiotics, such as for viral infections (colds) or for prolonged prophylaxis Using broad-spectrum antibiotics (such as third generation cephalosporins, carbapenems) when narrow-spectrum antibiotics are effective Prescribing too low or too high a dose Continuing treatment for longer than necessary Not prescribing according to microbiology results Omitting or delaying administration of doses Prescribing intravenous therapy when oral therapy is known to be effective and clinically safe Not taking antibiotics as prescribed With inappropriate antibiotic usage recognised as a key driver of resistance and few new drugs in the pipeline, it is apparent that interventions to promote appropriate use are an essential component of an overall strategy to reduce antibiotic resistance. In human health, up to 50% of antibiotic prescriptions in Australia are inappropriate and hospital use is higher compared to northern European countries. This slides gives some examples of inappropriate use Unnecessary prescription of antibiotics, such as for viral infections (colds) or for prolonged prophylaxis Use of broad-spectrum antibiotics (such as third generation cephalosporins, carbapenems) when narrow-spectrum antibiotics are effective Inadequate treatment. For example, the antibiotic is ineffective or the dose is too low leading to treatment failure Prescribing too high a dose, causing toxicity Continuing treatment for longer than necessary because courses are not time limited or cancelled Not prescribing according to microbiology results Omitting doses or delays in administration Prescribing intravenous agents when an oral agent is known to be as effective and clinically safe Not taking antibiotics as prescribed – this may include stopping and starting therapy, continuing for shorter or longer than prescribed, saving antibiotics for another illness, or giving “leftover” prescriptions or antibiotics to others who are sick.

Antibiotic usage in our hospital Insert local usage data if available Note: This information should be available from the Pharmacy Department or local pharmacy contractor/supply service. If comprehensive data is not readily available, consider choosing one broad spectrum agent as an example. 19

Antibiotics are a limited resource Few new antibiotics being developed Most classes developed pre 1970 Only 3 novel systemic classes in last 20 years Growing recognition globally that: new antibiotics are urgently required we need to conserve what we have To add to the problem of increased resistance and consumption, few new antibiotics are being developed. only three novel antibiotic classes have been developed in the last 20 years. although new antibiotics are urgently needed it is expected that few will be developed in the next 10 years. there is a need to conserve what we have.

In short…we have a problem ! Growing rates of resistance Inappropriate use Decreasing pipeline of new antibiotics In summary we have a problem: There are growing rates of resistance to antibiotics in our hospitals and the community There are few new antibiotics being developed What antibiotics we do have we are not using appropriately 15. Turnidge J et al. MJA 2009: 191(7): 368-373

Addressing Antibiotic Resistance in Australia – “One Health” Involves cooperation between human health professionals, veterinarians, farmers, policy makers from health and agriculture and other related experts to develop strategies to contain antibiotic resistance National work has commenced to progress a “One Health” approach in Australia, through an Antimicrobial Resistance Prevention & Containment Strategy.

Addressing Antibiotic Resistance in our hospital Infection prevention and control Hand hygiene Standard and transmission based precautions Environmental cleaning Aseptic technique Workforce immunisation Antimicrobial stewardship Addressing antibiotic resistance requires a multi-pronged approach combining a range of strategies including antimicrobial stewardship. Antimicrobial management or stewardship programs have been developed in response to the need to reduce unnecessary and inappropriate antibiotic use. However an AMS program alone is not sufficient to control resistance. To be effective a program needs to be established in conjunction with a comprehensive infection prevention and control program that includes hand hygiene, standard and transmission based precautions and cleaning and disinfection.

Antimicrobial stewardship (AMS) Aim is to optimise use of antibiotics taking into account: Evidence of efficacy Toxicity Ecologic harm (effect on resistance) Requires team work at all levels: Executive and clinical leadership Prescribers, clinicians, pharmacists Essential elements: treatment guidelines, formulary with restrictions, selective susceptibility reporting of isolates, effective audit and feedback to prescribers Antimicrobial stewardship (AMS) is a systematic approach to optimising the use of antibiotics taking into account: Evidence of efficacy Toxicity of the drug Ecological harm – the effect on resistance or development of Clostridium difficile infection. Successful AMS requires executive support and clinical leadership as well as team work between prescribers, pharmacists and nurses. Essential elements of an AMS program include: Use of treatment guidelines that take into account local microbiological susceptibility patterns An antibiotic formulary that includes restricting board spectrum and later generation antimicrobials to patients in whom use is clinically justified. Selective reporting of susceptibility testing consistent with hospital treatment guidelines Monitoring and auditing antibiotic usage. Reviewing antibiotic prescribing with intervention and feedback to prescribers 24

NSQHS Standards, Standard 3: Antimicrobial Stewardship Criterion Actions required: 3.14.1 An AMS program is in place 3.14.2 The clinical workforce prescribing antimicrobials have access to endorsed Therapeutic Guidelines on antibiotic usage 3.14.3 Monitoring of antimicrobial usage and resistance is undertaken 3.14.4 Action is taken to improve the effectiveness of AMS From January 2013 all hospitals and day procedure services undergoing accreditation will be assessed against the National Safety and Quality Health Service Standards. Standard 3 is the Standard for “Preventing and Controlling Healthcare Associated Infections” . There is an Antimicrobial Stewardship Criterion that forms part of the Standard. Hospitals are required to: Have an AMS program in place Provide access to endorsed Therapeutic Guidelines on antibiotic usage Monitor their antimicrobial usage and resistance; and Take action to improve the effectiveness of their AMS program 16. ACSQHC National Safety & Quality Health Service Standards www.safetyandquality.gov.au/our-work/accreditation/nsqhss/ 25

Antimicrobial Stewardship in our Hospital Local processes for stewardship Include local processes for seeking ID/micro consults and pharmacy advice, any other relevant information.

