Antibiotic Resistance and Medicinal Drug Policy

1. Antibiotic Resistance and Medicinal Drug Policy Dr. Ken HarveySchool of Public Health, La Trobe University, Melbourne, Australia 1

2. Lecture outline • Why the concern about antibiotic resistance? • The history, microbiological and social determinants of antibiotic resistance • Containing antibiotic resistance: microbiological surveillance, antibiotic utilization studies and other interventions • One country’s response: the quality use of medicines pillar of Australian drug policy • The current challenge – using information technology to further improve antibiotic use

3. Press Release WHO/4112 June 2000 DRUG RESISTANCE THREATENS TO REVERSE MEDICAL PROGRESS Curable diseases – from sore throats and ear infections to TB and malaria --are in danger of becoming incurable A new report warns that increasing drug resistance could rob the world of its opportunity to cure illnesses and stop epidemics. 3

4. The start of antibiotic resistance: Penicillin Florey& Chain1940 Fleming1928

5. History of resistance

6. Bacterial evolution vs mankind’s ingenuity • Adult humans contains 1014 cells, only 10% are human – the rest are bacteria • Antibiotic use promotes Darwinian selection of resistant bacterial species • Bacteria have efficient mechanisms of genetic transfer – this spreads resistance • Bacteria double every 20 minutes, humans every 30 years • Development of new antibiotics has slowed – resistant microorganisms are increasing

7. Surveillance of resistance: Australia Data are collected from 29 laboratories around Australia, including public hospital and private laboratories, in both metropolitan and country areas. Australia, like China, is a contributor to the WHO A-R Infobank: http://oms2.b3e.jussieu.fr/arinfobank/

8. Resistance: Australia 2000 • Hospitals • vancomycin-resistant enterococci (VRE’s) • multi-resistant Staph. aureus (MRSA) NB. vancomycin-resistant strains have been found in Japan and the USA but not yet in Australia • Community • Strep. Pneumoniae (Penicillins 15% I, 2% R; macrolides & tetracyclines 20% R) • Haemophilis influenzae (Penicillins 20% R ; macrolides & tetracyclines 10% R) • E. coli (amoxycillin 45% R ; amoxy-clav 10% R ; trimeth 15%R)

9. Resistance: The World 2000 • In much of South-East Asia, resistance to penicillin has been reported in up to 98% of gonorrhoea strains. • In Estonia, Latvia, and parts of Russia and China, over 10% of tuberculosis (TB) patients have strains resistant to the two most effective anti-TB drugs. • Thailand has completely lost the use three of the most common anti-malaria drugs because of resistance. • A small but growing number of patients are already showing primary resistance to AZT and other new therapies for HIV-infected persons.

10. The consequences of antibiotic resistance • Increased morbidity & mortality • “best-guess” therapy may fail with the patient’s condition deteriorating before susceptibility results are available • no antibiotics left to treat certain infections • Greater health care costs • more investigations • more expensive, toxic antimicrobials required • expensive barrier nursing, isolation, procedures, etc. • Therapy priced out of the reach of some third-world countries

11. Therapy priced out of the reach of the poor • A decade ago in New Delhi, India, typhoid could be cured by three inexpensive drugs. Now, these drugs are largely ineffective in the battle against this life-threatening disease. • Likewise, ten years ago, a shigella dysentery epidemic could easily be controlled with cotrimoxazole – a drug cheaply available in generic form. Today, nearly all shigella are non-responsive to the drug. • The cost of treating one person with multidrug-resistant TB is a hundred times greater than the cost of treating non-resistant cases. New York City needed to spend nearly US$1 billion to control an outbreak of multi-drug resistant TB in the early 1990s; a cost beyond the reach of most of the world's cities.

12. Socialfactors fuelling resistance • Poverty encourages the development of resistance through under use of drugs • Patients unable to afford the full course of the medicines • Sub-standard & counterfeit drugs lack potency • In wealthy countries, resistance is emerging for the opposite reason – the overuse of drugs. • Unnecessary demands for drugs by patients are often eagerly met by health services and stimulated by pharmaceutical promotion • Overuse of antimicrobials in food production is also contributing to increased drug resistance. Currently, 50% of all antibiotic production is used in animal husbandry and aquiculture • Globalization, increased travel and trade ensure that resistant strains quickly travel elsewhere. So does excessive promotion.

13. Postponing the end of the antibiotic era • Antibiotic stewardship (prudent use) • Contain the spread of resistant micro-organisms and relevant genes (infection control) • Develop new antibiotics that have novel modes of action or circumvent bacterial mechanisms of resistance (research)

14. Antibiotic stewardship: Australia

15. What are Antibiotic Guidelines? • Best practice recommendations concerning the treatment of choice for common clinical problems • Written by national experts • Evidence based where possible, peer-consensus where not • Regularly updated every 2 years • Endorsed by the Australian Medical Association, etc. • Used for medical education, problem look-up and drug audit

16. Identifyissues Implementchange strategies Developconsensus approach Drug audit, and change strategies Compare drug use with Guidelines recommendations

17. First Australian drug audits:1978-82 • The 700 bed Royal Melbourne Hospital was surveyed. The 240 bed sample comprised: • 3 general medical units • gastroenterology unit • haematology-oncology unit • 4 general surgical units • orthopaedic unit

18. Inappropriate prescribing • Example of a drug not required: • A patient with suspected infected burns received oral flucloxacillin and penicillin V. Therapy was continued for 23 days despite thefailure of 3 separate swabs to produce any growth on culture. Culture of the fourth swab grew methicillin-resistant Staphylococcus aureus.

19. Inappropriate prescribing Example of incorrect administration: Surgical antibiotic prophylaxis accounted for 100 prescriptions and, of these, 23 were given 2 to 12 hours AFTER the operation, a delay that largely nullified their value. Example of inadequate cover: A patient received gentamicin for peritonitis, thereby ignoring the anaerobic flora of the bowel. Metronidazole or clindamycin should have been added

20. Change strategies used • Feedback of audit results to prescribers followed by discussion at grand rounds and unit meetings • Use of Antibiotic Guidelines in undergraduate and postgraduate teaching • Rewriting the next edition of Antibiotic Guidelines, incorporating additional text to clarify misunderstandings and problems observed

21. Audit results

22. Audits results

23. Initial conclusions • Antibiotic prescribing improved • Surgeons (prophylaxis) were responsible for more inappropriate prescribing than physicians • Some persisting patterns of inappropriate antibiotic use appeared to reflect pharmaceutical company promotion • There was also a need for ongoing campaigns because hospital staff changed

24. Australian therapeutic guidelines: Today

25. Dr. Harvey’s visit to China was sponsored by The World Health Organization and hosted by Professor Yong-Hong Yang Beijing Children’s Hospital & Professor Li Dakui Peking Union Medical College 25