Antibiotic Resistance. A global view. Katia ISKANDAR RPh, Pharm.D, MHS, AMES, PhD candidate

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1 Antibiotic Resistance A global view Katia ISKANDAR RPh, Pharm.D, MHS, AMES, PhD candidate

2 Learning objectives Explore antibiotics and resistance from a historical perspective Have an insight into the current situation and where we are heading Discuss the challenges and consequences of antibiotic resistance Learn about new models addressing antibiotic resistance

3 ANTIBIOTIC AND RESISTANCE from a Historical perspective

4 Professor Alexander Fleming at work in his laboratory at St Mary's Hospital, London (1944). By Ministry of Information Photo Division Photographer [Public domain], via Wikimedia Commons. When I woke up just after dawn on September 28, 1928, I certainly didn t plan to revolutionize all medicine by discovering the world s first antibiotic, or bacteria killer. But I guess that was exactly what I did.

5 Nobel Prize in Physiology or Medicine

6 One of the FIRST to urge caution over the new drug was actually Fleming himself!!!!! In his Nobel lecture in 1945, Fleming presciently warned about the dangers of misusing penicillin: 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. The time may come when penicillin can be bought by anyone in the shops.then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.

7 Antibiotic use is a key driver for antibiotic resistance The vicious circle of antibiotic resistance Futurelearn.com

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9 Antibiotics has been available for most part of the world for 70 years

10 Resistance New ANTIBIOTICS A failed model Overuse Marketed Professor Otto Cars. Uppsala University

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13 Antibiotic resistance The Chief Medical Officer of England, Dame Sally Davies, has described the threat of antibiotic resistance as just as important and deadly as climate change and international terrorism.

14 ANTIBIOTIC AND RESISTANCE The problem today

15 All health systems are relying on the availability of effective antibiotics Antibiotics are the pillars, the cornerstones of all medicine Wound infection Urinary tract infection Pneumonia Blood infections Preterm babies Gonorrhea Complicated deliveries Cancer treatments Organ transplants Hip replacements Basic medicine Maternal and child health Modern medicine

16 The secondary health effects of Antibiotic Resistance: A return to the dark age of medicine? Despite many medical professionals considering the secondary effects of Antibiotic Resistance to be the greatest risk, there remain Many unknowns, which have meant that few major studies have looked comprehensively at this impact

17 The consequences of antibiotic resistance move FAR BEYOND HEALTH

18 A global issue There is considerable variation globally in the patterns of AMR, with different countries often experiencing different major problems In modern, well-funded healthcare systems, obtaining access to second and third-line treatments may often not be an issue, mortality rates for patients with infections caused by resistant bacteria are significantly higher, asaretheircosts of treatment The threat of increasingly drug-resistant infections is no less severe in poorer countries. Emerging resistance to treatments for other diseases, such as TB, malaria and HIV, have enormous impacts in lower-income settings

19 An ethical dilemma The Ethics of Drug and Diagnostic Tool Development The Ethics of Antimicrobial Stewardship The Ethics of Ignorance and Behavior Change The Ethics of Priority Setting and Resource Allocation Obligations to Future Generations

20 Health burden of antibiotic resistance In 2014, the World Health Organization (WHO)published the first global report on surveillance of antibiotic resistance The report looks at data from 114 countries and reveals that antibioticresistant bacteria currently claim at least 50,000 lives each year across Europe and the US alone. This is, however, the top of an iceberg as only seven selected bacteria were included in the report.

21 Source: Review on Antimicrobial Resistance.

22 Source: Review on Antimicrobial Resistance.

23 Economic burden of antibiotic resistance Antibiotic resistance is also a huge economic burden for health care and society at large. The overall societal costs of antibiotic-resistant infections are estimated to be 1.5 billion per year in EU and up to $55 billion per year in the US. Review on Antimicrobial Resistance claim that the true cost could increase up to $100 trillion ( trillion) by 2050.

