1. Principles of Antibiotic Policies

2. Learning objectives
Explain how antibiotic use can select resistant strains of bacteria 
Identify important mechanisms used by antibiotic stewardship programmes to decrease bacterial resistance in hospitals
Describe the roles of the microbiology laboratory and IP&C staff in the containment of bacterial resistance in healthcare
 Participate in the formation of an antibiotic stewardship programme
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3. Time involved
45 – 60 minutes
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4. Introduction
Discovery of antibiotics – revolutionary event that saved millions of lives
Emergence of resistance – reduced effectiveness, increased toxicity, increased costs
To preserve susceptibility – or to postpone development of resistance – antibiotics should be used rationally
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The emergence of resistance to antibiotics has created a vicious cycle, requiring new antibiotics that are always more expensive and often more toxic – leading to more resistance. Because of the high price leading to non-availability in countries with restricted resources – and at the end, leading to a pre-antibiotic era for many patients. Rational use of antibiotics is therefore of prime interest to everyone: government, physicians, patients and the public.

5. Antibiotics Fleming changed the course of history
Mould contaminated an experiment – contained penicillin
Killed the Staphylococcus aureus that had been growing in the dish
Penicillin altered the treatment of bacterial infections
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Dr Alexander Fleming
Dr Alexander Fleming was a microbiologist who discovered the action of penicillium mold on staphylococci cultured in a Petri dish – this was the discovery of penicillin and the start of the antibiotic era.
In 1928, Fleming made a chance discovery from an already discarded, contaminated Petri dish. The mould that had contaminated the experiment turned out to contain a powerful antibiotic, penicillin. However, though Fleming was credited with the discovery, it was over a decade before someone else turned penicillin into the miracle drug for the 20th century.

6. Antibiotic Resistance
Antibiotic resistance develops
Through natural mutations of bacterial genes
Through transfer of resistance genes between different bacteria via plasmids, transposons, etc.
If a bacterial population with newly resistant bacteria are exposed to a specific antibiotic, they will be selected and develop a new resistant strain
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Antibiotics are not mutagenic agents, so they do not cause development of resistance. Development of resistance is a natural phenomenon of bacterial variability. Bacteria have another mechanism to acquire resistance genes; that is horizontal gene transfer between often very different bacteria. This horizontal gene transfer is especially important because this process can allow rapid spreading of some resistance genes.
European Antimicrobial Resistance Surveillance Network (EARS-Net)  - The results of the EARS-Net  are available from the interactive database that provides information on the occurrence and spread of antimicrobial resistance in Europe. See
USA information may be found at National Healthcare Safety Network (NHSN). Data during , Infect Control Hosp Epidemilol Jan; 34(1):1-14. doi: / Epub 2012 Nov

7. Mechanisms of resistance
Resistance can be mediated by:
Change in antibiotic target site - altered penicillin binding proteins, altered DNA gyrase:
Beta-lactams, Quinolones
Production of detoxifying enzymes:
Beta-lactams (Beta-lactamases) , Aminoglycosides, Chloramphenicol
Decreased uptake(reduced permeability, active efflux):
Erythromycin, Tetracyclines, Beta- lactams
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Different bacteria have various mechanisms of resistance towards different antibiotics. It is important to note is that if we are treating one patient's infection, we are acting on his/her infectious agent, and at the same time on his/her entire normal flora.
In the normal flora of an individual patient, we can then select some resistant mutant and this resistant normal flora member can then transfer that particular resistance to pathogenic bacteria. Furthermore, as bacterial flora is exchanged between people, we theoretically (sometimes also practically) act on the whole world’s bacterial flora while treating one patient.

8. Antibiotic use outside human medicine
Antibiotics are used as treatment of infections
In veterinary medicine
In agriculture
Antibiotics are also used as growth promotors
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It is important to limit the use of antibiotics as growth promotors. In addition, it is also important to use antibiotics prudently in veterinary medicine and agriculture and thus decrease the general use of antibiotics.

