1. Prevention, Surveillance and Statistics of Resistance to Antibiotics
Salma B. Galal, M.D. Ph.D.
Prof. Public Health and Medical Sociology
Former WHO technical officer
Egypt
World Congress of Microbes 2012, Guangzhou, China
Title:
This is a brief overview on antimicrobial resistance (AMR)

2. Purpose of this presentation
to give an overview on the antimicrobial resistance
to present suggested policies and strategies
Purpose:

3. Background to this presentation SG
Antimicrobial resistance (AMR) is the “resistance of a microorganism to an antimicrobial medicine to which it was previously sensitive. Standard treatments become ineffective and infections persist and may spread to others.”(WHO, 2012)
Since the 40s, antimicrobial resistance (AMR) has been spreading in number - type geographically
It leads to prolonged morbidity, risk of death and higher cost
AMR might set us back to the pre-antibiotic era
Background: Antimicrobial resistance (AMR) is a worldwide problem arising from the use of antibiotics in people, animals and plants. The survival of resistant strains can spread from an individual to the community. AMR began with the invention of antibiotics in the 1940s.
If antimicrobial resistance persists it can set us back to the pre-antibiotic era.
This presentation will describe the extent of the problem in different countries, the contributing factors to AMR and the action taken.
Which strategies and policies would decrease and slow down AMR?

4. Usually, a bacterium can get genetic elements from another resistant bacterium and become resistant itself (horizontal gene transfer), not only through genetic mutation.
(WHO Europe, 2011)

5. ANTIBIOTIC DISCOVERY AND RESISTANCE DEVELOPMENT
Discovered
Introduced
Resistance
into clinical use identified
Penicillin
1940
1943
(Methicillin 1965)
Streptomycin
1944
1947
1947,1956
Tetracycline
1948
1952
1956
Erythromycin
1955
Vancomycin
1972
1987
Gentamycin
1963
1967
1970
The table shows the discovery dates of different antibiotics and the dates of resistance development.
Source: CIBA Foundation (14). Reproduced with the permission according to Stuart B Levy

6. Presentation Outline Policies and Strategies Factors and Actions
Situation
Roadmap:

7. Drug-resistant organisms include viruses, bacteria, fungii and parasites
Drug resistant organisms cause:-
serious hospital infections (staphylococci, enterococci, gram-negative bacilli, clostridium difficile)
pneumonia and tuberculosis, sexually transmitted diseases (some strains of HIV, Neisseria gonorrhea, Candida)
food-borne diseases (Salmonella, Campylobacter)
parasitic manifestations (Plasmodium falciparum)
Drug-resistant organisms include all major agents causing diseases such as viruses, bacteria, fungi and parasites.
Bacteria such as staphylococci, enterococci, gram-negative bacilli, clostridium difficile cause serious hospital infections. Methicillin-resistant Staphylococcus Aureus (MRSA) causes serious hospital infections around the world.
Respiratory diseases such as pneumonia and tuberculosis
Food borne pathogens such as salmonella, camphylobacter
Sexually transmitted organisms such as some strains of HIV, neisseria gonorrhoeae, candida and other fungi
Parasitic manifestations such as plasmodium falciparium

8. Methicillin-Resistant Staphylococcus Aureus spread
Antimicrobials are misused / overused. E.g. methicillin-resistant Staphylococcus aureus (MRSA) spread
from health facilities
to communities and
other countries
According to the CDC, Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of staph bacteria that is resistant to beta-lactams antibiotics such as methicillin, oxacillin, penicillin and amoxicillin (since the 60s).
MRSA causes life-threatening severe hospital infections such as pneumonia, blood stream and surgical site infections. In the USA in 2000, over 50% of the S. aureus nosocomial infections were methicillin-resistant.
Vancomycin-resistant enterococci were documented in 1986 and are endemic to many US hospitals.
MRSA spread from hospitals to the community in persons who were not hospitalized. In the community, MRSA is mostly skin infections (see pictures on the CDC site).

9. In South America, hospital-isolated staphylococcus were found to be methicillin-resistant over 50% of the time in Bolivia, Peru and between 26-50% in Argentina, Venezuela, Paraguay, Uruguay and Ecuador.

