Microbiology- a clinical approach by Anthony
Strelkauskas et al. 2010
Chapter 20: Antibiotic resistance
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The most important problem associated with
infectious disease today is the rapid
development of resistance to antibiotics.
Health care personnel has an immediate impact
on the development of antibiotic resistance.
MRSA, VRSA, VRE,
Acinetobacter
baumannii, ESBL
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There are several factors in the development
of antibiotic resistance:
◦ Bacteria have typically a short generation time and
reach high numbers during infection.
◦ Considerable potential for rapid spontaneous mutation
 Spontaneous mutation rate is 1 nucleotide per 106 to 1
nucleotide per 1011 base pairs
◦ Some of these mutations are for antibiotic resistance
◦ These mutations are selected for in the presence/use
of an antibiotic.
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Bacterial cells that have
developed resistance are
not killed off.
◦ They continue to divide
◦ Resulting in a completely
resistant population.
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Mutation and evolutionary
pressure cause a rapid
increase in resistance to
antibiotics.
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Modern technology and sociology further
exacerbate development of resistant strains.
Travelers carry resistant bacteria.
They travel with several or many other people.
Other people infected with resistant bacteria.
These people continue traveling and infecting.
The process is repeated and the resistant
bacteria spread.
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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.
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Bacteria pathogenic for
humans colonize animals
(used for consumption)
without causing disease
in the animal.
Widespread use of
antibiotics in agriculture
induces resistance in the
pathogens before they
even have infected
humans.
Antibiotic residual that
is eaten can trigger
resistance in host
microbiota
http://antibioticsfor.com/agriculture.phtml
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An important social change is the increase in
the number of people who are
immunocompromised.
Necessitates increased use of antibiotics.
Fosters development of resistance.
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The most important contributing factor for
resistance is overuse.
A good example is prescribing antibiotics that
don’t kill viruses causing the common “cold.”
These antibiotics do destroy the normal
bacteria flora.
Opportunistic pathogens that are resistant
survive and can take hold.
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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
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Increased use of antibiotics leads to
resistance.
◦ Hospital is a place where resistance can develop
rapidly
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Gene transfer happens via transformation,
transduction, and conjugation.
Resistance can be transferred by bacteria
swapping genes.
◦ This can be easily accomplished in a hospital setting.
◦ Health care workers who don’t follow infection control
protocols aid in increasing resistance.
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Plasmids containing genes for resistance can
integrate into the chromosome.
◦ Here they form resistance islands.
◦ Resistance genes accumulate and are stably
maintained.
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Inactivation of the antibiotic
Keeping antibiotics out
Modification of the antibiotic target
Efflux pumps that remove the antibiotic (and
disinfectants and antiseptics)
Alteration of a metabolic pathway originally
inhibited by the antibiotic
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Extended spectrum beta lactamases.
Plasmid encoded
Found in Gram-negative bacteria such as
Klebsiella.
Enzymes that inactivate all penicillins and
cephalosporines.
Other resistances, such as aminoglycoside
resistance, are often co-transferred on the
same plasmid.
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Bacteria are considered clinically dangerous
because of their antibiotic resistance.
MRSA (methicilin-resistant S. aureus)
VRSA (vancomycin-resistant S. aureus)
VRE (vancomycin-resistant Enterococcus)
VRSA strains are now found throughout the world.
◦ Developing new mechanisms for resistance.
◦ Cell walls for some increased in thickness.
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There are no antibiotic treatments for some MRSA
and VRSA strains.
◦ They are genetically flexible.
◦ They develop resistance to new antibiotics very quickly.
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Acinetobacter baumannii resistance is a new
threat
World wide increase in resistance
Nosocomial infection
Also increased in war zones and natural
disasters; Acinetobacter“iraqii”
Gram-negative rods
Form biofilm which contributes to antibiotic
resistance
Wound infections and septicemia
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The doctor-patient-drug relationship leads to
resistance.
Most clearly seen in the case of common viral
infections.
◦ Patients expect to have antibiotics prescribed.
◦ There is over-prescription of antibiotics that are not
required.
◦ Patients feel better and stop using the drug make the
problem worse by allowing drug-resistant bacteria to
survive and grow.
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The potential for global antibiotic resistance is
due to:
◦ Overuse of antibiotics
◦ Improper adherence to hospital infection control
protocols
◦ Ease of worldwide travel
◦ Difficulty finding new antibiotics
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There are ways to lengthen the useful life of
antibiotics.
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There are ways to
lengthen the useful life
of antibiotics.
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Mutations that confer resistance are selected for by
bacteria.
Travel and modern technology have increased the spread
of antibiotic-resistant pathogens.
One of the most important contributing factors to
antibiotic resistance is the increase in the number of
immunocompromised people.
The time it takes to develop resistance to antibiotics is
relatively short.
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Resistance to an antibiotic can occur through inactivation
of the antibiotic, pumping the antibiotic out of the cell,
modifying the target of the antibiotic, or using
alternative metabolic pathways.
Resistance can be reduced by rotational use or cyclical
patterns of use for antibiotics as well as by using
combinations of different antibiotics together, and
completing the treatment..
A. Gram-positive
bacteria only
B. Gram-negative
bacteria only
C. Both grampositive and
gram-negative
bacteria
D. Ciprofloxacin is
used for
protozoan
infections.
E. Both c and d.
A. Heavy metals inactivate enzymes
B. Surfactants – DNA
C. Alcohols – protein
D. Oxidizing agents nucleic acids
E. Phenol- cell
membrane
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Chapters 18, 19, 20, 21
Multiple Choice, T/F; 25 questions, 50 points
Lecture, Chapter Questions
Please bring Scantron, No. 2 pencil