OverviewAntibiotic resistance a global issue The link between antibiotic use and resistanceAddressing antibiotic resistanceThe role of antimicrobial stewardshipActions for Antibiotic Awareness Week 2013 7 days, 7 ways to improve antibiotic use in our hospital

Antibiotics are a limited resourceWe have..Growing rates of resistanceInappropriate useDecreasing pipeline of new antibiotics

1. Accessed from www.idsociety.org, from Spellberg, CID 2004 (modified)

Declining FDA approvals of new antibiotics in United States1

The miracle of antibiotics 2. Armstrong GL et al, JAMA 1999;281(1):61-66 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 infectionCrude mortality rates for all causes, noninfectious causes and infectious diseases over the period 1900-1996.

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 penicillindied 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

Antibiotics continue to save lives every dayAbility to control infection is critical to other advances in medicine

Neonatal careTransplantationChemotherapy for malignancyImmunosuppressionSafe surgerySafe obstetric careIntensive care interventions

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

Emergence of antibiotic resistanceAntibiotic resistance threatens ability to control infection

5. Pray LA Insight Pharma Reports 2008, in Looke D The Real Threat of Antibiotic Resistance 2012

Resistance spreads rapidly6. Centers for Disease Control and Prevention http://www.cdc.gov/hai/

The Red PlagueRefers to emerging resistance in Gram negative organisms (E. coli, Klebsiella spp.) Cause common infections e.g. UTI in communityHigh rates of resistance in Asia-Pacific region Some strains pan-drug resistant7. Looke DF, Gottlieb T, Jones CA, Paterson DL Med J Aust. 2013 Mar 18;198(5):243-4.

Real people are affected

8. IDSA Patient stories 2013 http://www.idsociety.org/Patient_Stories/

Impact of resistance

Increased morbidity/ mortalityEvidence across many pathogens Untreatable infections Now being encounteredIncreased costs9$18-29,000 US/patientExcess length of stay 6.4 12.7 days/patient

9. Roberts RR et al. Clinical Infectious Diseases 2009; 49:1175-1184

Resistance (%ESBL) in the Asia Pacific regionAustraliaECOL: 12%KPNE: 15%New ZealandECOL: 11%KPNE: 10%Hong KongECOL: 46%KPNE: 23%IndiaECOL: 78%KPNE: 64%IndonesiaECOL: 71%KPNE: 64%JapanECOL: 17%KPNE: 11%KoreaECOL: 37%KPNE: 40%MalaysiaECOL: 36%KPNE: 45%PhilippinesECOL: 47%KPNE: 23%SingaporeECOL: 21%KPNE: 32%TaiwanECOL: 91%KPNE: 75%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)China*ECOL: 54%KPNE: 41%Thailand*ECOL: 55%KPNE: 50%

Resistance in Australia gains public attentionWe need to act now!!

Antibiotic resistance locally Which infections are we seeing ? What are our susceptibility and resistance patterns ? [Insert hospital data] [Numbers of cases] [Examples of cases]

The link between antibiotic resistance and antibiotic use Countries with high penicillin consumption also have high rates of penicillin resistance in pneumococci13. van de Sande-Bruinsma N et al. Emerging Infectious Diseases 2008; 14(11):1722-1730Occurrence of penicillin-nonsusceptibleStreptococcus pneumoniae(PNSP) versus outpatient use of penicillins in 17 European countries.

Antibiotic usage varies between hospitalsEven within a country huge inter-hospital variation in antibiotic consumption e.g. Meropenem use 10-fold variation across 52 Australian hospitals

14. South Australian Infection Control Service. National Antimicrobial Utilisation Surveillance Program (NAUSP) 2012-13 Annual Report. National Antimicrobial Utilisation Surveillance Program (NAUSP) 2012-13 annual report14

What is inappropriate use ?Unnecessary prescription of antibiotics, such as for viral infections (colds) or for prolonged prophylaxisUsing broad-spectrum antibiotics (such as third generation cephalosporins, carbapenems) when narrow-spectrum antibiotics are effectivePrescribing too low or too high a dose Continuing treatment for longer than necessary Not prescribing according to microbiology resultsOmitting or delaying administration of dosesPrescribing intravenous therapy when oral therapy is known to be effective and clinically safe Not taking antibiotics as prescribed

Antibiotic usage in our hospital

Insert local usage data if available

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 requiredwe need to conserve what we have

In shortwe have a problem !

Growing rates of resistanceInappropriate useDecreasing pipeline of new antibiotics

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 resistanceNational 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 controlHand hygieneStandard and transmission based precautionsEnvironmental cleaningAseptic technique Workforce immunisationAntimicrobial stewardship

Antimicrobial stewardship (AMS)Aim is to optimise use of antibiotics taking into account:Evidence of efficacyToxicityEcologic harm (effect on resistance) Requires team work at all levels:Executive and clinical leadershipPrescribers, clinicians, pharmacists

Essential elements: treatment guidelines, formulary with restrictions, selective susceptibility reporting of isolates, effective audit and feedback to prescribers

NSQHS Standards, Standard 3: Antimicrobial Stewardship CriterionActions required:

3.14.1 An AMS program is in place 3.14.2 The clinical workforce prescribing antimicrobials have access to endorsedTherapeutic Guidelines on antibiotic usage 3.14.3 Monitoring of antimicrobial usage andresistance is undertaken 3.14.4 Action is taken to improve the effectiveness of AMS16. ACSQHC National Safety & Quality Health Service Standards www.safetyandquality.gov.au/our-work/accreditation/nsqhss/

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 antibioticsAMS committee (or other committee e.g. infection control, drug & therapeutics committees) to coordinate activityEducationprescribing guidelinesPolicyFormulary with restrictions and approvalAccess to expert prescribing adviceID, Micro, PharmacyAudits and feedbackWho to contact?