10. Methicillin-resistant Staphylococcus aureus (MRSA)
In USA (2005), from hospitalized staph aureus infections 58% were MRSA ,000 persons had life-threatening infections and nearly 19,000 deaths resulted from MRSA, accounting for more deaths than AIDS, etc.(CDC)
SENTRY program in South East Asia showed MRSA prevalence rate of 23.8%, 27.8%, and 5% from Australia, China, and the Philippines
The prevalence in Africa ranged from 5%-45% (Bustamante,2011)
Over 22 countries participated in the SENTRY Antimicrobial Surveillance Program, which started in 1997 to monitor the pathogens and antimicrobial resistance for both nosocomial and community-acquired infections. “The major objectives include blood stream infections, community-acquired respiratory tract infections (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis), pneumonias in hospitalised patients, skin and soft tissue infections, and urinary tract isolates from hospitalised patients” (Commun Dis Intell 2003;27 Suppl:S61-S66).

11. Methicillin-resistant Staphylococcus aureus (MRSA) declined in USA (CDC)
Due to strict hospital infection control* measures
in hospitals MRSA declined 28% from 2005 to 2008 (MRSA Statistics)
MRSA bloodstream infections in hospitalized patients fell ~ 50% from 1997 to 2007 (National Healthcare safety Network)
17% drop of community onset MRSA infections
*The Interagency Task Force on Antimicrobial Resistance in the USA was initiated in 1999 to coordinate the activities of federal agencies regarding antimicrobial resistance. It includes
the Centers for Disease Control and Prevention (CDC)
the Food and Drug Administration (FDA)
the National Institutes of Health (NIH)
the Agency for Healthcare Research and Quality (AHRQ)
the Centers for Medicare and Medicaid Services (CMS)
the Department of Agriculture (USDA)
the Department of Defense (DoD)
the Department of Veterans Affairs (VA)
the Environmental Protection Agency (EPA)
the Health Resources and Services Administration (HRSA)
the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (HHS/ASPR)
In 2001 they developed A Public Health Action Plan to Combat Antimicrobial Resistance. The last report was in 2011.

12. Multidrug-resistant Tuberculosis (MDR – TB)
According to WHO (2011), about new cases of multidrug-resistant tuberculosis appear yearly, causing at least deaths.
Extensively drug-resistant tuberculosis (XDR-TB) has been reported in 64 countries
WHO estimates that 30% of the world’s population is infected with the tuberculosis bacterium
Multidrug-resistant TB (MDR-TB) is caused by organisms that are resistant to isoniazid and rifampicin. MDR-TB results from either infection with organisms which are already drug-resistant or become resistant during therapy.
Extensively drug-resistant TB (XDR-TB) is a form of TB caused by organisms that are resistant to isoniazid and rifampicin or any of the second-line anti-TB injectable drugs amikacin, kanamycin or capreomycin.

13. Parts of Russia and Kazakhstan have the highest percentage of Multidrug Resistant – TB in 1994 to 2011, followed by China.
The highest numbers of notified cases of MDR-TB in 2011 were reported not only in Russia and Kazakhstan but also in China, India, South Africa, Chile and others. In some countries in Africa and Asia laboratories are not well equipped.

14. John Conly, former Chairman of the Board for the Canadian Committee on Antibiotic Resistance (2010)
NDM1 (New Delhi metallo-β-lactamase-1) superbug is an enzyme that confers resistance to one of the most potent classes of antibiotics, known as carbapenems
10% of these NDM1-containing strains appear to be pan-resistant,
It is governed by a set of genes that can move easily from one bacterium to another
NDM1 is found in E.coli infecting kidney and bladder
Treated with colistin, this antibiotic causes toxic effects to the kidney in a third of the population
Superbugs are a microbial threat for hospitals that cause outbreaks and deaths. The extent of the damage they cause can be limited through infection controls in hospitals.
Some antibiotic resistant superbugs can spread through food – e.g. chicken given antibiotics - and water.
Surveillance is necessary.