9. Clinical Impact of Resistance
Increased morbidity
Increased mortality
Extended hospital stay
Increased admission to intensive care
Loss of bed days
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The clinical impact of resistance is huge. For example, the impact of resistance in the community, especially Mycobacterium tuberculosis resistance, has hampered treatment of tuberculosis in many patients, especially in immunocompromised ones such as AIDS patients in developing countries.

10. Types of antibiotic uses
Empirical therapy
Without the knowledge of pathogen
Pathogen-directed therapy
Knowing the pathogen and susceptibility to antibiotics
Prophylaxis
Surgical
Medical
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Empirical therapy is the treatment of an infection without knowledge of the pathogen. It is very often used in severe infections before culture and sensitivity data are known or if there is no available microbiology laboratory.
Pathogen-directed therapy is an ideal method. The treatment is guided by sensitivity data of the involved pathogen.
The prophylactic use of antibiotics is very well defined as 1) surgical prophylaxis and 2) medical prophylaxis. Medical prophylaxis is used for prevention of specific infections in severely immunocompromised patients and in contacts of known infected cases (e.g., tuberculosis or meningococcal meningitis). Unfortunately, the prophylactic use of antibiotics is very often inappropriate.

11. Dealing with resistance
Antibiotic stewardship
Surveillance
Antibiotic policies
& guidelines
Antibiotic management
programmes
Prevention of spread
Infection prevention & control in
healthcare settings
Isolation
Hand Hygiene
Environmental hygiene
Reduction
Usage control
Appropriate use
Human
Animal
Environmental
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To postpone development of resistance, we have to prevent spread of resistant bacterial strains in health care facilities and reduce usage of antibiotics. To reduce antibiotic usage, we have to introduce antibiotic stewardship.
We can also consider vaccination in community settings – e.g. vaccination against pneumococci.

12. Antibiotic stewardship programmes - 1
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Can modify prescribing practices
Should lead to reduced, rational use
Should be well designed, and implemented
Should be based on education
Ideally should be a mixture of measures that are:
Voluntary
Persuasive
Restrictive
Antibiotic stewardship programmes are powerful tools in reducing resistance. These programmes should be based on education and be a mixture of voluntary, persuasive, and restrictive measures. Every physician is convinced that he/she can prescribe any medicine because of his/her education. This will not be possible if there is a working antibiotic stewardship programme.

13. Antibiotic stewardship programmes - 2
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Key to modifying prescribing practices, stewardship programmes must include:
National policies
Local hospital or health care policies
Formularies and guidelines
Education
Effective microbiology laboratory support
Audits
Effective working relationship with IP&C* teams
*IP&C: Infection Prevention and Control

14. Key Elements of National Antibiotic Policies
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Legislation required to regulate production and import
Legislation to impose limitation of use in veterinary practices to treatment only
Not as growth promoters
Legislation to reduce over the counter use
Education of the general population
Reduce expectations
Avoid misuse and over demand
National policy should include education of medical personnel both at graduate and postgraduate levels. Government should ensure that all essential antibiotics are present in sufficient quantities; that all healthcare facilities have access to a microbiology laboratory; and that professional societies develop guidelines for treatment of community-acquired infections. One very important regulation is that only medical doctors or other appropriately trained healthcare workers can prescribe antibiotics.

15. Hospital stewardship programmes
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Important elements of an effective hospital programme:
Antibiotic Committee
Antibiotic Management team
Formularies, guidelines and protocols
Education
Audits
Careful management of antibiotics in hospitals requires a holistic approach, including involvement of hospital administration and other stakeholders, as well as dedicating sufficient manpower and financial resources.