Antibiotic Awareness Week 2013Coordinated 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 DiseasesAustralian Society for AntimicrobialsSociety of Hospital Pharmacists of Australia

Seven Actions Antibiotic Awareness Week Obtain cultures before starting therapy Use Therapeutic Guidelines: Antibiotic17Document indication and review date Review and reassess antibiotics at 48 hoursConsider IV to oral switch Seek advice for complex casesEducate patients about antibiotic use

What else can you do to improve antibiotic use ?

Visit www.safetyandquality.gov.au/aaw2013

17. Therapeutic Guidelines: Antibiotic. Version 14. 2010

Remember. Antibiotics are a limited and precious resourceAntibiotic resistance is a global problem - in our hospitals and in our communities and an issue for prescribers and users of antibioticsResistant 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 availableAntibiotics must always be used responsibly If we dont 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 2013Include information about local participation in the survey, and local contact details

Australian Commission on Safety and Quality in Health CareNO 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 CommissionOption for benchmarking analysis Can be accessed via the Commission webpage www.safetyandquality/AAW2013

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.

A global effort European Antibiotic Awareness Day http://ecdc.europa.eu/en/eaad/Pages/Home.aspxCanadian 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 CareAMS Jurisdictional Network Antibiotic Awareness Week working group membersAMS Advisory CommitteeAustralian Group on Antimicrobial Resistance National Antimicrobial Utilisation Surveillance ProgramNHMRC/ Melbourne Health Antimicrobial Stewardship Research Group European Centre for Disease Prevention and ControlWorld 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 its original version. The original version along with a complete list of references can bedownloaded from the Commission web page: www.safetyandquality/AAW2013

*This presentation will cover:The problem of antibiotic resistance todayThat it is a critical patient safety and public health issueHow extensive the problem isThe link between the antibiotic use and the development of resistance. The role of antimicrobial stewardship in supporting the appropriate use of antibioticsInformation on antibiotic awareness week in Australia and internationally and the focus on preserving the miracle of antibiotics while there is still time*We have a problem:There are growing rates of resistance to antibiotics in our hospitals and the communityThe antibiotics we do have, we are not using appropriatelyThere are few new antibiotics being developed*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. **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.

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*The time it takes for bacteria to develop resistance is decreasing.Start of line = time of antibiotic discovery, End of line = when resistance reportedMore recently the time between discovery and development of resistance has become much shorter.

**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. 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. **No one is immune from the risk of infection with a multi-resistant pathogen. Last year we described 19 year old David Riccis struggle with a horrific multi-resistant pathogen, which was featured on the ABCs Four Corners Program Rise of the Superbugs. But there are more, many more patient stories.

**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. 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 -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.

***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.

*Here we see the occurrence of penicillin-nonsusceptibleStreptococcus 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 .

**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 )*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 prophylaxisUse of broad-spectrum antibiotics (such as third generation cephalosporins, carbapenems) when narrow-spectrum antibiotics are effectiveInadequate treatment. For example, the antibiotic is ineffective or the dose is too low leading to treatment failurePrescribing too high a dose, causing toxicityContinuing treatment for longer than necessary because courses are not time limited or cancelledNot prescribing according to microbiology resultsOmitting 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. *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. 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 summary we have a problem:There are growing rates of resistance to antibiotics in our hospitals and the communityThere are few new antibiotics being developedWhat antibiotics we do have we are not using appropriatelyAddressing 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) is a systematic approach to optimising the use of antibiotics taking into account:Evidence of efficacyToxicity of the drugEcological 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 patternsAn 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 guidelinesMonitoring and auditing antibiotic usage.Reviewing antibiotic prescribing with intervention and feedback to prescribers

*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 placeProvide access to endorsed Therapeutic Guidelines on antibiotic usageMonitor their antimicrobial usage and resistance; andTake action to improve the effectiveness of their AMS program

*For hospitals to complete*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 . Australias campaign is coordinated by the Australian Commission on Safety and Quality in Health Care, and supported by NPS MedicineWiseAustralasian College for Infection Prevention and Control Australasian Society for Infectious DiseasesAustralian Society for AntimicrobialsSociety of Hospital Pharmacists of Australia

*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 casesEnsure patients and their carers know how to use antibiotics appropriately The Commission has adopted the tagline utilised for the World Health Organsitions World Health Day 2011 campaign to address antimicrobial resistance.

The Commission has information about antimicrobial resistance (AMR) and actions to address the problem on its 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 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