Antibiotic Resistance
and
Medicinal Drug Policy
Dr. Ken Harvey
School of Public Health, La Trobe University,
Melbourne, Australia
1
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
2
Press Release
WHO/41
12 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
The start of antibiotic
resistance: Penicillin
Fleming
1928
Florey
&
Chain
1940
4
History of resistance
1941
1943
1945
1950
1952
1956
Penicillin
Streptomycin
Cephalosporins
Tetracyclines
Eryrthromycin
Vancomycin
1960
1962
1962
1970
1980
2010
Methicillin
Lincomycin
Quinolones
Penems
Monobactams
The end of the
antibiotic era?
5
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
6
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/
7
Resistance:
Australia 2000
• Hospitals
– vancomycin-resistant enterococci (VRE’s)
– multi-resistant Staph. aureus (MRSA) NB. vancomycinresistant 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)
8
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 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
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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 nonresistant 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.
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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 microorganisms 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
15
Drug audit, and change
strategies
Compare drug
use with
Guidelines
recommendations
Identify
issues
Implement
change strategies
Develop
consensus approach
16
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
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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.
18
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
Patients receiving antibiotic therapy
40
30
20
10
0
1978
1982
percentage of patients receiving antibiotic therapy
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Audits results
Percentage of appropriate treatments
80
60
40
20
0
1978
medical wards
1982
surgical wards
total
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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. 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
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