24 Example of calculated additional costs as well as additional days in hospital due to treatment of resistant bacteria Infect Control Hosp Epid 2010; 31: ;Clinical Infect Dis 2009; 49: ; Agents Chemother : December 2009, Volume 4, Issue 12.; Agents Chemother. 2012, 56(1):420 A fact sheet from ReAct - Action on Antibiotic Resistance, May 2012

25 Source: Review on Antimicrobial Resistance.

26 UK charity Nesta

27 UK charity Nesta

28 UK charity Nesta

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30 UK charity Nesta

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32 Antibiotic use in the animal sector In most cases, antibiotics are administered to healthy animals for growth promotion or prevention of disease rather than for therapeutic purposes. Antibiotics are sometimes used to compensate for poor farming practices and are expected to improve production AMR-Review, 2015 and EMA, 2015

33 Understanding Antibiotic resistance

34 Antibiotic resistance is a natural phenomenon It s a bacterial evolution Bacteria are the direct descendants of the first organisms that lived on Earth, with fossil evidence going back about 3.5 billion years

35 Bacteria, these tiny single-celled organisms: Friends or Foe????? Genetic Science Learning Center (University of Utah)

36 The microbiota :our forgotten organ Billions of bacteria inside and on the human body, referred to as the normal flora Weigh approximately two kilos Surprisingly stable over time, BUT Immunity Nutrition Organs development Maintenance of protective barriers Other functions Charis Tsevis/Flickr, CC BY-NC-ND

37 Resistance strategies in bacteria Courtesy of Dr. E. Gullberg.

38 Courtesy of Dr. E. Gullberg

39 Complex problems need complex solutions..

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41 Government part The WHO Global Action Plan asks and urges all countries to put up a national action plan: Surveillance and monitoring Prevention to decrease the need for antibiotics Rational use and access Research Addressing the non-human side, the animal side and also the environmental side

42 Why don't we simply develop new antibiotics? Research and development Profitability issues Safety issues Efficacy issues

43 Alternatives to antibiotics Before the discovery of antibiotics, serum from immune individuals was transferred to infected people as a mode of treatment. The procedure was at that time associated with toxic side-effects, although it seemed rather effective. Today, a sophisticated variant of this strategy, known as antibody therapy, is considered a rather promising alternative to antibiotics. A drawback with this and many other alternatives is that they are not suitable for treating severe infections that need to be handled rapidly

44 Alternatives to antibiotics Identifying natural enemies of pathogenic bacteria Plants and animals produce substances known as antimicrobial peptides as a defense against intruding pathogens. The usability of antimicrobial peptides in human medicine is being evaluated, as are the applicability of what is known as bacteriophage therapy. Bacteriophages are viruses that infect bacteria, which potentially could be utilized for therapeutic purposes.

45 New business models addressing antibiotic resistance De-linkage means introducing mechanisms that separate the sales from the profits: Reimbursement for companies that are engaging R&D in antibiotics Providing prizes to the successful projects sharing risk among different stakeholders The second aspect is Private-public partnership Necessity to increase sharing of R&D efforts between differing organisations-- both private, small or large companies, but also public entities, such as universities or agencies and governments. New private-public partnerships are to be explored The third and last aspect is the necessity to adopt a systemic approach to the antibiotic resistance problem

46 ANTIBIOTIC AND RESISTANCE The unknown

47 Questions to be addressed: Is it possible to identify the countries that suffer the most from antibiotic resistance? Which countries lack surveillance data? Is it only LMICs or are there wealthy nations as well? What is the economic burden of antibiotic resistance? What is the magnitude and importance of transmission from animals to humans for the increasing resistance rates observed in human pathogens? What is the magnitude and impact of international travel? Who is responsible?

48 Dear colleague, As a pharmacist, do you find yourself a keyplayer in managing antibiotic resistance? Do you think that you can make a difference?

49 TAKE HOME MESSAGE Antibiotic resistance is a complex, global, multifactorial issue The burden of antibiotic resistance is unknown Awareness, communication, education, prevention surveillance, private-public partnership, and focused research are key factors Academia, civils societies, pharmaceutical industry, healthcare providers, and government need to collaborate together in order to tackle antibiotic resistance

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