16. Antibiotic Committee
Can be a “stand alone” Committee, or part of Drugs and Therapeutics Committee
Membership should include:
Physicians and nurses who prescribe antibiotics
Pharmacists
Microbiologists
Members of Management/Administration
Members of Infection Control Committee
Others, as needed
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All physicians that prescribe antibiotics should have a representative on the Antibiotic Committee. Nurses should be included if they prescribe antibiotics. Pharmacists can be a consultant for prescribing information, as well as a microbiologist who will also provide data about local resistance patterns. A member of the management/administration is essential; without management antibiotic stewardship programmes will not be effective. An IP&C Committee member can provide data on spread of resistant strains of pathogens.

17. Antibiotic Management Team
Team to advise on antibiotic use, audit of prescribing, introduction of new antibiotics
Larger hospitals: can include infectious disease (ID) physicians, clinical pharmacologists, pharmacists, clinical microbiologists, any doctor authorised to use reserve list
Smaller institutions: minimum requirement: antibiotic pharmacist (at least part-time), with support from ID or IP&C physician
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Not all countries have clinical pharmacologists, however this specialist profile is ideal if it exists. If not, a pharmacist with specialist training would be a very good member of the team.

18. Guidelines and Protocols
Should include:
Protocols for the evaluation of parenteral antibiotics
Include stop orders after 3-5 days and recommendations for sequential treatment
Protocol for list of reserve antibiotics
How to order
Who can authorise
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Antibiotics for a local formulary should include antibiotics from the WHO list of essential antibiotics, and other antibiotics according to local/regional/national policies and resistance patterns. If there is no microbiology laboratory, use regional or national or, in the worse case, international resistance data to provide guidance.

19. Hospital Guidelines/Policies
Local hospital or health care policies should focus on using antibiotics that:
Have narrowest possible spectrum
Are inexpensive
Have minimal toxicity
Have least impact on development of resistance
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20. Hospital formularies and protocols
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Antibiotic formularies: no drug outside those listed should be used
Protocols for empiric and targeted treatment of common infections
Protocols for surgical prophylaxis
Protocols for de-escalation of parenteral use
Protocols for use of a reserve list
It is very important to raise awareness of physicians that when they treat patients with infections, they are actually acting against pathogens. Most physicians do not deal with infections very often, so they may not know the details of which antibiotic is best against a particular pathogen or is not effective against normal flora, or is the least prone to select resistant strains. These issues are typically the specialist knowledge of infectious disease physicians, clinical microbiologist s or any physician (e.g., ICU physicians) who is specifically interested in the treatment of infection. For all other physicians, it is important to follow guidelines and protocols. Formularies and protocols should be developed after broad discussion among all clinicians and take into consideration their views on types of antibiotics, routes of administration, dosing, and duration of therapy.

21. Education programmes - 1
Should include:
Formal meetings
Clinical rounds with antibiotic management team/committee members
Formal lectures
Focus on:
New antibiotics
New methods of administration
Influence on bacterial ecology
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Education about prudent use of antibiotics should be provided regularly, especially, but not only, for younger physicians. The best education method is during clinical rounds, however this type of education is not systematic; therefore it has to be supplemented by formal meetings and lectures (especially for new antibiotics and methods of administration). Regular feedback of antibiotic usage and resistance patterns (if available) is very important.

22. Education programmes - 2
Should be provided by Senior member of Antibiotic Team, or independent expert
Should not be provided by individuals from pharmaceutical companies, unless a committee or antibiotic team member is present
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Drug company presentations have to be endorsed by the Antibiotic Committee in advance.

23. Stewardship: Role of the Microbiology Laboratory
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Regular reporting of changing resistance patterns
Newsletters
Specialty-specific data
Restricted antibiotic reporting
Routinely only first line antibiotics
Reserve antibiotics only if pathogen is resistant to first line antibiotics
Patient specific data (culture & sensitivity) to optimise treatment
The microbiology laboratory plays a crucial role, not only in the treatment of individual patients by providing culture and sensitivity results, but also in designing of the formulary and developing specific protocols.

