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!