RESISTENSI MIKROBA TERHADAP

ANTIBIOTIKA
 DEFENITION

Antimicrobial resistance (AMR) is resistance

of a microorganism to an antimicrobial drug
that was originally effective for treatment of
infections caused by it.
WHY IS THIS IMPORTANT?

The most important problem associated with

infectious disease today is the rapid development of
resistance to antibiotics.
It will force us to change the way we view disease
and the way we treat patients.
ANTIBIOTIC RESISTANCE

Antibiotics use has not been without consequence.

There are several factors in the development of
antibiotic resistance:
Considerable potential for rapid spontaneous mutation
Some of these mutations are for antibiotic resistance
These mutations are selected for certain antibiotics.
DEVELOPMENT OF RESISTANCE

Bacterial cells that have developed resistance are not

killed off.
They continue to divide
Resulting in a completely resistant population.
..DEVELOPMENT OF RESISTANCE
DEVELOPMENT OF RESISTANCE:
Travel

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:
Living Conditions

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:
Food

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.
DEVELOPMENT OF RESISTANCE:
Immunocompromised Patients

An important social change is the increase in the

number of people who are immunocompromised.
Necessitates increased use of antibiotics
Fosters development of resistance
DEVELOPMENT OF RESISTANCE:
Emerging and Re-emerging Diseases

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.
EVOLUTION OF ANTIBIOTIC RESISTANCE

The clinical success of antibiotics led to:

Increasing efforts to discover new antibiotics.
Modification of existing drugs.
Development of antibiotics with broader spectra.

Effort is now targeted towards overcoming strains

resistant to current antibiotics.
EVOLUTION OF RESISTANCE TO ANTIBIOTIC
..EVOLUTION OF ANTIBIOTIC
RESISTANCE: Rate of Development
Resistance develops at different rates.
Several groups of antibiotics were used for many years
before resistance was seen.
Resistance to penicillin was seen in only three years.
Some semi-synthetic forms of penicillin (ampicillin)
had a relatively long time before resistance developed.
Other semi-synthetic forms (methicillin) lasted only a
year before resistance developed.
Short interval is directly related to increased use.
..EVOLUTION OF ANTIBIOTIC
RESISTANCE: Rate of Development

The therapeutic life span of a drug is based on how

quickly resistance develops.
The more an antibiotic is used, the more quickly
resistance occurs.
..EVOLUTION OF ANTIBIOTIC
RESISTANCE: Rate of Development
..EVOLUTION OF ANTIBIOTIC
RESISTANCE: Overuse

The most important contributing factor for resistance

is overuse.
A good example is prescribing antibiotics that dont
kill viruses for the common cold.
These antibiotics do destroy the normal flora.
Opportunistic pathogens that are resistant survive and
can take hold.
EVOLUTION OF ANTIBIOTIC RESISTANCE:
Hospitals

Hospitals are ideal reservoirs for the acquisition of

resistance.
A population of people with compromised health
A high concentration of organisms, many of which are
extremely pathogenic
Large amounts of different antibiotics are constantly
in use
Increased use of antibiotics leads to resistance.
Hospital is a place where resistance can develop
rapidly.
..EVOLUTION OF ANTIBIOTIC RESISTANCE:
Transfer

Resistance can be transferred by bacteria swapping

genes.
This can be easily accomplished in a hospital setting.
Health care workers who dont follow infection control
protocols aid in increasing resistance.
..EVOLUTION OF ANTIBIOTIC RESISTANCE:
Resistance Islands

Plasmids containing genes for resistance can integrate

into the chromosome.
Here they form resistance islands.
Resistance genes accumulate and are stably
maintained.
Antibiotic mechanism
A schematic of a normal peptidoglycan cell wall

NAG (N-acetylglucosamine)
NAM (N-acetlymuramic acid)
Mechanisms of Antimicrobial Action

Inhibition of Cell Wall Synthesis

Inhibition of bacterial wall synthesis
Most common agents prevent cross-linkage of
NAM subunits
Beta-lactams are most prominent in this group
Functional groups are beta-lactam rings
Beta-lactams bind to enzymes (transpeptidase)
which are Penicillin binding protein (PBP) that
cross-link NAM subunits
Bacteria have weakened cell walls and
eventually lyse

2012 Pearson Education Inc.

The effect of penicillin on peptidoglycan in preventing NAM-NAM cross-links

Mechanisms of Resistance in Gram-negative Bacteria

to Beta-Lactam Antibiotics.mp4
Mechanisms of Antimicrobial Action

Inhibition of Cell Wall

Synthesis
Inhibition of synthesis of
bacterial walls
Vancomycin and
cycloserine
Interfere with bridges
that link NAM subunits in
many Gram-positives
Bacitracin
Blocks secretion of NAG
and NAM from cytoplasm
Mechanisms of Antimicrobial Action

Inhibition of Cell Wall Synthesis

Inhibition of synthesis of bacterial walls
Prevent bacteria from increasing amount of
peptidoglycan
Have no effect on existing peptidoglycan layer
Effective only for growing cells

2012 Pearson Education Inc.

Mechanisms of Antimicrobial Action

Inhibition of Protein Synthesis

Prokaryotic ribosomes are 70S (30S and 50S)
Eukaryotic ribosomes are 80S (40S and 60S)
Drugs can selectively target translation
Mitochondria of animals and humans contain 70S
ribosomes
Can be harmful

2012 Pearson Education Inc.

The mechanisms by which antimicrobials inhibit protein synthesis-overview

Macrolides- Mechanisms of Action and Resistance (1).mp4

Mechanisms of Antimicrobial Action

Inhibition of Metabolic Pathways

Antimetabolic agents can be effective when
metabolic processes of pathogen and host differ
Quinolones interfere with the metabolism of
malaria parasites

2012 Pearson Education Inc.

Antimetabolic action of sulfonamides-overview
Mechanisms of Antimicrobial Action

Inhibition of Nucleic Acid Synthesis

Several drugs block DNA replication or
mRNA transcription
Drugs often affect both eukaryotic and
prokaryotic cells
Not normally used to treat infections
Used in research and perhaps to slow cancer
cell replication

2012 Pearson Education Inc.

Mechanisms of Antimicrobial Action

Inhibition of Nucleic Acid Synthesis

Quinolones and fluoroquinolones
Act against prokaryotic DNA gyrase
Fluoroquinolon resistance.MP4
Inhibitors of RNA polymerase during
transcription

The Animation of Antimicrobial Resistance.mp4

2012 Pearson Education Inc.