Antibiotic Resistance

Dr. dr. M.SABIR,MS

Outline of presentation
Emergence of antimicrobial resistance
Evolution of antimicrobial resistance
Development of resistance
Mechanism resistance antibiotic in bacteria
Natural and acquired resistance
Key prevention strategies
 Antimicrobial
agent

Human host Microorganisms

The interaction between antimicrobial agents,

microorganism and human host can be viewed as a
triangle. Any effect on one side of the triangle will
have effects on the other two sides
 Penicillin, was discovered in 1929 by Sir Alexander Fleming
In 1939, Ernst Chain and Howard Florey developed a way to isolate
penicillin and used it to treat bacterial infections during the Second
World War
 Evolution of antimicrobial resistance
Penicillin Methicillin

S. aureus Penicillin-resistant Methicillin-resistant

[1950s] S. aureus [1970s] S. aureus (MRSA)

[1997] Vancomycin

[1990s]

Vancomycin Vancomycin Vancomycin-resistant

resistant iintermediate- enterococci (VRE)
S. aureus
resistant
S. aureus
 Rational Design of an antimicrobial
agent

Select an appropriate target

Identify a chemical lead (i.e. a new
molecule with inhibitory activity on the
target) Average
10 years
Modify the lead compound to enhance
potency
Evaluate in vitro activity
Evaluate in vivo activity and toxicity
Test in clinincal trials and develop
 DEVELOPMENT OF RESISTANCE (1)
Bacterial cells that have developed resistance are not killed off.
They continue to divide - Resulting in a completely resistant
population.
Mutation and evolutionary pressure cause a rapid increase in
resistance to antibiotics.
 DEVELOPMENT OF RESISTANCE (2)
Modern technology and sociology can further aggravate the
development of resistant strains.
Travelers carry resistant bacteria.
They travel with several or many other people.
Other people are infected with the resistant bacteria.
These people continue traveling and infecting.
The process is repeated and the resistant bacteria spread
 DEVELOPMENT OF RESISTANCE (3)

There are more large cities in the world today.

Large numbers of people in relatively small areas
Passing antibiotic-resistant pathogens is easier.
Many large urban populations have poor sanitation.
 DEVELOPMENT OF RESISTANCE (4)

Food is also a source of infection that could affect the

development of resistance.
More meals are prepared outside the home.
Contamination goes unnoticed until infection has started.
Outbreaks of Escherichia coli O157 in spinach and lettuce in the US.
As the number of foodborne infections increases, so does the use of
antibiotics.
Causes an increase in the development of resistance.
 DEVELOPMENT OF RESISTANCE (5)
An important social change is the increase in the number of
people who are immunocompromised.
Necessitates increased use of antibiotics
Fosters development of resistance

Emerging and re-emerging diseases are another source for

resistance.
Emerging diseases have not been seen before.
Re-emerging are caused by organisms resistant to treatment.
Mechanisms of antibiotic resistance in bacteria
 Antibiotic Method of Resistance
Chloramphenicol reduced uptake into cell
Tetracycline active efflux from the cell
-lactams, Erythromycin, eliminates or reduces
Lincomycin binding of antibiotic to cell
target
-lactams, enzymatic cleavage or
Aminoglycosides, modification to inactivate
Chloramphenicol antibiotic molecule
Sulfonamides, metabolic bypass of
Trimethoprim inhibited reaction
Sulfonamides, overproduction of
Trimethoprim antibiotic target (titration)
Mechanisms of resistance**
The target site may be altered
Access to the target site may be altered (altered uptake or
increased exit)
Altering entry, for example by decreasing the permeability of the
cell wall
Pumping the drug out of the cell (known as an efflux mechanism)
Enzymes that modify or destroy the antimicrobial agent may
be produced (drug inactivation)
Beta-lactamases
Aminoglycoside-modifying enzymes
Chloramphenicol acetyl transferases
Natural & acquired resistance
Natural resistance
Chromosomic genetic support
Affect almost all species strains
Existed before antibiotic use (Enterobacter sp. - amoxicillin)
Acquired resistance (mutation)
Chromosomic, plasmidic or transposon genetic support
Affects a fraction of strains
Increased with antibiotic use
(extended spectrum beta-lactamase producing E. coli)
Mechanisms of horizontal gene transfer (HGT) in bacteria
Horizontal gene transfer between bacteria

Transformation occurs when naked DNA is released on lysis of

an organism and is taken up by another organism
The antibiotic-resistance gene can be integrated into the
chromosome or plasmid of the recipient cell
Horizontal gene transfer between bacteria (2)

In transduction, antibiotic resistance genes are transferred from one

bacteria to another by means of bactheriophages and can be
integrated into the chromosome of the recipient cell (lysogeny)
Horizontal gene transfer between bacteria (3)

Conjugation occurs by direct contact between two bacteria, plasmids from

a mating bridge across the bacteriaand DNA is exchanged, which can
result in acquisition of antibiotic-resistance genes by the recipient cells
Transposons are sequences of DNA that carry their own recombination
enxymes that allow for transposition from one location to another,
transposons can also carry antibiotic-resistance genes
 Cost of anti-microbial resistance

Cheap antimicrobials become ineffective

Individual treatment failure
Prolonged illness, hospitalization
Need to switch to more expensive, complex drugs that are
often not even available in resource-poor settings
Need to develop new antimicrobials

Good antimicrobial susceptibility testing saves lives and

money
Key Prevention Strategies

Prevent infection
Diagnose and treat
infection effectively
Use antimicrobials
wisely
Prevent transmission

Clinicians hold the solution

 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults

12 Steps to Prevent Antimicrobial Resistance:

Hospitalized Adults
Clinicians hold the solution
Take steps NOW to prevent antimicrobial resistance!

12 Contain your contagion

11 Isolate the pathogen Prevent Transmission
10 Stop treatment when cured
9 Know when to say no to vanco
8 Treat infection, not colonization Use Antimicrobials Wisely
7 Treat infection, not contamination
6 Use local data
5 Practice antimicrobial control
4 Access the experts
3 Target the pathogen Diagnose and Treat Effectively
2 Get the catheters out
1 Vaccinate Prevent Infection
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

PREVENTION
IS
PRIMARY

Protect patients
protect healthcare personnel
promote quality healthcare!
National Center for Infectious Diseases
 WHO/CDS/CSR/APH/2000.4
Distr. : General
English only

WHO Global Principles For

The Containment of Antimicrobial
Resistance In Animals Intended
for Food
Report of a WHO Consultation
with the participation of the Food and Agriulture Organization and the
Office International des Epizooties

Geneva, Switzerland
5 9 June 2000

Department for Communicable Diseases Surveillance and Response

World Health Organization