15. In Europe
In EU, more than people die each year from infections caused by antibiotic resistant bacteria (WHO Europe, 2011)
Resistance is increasing in Europe for Gram-negative bacteria such as Escherichia coli or Klebsiella pneumoniae, where new resistant mechanisms are emerging and new drugs are not in sight. SG
Gram-negative bacilli produce enzymes that destroy last generation antibiotics, such as Escherichia coli and Klebsiella pneumonia (enteric organism), emerged and spread rapidly throughout many countries.
E. coli – an ordinary human pathogen - causes common infections such as urinary tract infection (WHO, fact sheet 194).
E. coli reached rates of 70% in some Southeast Asian countries and China and nearly 10% in some industrialized countries and USA. Some strains of E. coli are resistant to six drug classes.

16. Food-borne induced microbial resistance
Antibiotics are used (WHO Europe, 2011)
to treat food animals
to prevent them from developing diseases
to promote their growth
it promotes the development of antibiotic-resistant Salmonella* and Campylobacter and resistance genes that can be passed on to people
*multiresistant Salmonella Typhimurium definitive phage type (DT)104 that exhibits quinolone resistance
In England with the antibiotic’s use in poultry 1957–1960, tetracycline-resistant E. coli increased from 3.5% to 63.2%.
Fluoroquinolones used in food animals lead to antibiotic resistance in Salmonella and Campylobacter species causing food-borne infections in people.
Antibiotic resistance in Salmonella is associated with longer hospitalization and illness, a higher risk of invasive infection and a twofold increase in the risk of death for at least two years.

17. Animals, fish and people can transfer bacteria with resistant genes
Animals, fish and people can transfer bacteria with resistant genes. The transfer takes place in kitchens, barns and water sources.
Meat, poultry, fish, eggs, cheese and vegetables can contain antibiotic-resistant bacteria.
(WHO Europe, 2011)

18. Exposure to antibiotics is high in animals – during most of their lifespan - especially in countries, where antibiotic growth promoters (AGP) are used.
In Scandinavian countries, where policies are restricting antibiotic use, antibiotic usage in food animal production is more limited than in other countries such as the Netherlands and France.
(WHO Europe, 2011)

19. Resistance to chloroquine and sulfadoxine-pyrimethamine (WHO)
Resistance to chloroquine and sulfadoxine-pyrimethamine is in most malaria-endemic countries
1947, chloroquine was used for the prophylactic treatment of malaria (wiki)
1950s, P. falciparum resistant strains appeared in East / West Africa, South East Asia, and South America
resistant to artemisinins are emerging in South-East Asia (WHO)
Chloroquine is used as anti-rheumatic, anti-viral (HIV1) and anti-tumor which might widen the spread of resistance (Krafts et al, 2012)
Resistance to chloroquine, is widespread in 80% of the 92 countries where malaria continues to be a killer. The control of malaria has become difficult and has lead to the re-emergence of malaria in Africa and Asia.
Also the resistance to newer anti-malarial drugs is widespread and growing.
To contain the spread of malaria it is necessary to continuously supply new, effective and affordable drugs.

20. Sub-Sahara Africa, Asia with the exception of Russia and the northern countries of South America are chloroquine resistant.
In addition, some of the countries, such as Colombia, Venezuela and North Brazil in South America, West Africa and Burma in Asia, are also mefloquine resistant.
chemistdirect.co.uk

21. Presentation Outline Policies and Strategies Factors and Actions
Situation
Roadmap:
Use it to introduce each section.
Highlight the section you are about to present. Also announce the main sub-topics covered in the section.
The messages covered in this section are mostly factual statements (topics) if you are using an indirect approach.

