Antibiotic Resistance&
prevention
Content
History of Antibiotic resistanceThe consequences of Antibiotic resistance
Reasons for Antibiotic resistance
Prevention
The start of antibiotic resistance: Penicillin
Fleming1928
Florey&
Chain1940
History of resistance
Antibiotic Discovered Introduced
into Clinical
Use
Resistance
Identified
Penicillin 1940 1943 1940
Streptomycin 1944 1947 1947
Tetracycline 1948 1952 1956
Erythromycin 1952 1955 1956
Vancomycin 1956 1972 1987
Gentamycin 1963 1967 1970
“There are two major effects of an antibiotic: therapeutically, it treats the invading infectious organism, but it also eliminates other, or non-disease producing, bacteria in its wake. The latter do, in fact, contribute to the diversity of the ecosystem and the natural balance between susceptible and resistant strains.…
“The consequence of antibiotic use is, therefore, the disruption of the natural microbial ecology. This alteration may be revealed in the emergence of types of bacteria which are very different from those previously found there, or drug resistant variants of the same ones that were already present.”
Levy, 1997
"... the mounting use of antibiotics, not only in people, but also in animals and in agriculture, has delivered a selection unprecedented in the history of evolution." Levy, 1997
DRUG RESISTANCE THREATENS TO REVERSE
MEDICAL PROGRESSCurable 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.
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
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.
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
Antibiotic Failures are NOT all due to
ResistanceLack of effectiveness in vivo may not be due to
bacterial resistance; the antibiotic may not be able to reach the microorganisms: cannot
go through blood brain barrier be too toxic at doses required to be effective against targeted microorganisms...
Sustained Antibiotic Use Contributes to Resistance
initial 3-month: use of AMI restricted, TOB & GEN unrestrictedthen 12 months when AMI was primary aminoglycoside
Muscato JJ1991. An evaluation of the susceptibility patterns of gram-negative organisms isolated in cancer centres with aminoglycoside usage. Journal of Antimicrobial Chemotherapy. 27 Suppl C:1-7.
3 month initial
12 month follow
usage % patient days Amikacin %pd 20.1 83.9 Tobramycin %pd 66.1 10.0 Gentamicin %pd 13.9 6.1 % resistance amikacin 0.85% 1.3% NS tobramycin 6.5% 2.6% P = 0.001 gentamicin 7.6% 4.8% P = 0.052
Antibiotics overuse creates ‘Superbugs’
50 million tons antibiotics per year
‘Superbugs’ resistant to most antibiotics
Example: Tuberculosis
2.5 million deaths
Mycobacterium tuberculosis
increasingly resistant
Resistance Seems to Develop Mostly in ICU
Resistance % in ICU /IP /OP
0 20 40 60 80 100
MRSE
MRSA
CFZRENT
IMIRP
VRE
% resistantICU IP OP
Project ICARE (Intensive Care Antibiotic Resistance Epidemiology) by CDC and Emory U SPH to collect data on 8 US hospitals:
For 8/10 pathogens considered, resistance was higher among in hospital isolates
How does animal use of antibiotics contribute to resistance?
Animals consume and excrete antibiotics (approximately 2 trillion lbs of manure generated in USA annually)
Animals can transmit resistant bacteria in food Food of animal origin most common cause of food-borne
infections due to: Salmonella Campylobacter Yersinia E Coli 0157,H7
Genetic transfer to human specific organisms (avoparcin in pigs and chickens). This can also occur with plant bacteria.
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.
Prevention
1-Vaccinate
Influenza vaccine
S.pneumoniae vaccine 7 vaccine serotypes are also most
resistant So vaccine reduces incidence of
infections due to the 7 serotypes and incidence of resistant strains
2- Diagnose & Treat Infection Effectively
Target the pathogenTarget empiric therapy to likely pathogensCulture the patientTarget definitive therapy to known pathogensOptimize timing, regimen, dose, route and durationMonitor response and adjust treatment when needed
3- Treat infection, not contamination
Blood cultures
Use proper antisepsis for blood cultures
Avoid culturing vascular catheter tips
Avoid culturing through temporary vascular catheters
4-Treat infection, not colonization
Treat pneumonia not the tracheal aspirate not endotracheal tube
Treat urinary tract infection not the indwelling catheter not simple bacteriuria
Treat bacteremia not the catheter tip or hub
Treat bone infection not the skin flora
5- Follow Established Guidelines
Consult Specialist
Follow Guidelines
6-Use Local Data
Know your antibiogram
Know your formulary
Know your patient population
7-Stop Antimicrobial Treatment
When infection is treated
When infection is not diagnosed
When infection is unlikely
8-Prevent Person to Person TransmissionHealth Care Facility: Use standard infection
control precautions Follow airborne, droplet
and contact precautions When in doubt, consult
infection control experts
Community Setting Stay home when you are
sick Keep your hands clean Set an example
9-Prevent Transmissionfrom Environment
Get the Catheters out Use catheters only when essential
Use the correct catheter
Use proper insertion and catheter-care protocols
Remove catheters when they are no longer essential
Follow disinfection protocols From stethoscopes
… to endoscopes
10- Use Hospital ControlsEducational & Persuasive Approaches:minor effect
Facilitative Strategies clinical specialist or pharmacy clinician to advise
computer help screens when ordering
Power Strategies Formulary Control
Monitor usage with time limits on prophylactic, empiric, therapeutic uses
Restriction of Drugs classified as: Uncontrolled: available for all physicians, Monitored: usage monitored thru system Restricted: ID specialist only
Hospital Control: Power
1-Formulary Control most common method
pharmacy and therapeutics
committee
selects ab in hospital formulary
based on the ab medical
usefulness, cost, relevance to
epidemiologic situation
no duplication
constant revision
Hospital Control: Monitor
2-Monitor and evaluate empiric, therapeutic &
prophylactic use
prescriptions include type of rx: E/T/P
Time limits
Empiric: 3 days
Prophylactic: 2 days
Therapeutic: 7 days
extension requires justification written by the
prescribing physician
requiring MD to justify prescriptions proper usage.
Hospital Control: Restrict
3-Restriction of Drugs classified
as: Uncontrolled: available for rx by
all physicians
Monitored: available but usage
monitored through system
Restricted: available only after
consultation with ID specialist or
limited list of MD
Hospital Control
4- Antimicrobial form forms consume time to be filled act as a deterrent for casual prescriptions information obtained on form used to monitor
proper usage
5- Laboratory reporting focus on formulary non formulary abS reported when multiple
resistance occurs reporting of abS prompt to allow rapid switching
to more appropriate and narrow spectrum ab
6- Concurrent control most beneficial to patient care, not retrospective easier implemented when rx thru computer
system
Thank you!