Our Hospital tools and activities to promote appropriate use of antibiotics AMS committee (or other committee e.g. infection control, drug & therapeutics committees) to coordinate activity Education prescribing guidelines Policy Formulary with restrictions and approval Access to expert prescribing advice ID, Micro, Pharmacy Audits and feedback Who to contact? For hospitals to complete 27

Antibiotic Awareness Week 2013 Coordinated by The Australian Commission on Safety and Quality in Health Care National working group comprises members from: NPS MedicineWise, Australian Pesticides and Veterinary Medicines Authority, Department of Agriculture, State and Territory Health department representatives, Australian Veterinary Association Supported by: Australasian College for Infection Prevention and Control Australasian Society for Infectious Diseases Australian Society for Antimicrobials Society of Hospital Pharmacists of Australia This is the second year that Australia has joined with other developed countries in holding a range of activities in November to raise the awareness of antibiotic resistance and the importance of conserving antibiotic use . Australia’s campaign is coordinated by the Australian Commission on Safety and Quality in Health Care, and supported by NPS MedicineWise Australasian College for Infection Prevention and Control Australasian Society for Infectious Diseases Australian Society for Antimicrobials Society of Hospital Pharmacists of Australia 28

Seven Actions Antibiotic Awareness Week Obtain cultures before starting therapy Use Therapeutic Guidelines: Antibiotic17 Document indication and review date Review and reassess antibiotics at 48 hours Consider IV to oral switch Seek advice for complex cases Educate patients about antibiotic use What else can you do to improve antibiotic use ? Visit www.safetyandquality.gov.au/aaw2013 How can we use antibiotics appropriately? Use microbiology results to improve antibiotic choice, Prescribe in accordance with the latest edition of Therapeutic Guidelines:Antibiotic or hospital guidelines that align with the Therapeutic Guidelines:Antibiotic Document the indication – this enables timely review by the team if required and reminds clinicians to review care. Helps to ensure duration of therapy does not exceed recommendations, enables de-escalation if required. Review therapy at 48 hours. Convert to targeted therapy when the pathogen and its susceptibilities are known. Consult a clinical pharmacist for advice on optimising the antibiotic doses. Change from IV to oral therapy where possible Seek advice from clinical microbiology or infectious diseases physician early for complex cases Ensure patients and their carers know how to use antibiotics appropriately 17. Therapeutic Guidelines: Antibiotic. Version 14. 2010 29

Remember…. Antibiotics are a limited and precious resource Antibiotic resistance is a global problem - in our hospitals and in our communities – and an issue for prescribers and users of antibiotics Resistant infections are harder to treat and are associated with higher rates of mortality and morbidity Inappropriate use of antibiotics drives resistance There are few new antibiotics being made available Antibiotics must always be used responsibly If we don’t all take action today, there may be no cure tomorrow…

Antibiotic Awareness Week in our Hospital Local activities processes for stewardship Include information about local activities. National Antimicrobial Prescribing Survey 2013 Include information about local participation in the survey, and local contact details

Australian Commission on Safety and Quality in Health Care NO ACTION TODAY, NO CURE TOMORROW !* *Adopted from WHO World Health Day, 2011 campaign to address AMR National Antimicrobial Prescribing Survey Online prescribing survey conducted by the NHMRC/Melbourne Health AMS Research Group, supported by the Commission Option for benchmarking analysis Can be accessed via the Commission webpage www.safetyandquality/AAW2013 The Commission has adopted the tagline utilised for the World Health Organsition’s World Health Day 2011 campaign to address antimicrobial resistance. The Commission has information about antimicrobial resistance (AMR) and actions to address the problem on it’s website, as well as a number of resources to support antimicrobial stewardship. There are also links to national and international organisations participating in Antibiotic Awareness Week 2013.

NPS MedicineWise Visit nps.org.au/antibiotics to access resources for health professionals and consumers. Become an antibiotic resistance fighter: take the health professional pledge. Paint your ward purple – wear a ‘Resistance Fighter’ t-shirt and spread the word. Join the conversation on twitter @NPSMedicineWise or facebook.com/npsmedicinewise. NPS MedicineWise is encouraging all health professionals to pledge to join the fight against antibiotic resistance. A new interactive application on the NPS MedicineWise website will allow people to pledge their commitment to the MINDME creed and add the suburb of their workplace to the national map of antibiotic resistance fighters. After making the pledge, individuals will be able to generate a personalised antibiotic resistance fighter certificate to print and display in their hospital, clinic or office, or share with social media networks. The first 3000 – 5000 health professionals to pledge to join the fight against antibiotic resistance will also be able to order a free resistance fighter t-shirt to wear during Antibiotic Awareness Week. The pledge is available on-line along with other resources, visit www.nps.org.au/antibiotics

A global effort European Antibiotic Awareness Day http://ecdc.europa.eu/en/eaad/Pages/Home.aspx Canadian Antibiotic Awareness Week http://antibioticawareness.ca/ United States Get Smart About Antibiotics Week http://www.cdc.gov/GetSmart/campaign-materials/week/index.html

Acknowledgements and References Australian Commission on Safety and Quality in Health Care AMS Jurisdictional Network Antibiotic Awareness Week working group members AMS Advisory Committee Australian Group on Antimicrobial Resistance National Antimicrobial Utilisation Surveillance Program NHMRC/ Melbourne Health Antimicrobial Stewardship Research Group European Centre for Disease Prevention and Control World Health Organization (WHO), World Health Day Campaign 2011 http://www.who.int/world-health-day/2011/en/index.html. This presentation is endorsed only when presented in it’s original version. The original version along with a complete list of references can be downloaded from the Commission web page: www.safetyandquality/AAW2013