22. Factors contributing to AMR (WHO, 2012)
National commitment and coordination is deficient,
Communities are insufficiently engaged
Surveillance and monitoring is weak / absent
inadequate systems to ensure quality and uninterrupted supply of medicines
In many developing countries following factors contribute to the problem:
Unnecessary and over prescription of antibiotics by the medical team,
overuse by patients and unawareness of drawbacks
over-the-counter selling without prescription

23. Factors contributing to AMR (continued)
The use of medicines is inappropriate, also in animal husbandry
infection prevention and control is poor
research and development of new diagnostics medicines / vaccines is insufficient

24. Interagency cooperation for food-borne resistance
Since 2005, World Health Organization (WHO), Food and Agricultural Organization (FAO) and the World Organization for Animal Health (OIE) work on food-borne resistance
to assess the public health risk associated with the usage of antibiotics in animal husbandry (including aquaculture)
to propose high-level management options to address the risks identified
The following strategies and guidelines were developed by the WHO, FAO and OIE:
WHO Global Strategy for Containment of Antimicrobial Resistance
WHO, Global Principles for the Containment of Antimicrobial Resistance in Animals Intended for Food
World Organization for Animal Health (OIE) developed guidelines on the prudent use of antibiotics in food animals

25. WHO Surveillance Effort SG
In 2008, WHO established the Advisory Group on Integrated Surveillance of Antimicrobial Resistance to support its effort to minimize the adverse effect on public health of antibiotic resistance associated with antibiotic usage in food animals (WHO Europe, 2011)
Antimicrobial resistance surveillance guidelines
Surveillance of resistance
Developed Software for surveillance resistance
The WHO Collaborating Centre for Surveillance of Antimicrobial Resistance developed WHONET in It is a free Windows-based database software for the management and analysis of microbiology laboratory data with a special focus on the analysis of antimicrobial susceptibility test results. WHONET is at the Brigham and Women's Hospital in Boston, and is used by clinical, public health, veterinary and food laboratories in over 90 countries to support local and national surveillance programs (AMR WHONET)-

26. Surveillance on 52 communicable diseases in EU countries
coordinated by the European Centre for Disease Prevention and Control, collects annual data on infections with resistant bacteria such as:
Streptococcus pneumoniae
Staphylococcus aureus
Escherichia coli
Enterococcus faecalis
Enterococcus faecium
Klebsiella pneumoniae
Pseudomonas auruginosa
Clostridium difficile
The activities of the European Centre for Disease Prevention and Control encompass:
Disease programmes
Surveillance
Scientific advice
Epidemic intelligence
Preparedness and response
Training
Health communication
Public health microbiology program
Annual reports are submitted.

27. Surveillance in USA on additional 11 other AMR
Acinetobacter baumannii
Mycobacterium tuberculosis
Neisseria gonorrhoeae and meningitidis
HIV
Plasmodium falciparum
Haemophilus influenzae
Helicobacter pylori
Trichomonas vaginalis
See slide 11 on Interagency Task Force on Antimicrobial Resistance in USA

28. Presentation Outline Policies and Strategies Factors and Actions
Situation
Roadmap:
Use it to introduce each section.
Highlight the section you are about to present. Also announce the main sub-topics covered in the section.
The messages covered in this section are mostly factual statements (topics) if you are using an indirect approach.

29. Global and National Coordination is necessary
Antibiotic resistance data are not available in all countries and often in some hospitals only
Standardization of data and indicators is necessary to work on globally and nationally
On national level in developing countries:-
Education of physicians and other health care providers for rational use of antibiotics and early detection
regulation of over-the-counter selling of antibiotics
Raising awareness of the community and population is also important.
The WHO Regional Office of South East Asia developed an information booklet for the public on Seasonal Communicable Diseases and Prevention of Antibiotic Diseases
Additionally, the Alliance for the Prudent Use of Antibiotics produces educational brochures for the public and for health professionals.
Antibacterial in the form of disinfectants and antiseptics in hospitals and households can kill susceptible bacteria and promote the growth of resistant strains.

30. Reducing the incidence of nosocomial infections in hospital and healthcare (AAM)
■ Hand hygiene
■ Isolation of infectious patients
■ Hospitals have to report infection rates to resistance mechanisms and to antibiotics used
■ Withholding reimbursement for treating nosocomial infections
■ Mandating the use of checklists for specific procedures to target transmission of pathogens from one patient to another
■ In developing countries:- access to basic healthcare equipment and resources (safe water)
The availability of an Infection Control Unit in hospitals is not sufficient, regular supervision and access to equipment is also important.
Rapid screening techniques are needed in hospitals for testing antibiotic resistance.
In addition to safe water, failure to manage hospital and human waste might jeopardize all the measures undertaken.

