Antibiotic Resistance and Medicinal Drug Policy

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Antibiotic Resistance and Medicinal Drug Policy

• Dr. Ken HarveySchool of Public Health, La Trobe
  University,
• Melbourne, Australia

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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 countrys response the quality use of
  medicines pillar of Australian drug policy
• The current challenge using information
  technology to further improve antibiotic use

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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.
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The start of antibiotic resistance Penicillin
Florey Chain1940
Fleming1928
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History of resistance
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Bacterial evolution vs mankinds 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

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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/arinf
  obank/

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Resistance Australia 2000

• Hospitals
• vancomycin-resistant enterococci (VREs)
• 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 15R)

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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.

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The consequences of antibiotic resistance

• Increased morbidity mortality
• best-guess therapy may fail with the patients
  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

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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 US1 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.

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Social factors 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.

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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)

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Antibiotic stewardship Australia
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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

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Drug audit, and change strategies
Compare drug use with Guidelines recommendations
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First Australian drug audits1978-82

• 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

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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 the failure of 3
  separate swabs to produce any growth on culture.
  Culture of the fourth swab grew
  methicillin-resistant Staphylococcus aureus.

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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

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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

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Audit results
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Audits results
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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

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Australian therapeutic guidelines Today
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Dr. Harveys visit to China was sponsored by

• The World Health Organization
• and hosted by Professor Yong-Hong Yang
• Beijing Childrens Hospital
• Professor Li Dakui
• Peking Union Medical College

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