24. Stewardship: role of Clinical Microbiologist/ID Specialist
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Provide leadership to Antimicrobial Team
Antibiotic ward rounds
Interpretation of patient-specific data (culture & sensitivity) to optimise treatment
Active surveillance/ awareness
Screening for carriage of resistant organisms
Molecular detection and typing
Additional information from the microbiology laboratory includes surveillance of resistance data with regular feedback to prescribers. Screening of carriage of resistant pathogens is done according to IP&C policies and can be very useful in designing empiric treatment of patients in case of infection.

25. Audit: Monitoring compliance
1. Are antibiotics being used in accordance with approved protocols?
Empirical vs. targeted treatments clearly specified?
Stopped at the correct time?
Based on clinical needs and microbiology results?
Correct use of surgical prophylaxis guidelines?
Antibiotic
Timing
Dosage
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Audit questions can be developed with „YES” or „NO” answers. These are very simple to perform and unambiguous to interpret.

26. Audit: Monitoring effectiveness
2. Are our policies & guidelines being followed?
Consumption data: Based on stock controls
Signed prescriptions
Usage data
DDD*: based on patient bed days / length of stay
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Auditing antibiotic use is of utmost importance for the prudent use of antibiotics. It should always be performed with immediate feedback to the audited physicians. Auditing antibiotic use is a job for a physician (ID or microbiologist) as clinical notes have to be reviewed and interpreted correctly.
*DDD = defined daily dose

27. Audit: Monitoring Appropriateness
3. Are the policies being used effectively?
Dosage: too much- too little?
Timeliness: start-stop dates?
Appropriateness: compliant with local policies?
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The reason for giving an antibiotic to a patient should always be written in the physician notes. Local policy should be revised once a year according to the last year of resistance data.

28. Audit data Regular and timely feedback
Use as evidence for further teaching
Discuss in antibiotic ward rounds
Assess efficacy of guidelines and protocols before regular review
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Audit results should be presented in formal meetings with all physicians of the audited ward. In addition, they should be presented during clinical rounds; rounds serve as an excellent education method.

29. Control and Prevention of Healthcare-associated Infections
Work in close collaboration with Microbiology laboratory
Have early warning system, based on regular surveillance
Act promptly to detect and manage outbreaks
Have effective isolation policies
Ensure effective cleaning and high compliance with hand hygiene
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Resistant bacterial strains can be selected by use of antibiotics, however they may also enter the healthcare facility with an infected/colonised patient. Therefore the IP&C programme has to have measures to prevent spread of such imported strains (active screening, isolation), as well as spread of resistant strains selected in the facility. The microbiology laboratory is crucial in this task.
The IP&C programme also has to have measures in place to decrease all healthcare-associated infections, as decreased infections will result in decreased use of antibiotics and reduced opportunities for selection of resistance.

30. Further reading
WHO Global Strategy for containment of antimicrobial resistance WHO,
Dellit TH, et al. Infectious Disease Society of America and Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:
Richards J. Emergence and spread of multiresistant organisms: can infection control measures help? Int J Infect Control 2009;v5:i2 doi: /ijic.V5i
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31. Quiz
Methods to manage resistance are preventing spread of resistant pathogens, antibiotic stewardship, and reduction of antibiotic use. T/F
Additional information from the microbiology laboratory, useful in prudent use of antibiotics, is reporting sensitivity testing to broad spectrum antibiotics as a first line antibiotics. T/F
The topics usually included in antibiotic policies are:
List of antibiotics in the formulary- with the possibility to use some antibiotics outside the formulary.
Guidelines for empiric and targeted treatment not including dosage and duration of treatment.
Protocols for reserve antibiotics including how to order and who authorises its use.
Protocols for surgical prophylaxis including stop-orders after 48 hours.
All of the above.
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True e

32. International Federation of Infection Control
IFIC’s mission is to facilitate international networking in order to improve the prevention and control of healthcare associated infections worldwide. It is an umbrella organisation of societies and associations of healthcare professionals in infection control and related fields across the globe .
The goal of IFIC is to minimise the risk of infection within healthcare settings through development of a network of infection control organisations for communication, consensus building, education and sharing expertise.
For more information go to
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