31. The World Health Organization’s policy package to combat antimicrobial resistance (Emily Leung et al, 2011)
• Commit to a comprehensive, financed national plan with accountability and civil society engagement
Strengthen surveillance and laboratory capacity
• Ensure uninterrupted access to essential medicines of assured quality
Civil societies reach the communities better than health services.
Prerequisites to commit to the national plan against antimicrobial resistance are:
The establishment of a national inter-sectoral steering committee with several stakeholders
The need to increase laboratory capacity to ensure reliable and rapid test results on which to base prescribing decisions and measures for the prevention and control of infections
A national body is necessary to develop the essential medicines list based on standard treatment guidelines.

32. WHO policies (continued)
Regulate and promote rational use of medicines, including in animal husbandry, and ensure proper patient care
Enhance infection prevention and control
Foster innovations and research and development for new tools
no action today, no cure tomorrow
7.April world day of AMR SG
The promotion of national standard treatment guidelines calls for proper training and supervision of health personnel and for mechanisms to make diagnostic support available
A proper organizational structure for developing and managing such policies and practices
Improving current diagnostic tests and antimicrobials and designing incentives to engage the industry in the development of new tools

33. USA Interagency Task Force on Antimicrobial Resistance (Interagency Task Force on Antimicrobial Resistance , USA,2010)
1. Surveillance
Goal 1: Improve the detection, monitoring, and characterization of drug-resistant infections in humans and animals.
Goal 2: Better define, characterize, and measure the impact of antimicrobial drug use in humans and animals in the United States. SG

34. 2.Prevention and Control
Goal 3: Develop, implement, and evaluate strategies to prevent the emergence, transmission, and persistence of drug-resistant microorganisms.
Goal 4: Develop, implement, and evaluate strategies to improve appropriate antimicrobial use SG

35. 3. Research
Goal 5: Facilitate basic research on antimicrobial resistance.
Goal 6: Practical applications of findings for the prevention, diagnosis and treatment of resistant infections.
Goal 7: Facilitate clinical research to improve the treatment and prevention of antimicrobial drug resistant infections.
 Goal 8: Conduct and support epidemiological studies to identify key drivers of the emergence and spread of AR in various populations SG

36. 4. Product Development
Goal 9: Provide information on the status of antibacterial drug product development and clarify recommended clinical trial designs for antibacterial products.
Goal 10: Consider opportunities for international harmonization and means to update susceptibility testing information for human and animal use.
Goal 11: Encourage development of rapid diagnostic tests and vaccines. SG

37. Next steps
Surveillance in hospitals for early detection of antibiotic resistance
Report to central authorities
Networking of information
Centrally controlled actions and measures
standardized nomenclature and laboratory procedures
Propose an agenda for the discussion. Be specific and precise as to what you want to achieve.
It focuses the discussion and directs the audience towards your objectives in making the presentation.
Close the presentation with something tangible and oriented towards the future.
Final note…
The storyboard approach allows you to shorten the presentation at the very last moment.
For example:
If you have about 10 seconds, present the first visual with the key message.
If you have about one minute, present the key message and the summary of the three sections (slide 19 of this document).
If you have about five minutes, present the key message, the summary of the three sections and add a few key visuals from each section to support your conclusions. SG

38. References
American Academy of Microbiology (AAM), Antibiotic Resistance: An Ecological Perspective on an Old Problem, 2009
Interagency Task Force on Antimicrobial Resistance, co-chairs Centers for Disease Control and Prevention, Food and Drug Administration, National Institutes of Health & others, A public health action plan to combat antimicrobial resistance, 2011& 2007
Emily Leung et al, The WHO policy package to combat antimicrobial resistance, Bull World Health Organ 2011;89:390–392 | doi: /BLT
WHO Regional Office Europe, Tackling antibiotic resistance from a food safety perspective in Europe, 2011
Stuart B Levy, Introduction, WHO Antibiotic Resistance synthesis of recommendations by expert policy group, 2001
See also references mentioned in slides / comments