A breif research on Antibiotic Resistance

1. PHARMACOLOGY II
PHR302
FINAL PRESENTATION

2. AFFILIATION
Submitted To
Dr. Farhana Alam Ripa
Assistant Professor
Department Of Pharmacy
BRAC University
Submitted by
Group F
Mumtahina Zaman: 17146007
Tania Rahman: 17146065
Md. Sharif Hossain: 17346005
Md. Ismail Raju: 17346042
Ashraful Islam: 17346057

3. What Is Antibiotic Resistance?
Antibiotic resistance is the ability of bacteria or other
microbes to resist the effects of an antibiotic. Antibiotic
resistance occurs when bacteria change in some way that
reduces or eliminates the effectiveness of drugs, chemicals,
or other agents designed to cure or prevent infections.
The bacteria survive and continue to multiply causing
more harm.

4. Content
Outline
 Introduction
 Brief History
 Is antibiotic beneficial or harmful?
 Antibiotic misuse
 Factors contributing to antibiotic resistance
 Resistance to antibiotics
 Development of resistance
 Examples of few species
 Mechanisms for acquiring
resistance
 Action of antibiotics on bacterial cell
 Physician’s concern
 Managing the drug resistance problem
 Super infection effect
 Deaths attributable to antibiotic resistance
 Conclusion

5. Brief introduction:
 First discovered in 1929 by A. Fleming. Brought into widespread use in
the 1940s.
 Antibiotic: Of biological origin. Produced by a microbe, inhibits other
microbes.
 Bacteria are rapidly growing organisms. A typical infection that causes
symptoms will contain many bacteria.
 Based on normal genetic variability, this population of bacteria will
have a wide variability of response to an individual antibiotic.
 The treatment of bacterial infections is increasingly complicated by the
ability of bacteria to develop resistance to antibiotics.

7. Antibiotics: Beneficial or Harmful?
 When antibiotics are used, six events may occur
with only one being beneficial:
Antibiotic aids the host defenses to gain control and
eliminate the infection.
 On the other hand…..
•The antibiotic may cause toxicity or allergy.
•Initiate a super infection with resistant bacteria.
•Promote microbial chromosomal mutations to resistance.
•Encourage resistance gene transfer to susceptible species.
•Promote the expression of dormant resistance genes.

8. 1. Taking antibiotics when they are not
needed:
for viral infections
2. When needed, taking antibiotics
incorrectly:
i. Stopping the medicine when you
feel better - not finishing the
prescription
ii. Saving antibiotics for a future
illness
iii. Sharing or using other’s medicine
What is
antibiotic
misuse?

9. Factors
contributing to
antibiotic
resistance
 Travel of people and foodstuffs
 Patient movement within and between
medical institutions
 Socioeconomic factors
 Appropriateness of use
 Poor adherence
 Dose/duration of treatment
overprescribing
 Gene transfer
 Nonantibiotic selection
 Infection control measures

10. Resistance
to
antibiotics
 Denied access: membrane becomes
impermeable for antibiotic: e.g. Imipenem
 Antibiotic modification: some bacteria have
enzymes that cleave or modify antibiotics: e.g.
beta lactamase inactivates penicillin
Altered target site: antibiotic cannot bind to its
intended target because the target itself has been
modified
 Pumping out the antibiotic faster than it gets in:
e.g. tetracyclines
 Alternative target (typically enzyme): e.g.
Alternative penicillin binding protein(PBP2a) in
MRSA

11. Development of resistance:
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.

12. Development
of resistance…

13. Examples of few species that have
developed resistance:
E coli: Development of
Resistance to Third-Generation
Cephalosporins
E coli is a common cause of
urinary tract infections and
bacteremia in humans, and is
frequently resistant to
aminopenicillins, such as
amoxicillin or ampicillin, and
narrow spectrum
S Aureus: Development of
High-Level Vancomycin
Resistance
MRSA is a common cause of
infection among hospitalized
patients. Vancomycin is the
typical treatment for these
infections, but over the last
decade there has been
increasing concern about the
development of MRSA strains
with reduced susceptibility to
vancomycin.
P aeruginosa: Development
of Multidrug Resistance
P aeruginosa is a major cause of
opportunistic infections among
immunocompromised
individuals. The spread of this
organism in healthcare settings
is often difficult to control due
the presence of multiple intrinsic
and acquired mechanisms of
antimicrobial resistance.

14. Mechanism for acquiring
resistance:

15. • An enzyme e.g. Penicillin cleaves a
portion of the antibiotic molecule and
renders it inactive.
•
Drug inactivation
• Mutations can alter the receptor that
transports the drug, so that the drug
cannot enter the cell.
•
Decreased permeability/
change in shape of
receptor
• Specialized membrane proteins are
activated and continually pump the drug
out of the cell.
Activation of drug
pumps
• Some drugs block the usual metabolic
pathway, organisms can circumvent this by using
an alternative, unblocked pathway that produces
the required product.
Use of alternative
metabolic pathway
Mechanism for acquiring
Resistance…

16. Mechanism for acquiring
resistance…

17. Action of antibiotics on bacterial cell

18. There are a
number of
reasons why
bacterial
resistance should
be a concern
for physicians….
First, resistant bacteria, particularly staphylococci, enterococci,
Klebsiella pneumoniae, and Pseudomonas are becoming
commonplace in healthcare institutions.
Bacterial resistance often results in treatment failure, which can have
serious consequences, especially in critically ill patients.
Inadequate empiric antibacterial therapy, defined as the initial use of
an antibacterial agent to which the causative pathogen was not
susceptible, has been associated with increased mortality rates in
patients with bloodstream infections due to resistant species.
The spread of resistant bacteria within the community poses obvious
additional
problems for infection control.
Prolonged therapy with antimicrobial agents, such as vancomycin or
linezolid, may also lead to the development of low-level resistance
that compromises therapy.
Resistant bacteria may also spread and become broader infection-
control problems, not only within healthcare institutions, but in
communities as well.

19. Managing
the Drug
Resistance
Problem
 Limiting the Spread of Drug Resistant Bacteria:
 Use better treatment strategies….Give the
optimal antibiotic.
 Better education of health care professionals
to prevent the prescription of unnecessary antibiotics.
 A second strategy is to ensure that they are
used for the appropriate time. Patient compliance is a
key problem in that respect.
 A third strategy for limiting drug resistance is
to use antibiotic combination
 Phage Therapy:
Phage can be applied on the wounds of a
patient to kill the bacteria, and has proven to be quite
effective. Of course, it cannot be used for internal
infections, and the bacteria might also develop phage
resistance.

20. Managing
the Drug
Resistance
Problem…
 Mobilization of Host Defense Mechanisms:
This can be achieved through the
mobilization of innate immunity such as defensins, or
through the development of vaccines, which make
antibiotics less necessary. The idea is to boost the
immune response capability to control the bacterial
infection. Of course, that approach is not always
successful.
 The Use of Normal Bacterial Flora:
One could also potentially use normal
bacterial flora to suppress some pathogens.
 Development of New Antibiotics:
Although the idea is appealing, in reality,
it is extremely difficult since 99% of the drug candidates
fail, and antibiotics are not as profitable as other, more
commonly used, drugs.

21. The use of broad-spectrum antibiotics rather than narrow-
spectrum drugs is known to favor the emergence of resistance
by broadly eliminating competing susceptible flora, leading to
the rise in resistance. It permits the SUPER INFECTION effect.

22. Deaths attributable to antibiotic
resistance every year by 2050

23. CONCLUSION
 Through billions of years of evolution, microbes have developed myriad
defense mechanisms designed to ensure their survival. This protection is
readily transferred to their fellow life forms via transposable elements.
 Despite very early warnings, humans have chosen to abuse the gift of
antibiotics and have created a situation where all microorganisms are
resistant to some antibiotics and some microorganisms are resistant to all
antibiotics.
 Finally, antibiotics are ‘‘societal drugs’’ that affect microbial resistance not only
in the person taking the drug but also everyone else, because resistance
genes are easily passed.
 Improving hygiene in hospitals, Screening of hospital visitors and isolating
patients can control the spread of resistance to some extent.

24.  The impact of antibiotic use on resistance development
and persistence Teresa M. Barbosa,1 Stuart B. Levy 1,2
 Mechanisms of Antibiotic Resistance in the Microbial
World Ying ZHANG ,Baltimore, USA
 Mechanisms of Antimicrobial Resistance in Bacteria
Fred C. Tenover, PhD
 Division of Healthcare Quality Promotion, Centers for
Disease Control and Prevention, Atlanta, Georgia, USA
 http://www.who.int/drugresistance/amr_q&a.pdf
 http://biomed.emory.edu/PROGRAM_SITES/PBEE/pdf/ten
over1.pdf
 http://www.accesspharmacy.com/content.
Reference