Antibiotic resistance is a serious problem which we have to tackle by various steps and measures.

1. 0VERVIEW OF ANTIBIOTIC RESISTANCE
Presented by – Krishna V. Supalkar
FY M. Pharm Pharmacology
Guided by – Dr. Smita Sadar
Dr. DY Patil college of pharmacy, akurdi,pune

2. What are antibiotics ?
• Antibiotics : chemical produced by a
microorganism that kills or inhibit the growth of
another microorganism.
• Also called as antibacterials or antimicrobials
• They work by inhibiting the growth of or
destroying the bacteria.
• Anti- against, Biotic- life
• Antibiotics only work against infections caused
by bacteria and certain parasites.
• e.g. penicillin, cephalosporins, tetracyclines,
aminoglycosides, macrolides.

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. Why antibiotic resistance is a serious problem ?
• Resistant organism lead to treatment failure
• Increased mortality
• Resistant bacteria may spread in community
• Low level resistance can go undetected
• Added burden on healthcare costs
• Threatens to return to pre-antibiotic era
• Selection pressure

5. Mechanism of antibiotic resistance :
Enzymatic
modification
Decreased
permeability of
Bacterial
membranes
Promotion of
antibiotic Efflux
Altered target
sites.
Overproduction
of target
Bypass of
antibiotic
inhibition

7. Enzyme modification
• By production of enzymes that inactivates the antibiotic.
• Beta lactamase enzyme – beta lactam antibiotics (S. aureus, N. gonorrhea, H.
influenza)
• Chloramphenicol acetyl transferase – chloramphenicol
(gram –ve > gram +ve).
• Acetyl transferases, phosphotransferases and adenyltransferases -
aminoglycosides

8. Altered target site :
A common mechanism that bacteria use to become resistant to antibiotics
is by modifying the target of the antibiotics.
As bacteria grow and replicate they copy their genetic material.
When they do this, occasionally mistakes in the DNA sequences get
included (e.g. an A gets replaced with a C). These mistakes only happen
very rarely, but the very large population size (billions and trillions) of
bacteria, means that this happens frequently enough that occasionally
these mutations are present in bacterial populations in the presence of
antibiotics.
If one of these mutations happens to be at a location of a gene that
encodes for a protein that is the target of an antibiotic, then sometimes
these mutations mean that the antibiotic can no longer bind to the target.
This means that the bacteria with the mutation will have a growth
advantage and survive the antibiotic while the rest of the population will
die.
Common mechanism for resistance to penicillin in streptococcus
pneumonia.

9. Reduced membrane permeability
• Another common way of interfering with antibiotics is through the
prevention of entrance of the drug into the cell.
• Gram negative bacteria have an outer cell membrane, and drugs must
pass through the cell pores, which are channels that the span the
outer membrane and allow the entry and exit of materials into or out
of the cell. In order to enter the cell or interact with the cell wall, the
drugs must be able to pass through the pores.

10. Efflux Or Transport Of Antibiotic
• An efflux pump is a biological pump that can force the
antibiotic out of the cell, so that it cannot reach or stay in
contact with its target.
• This method of antimicrobial may often create resistance to
more than one class of antibiotics, especially the
macrolides, tetracyclines and fluoroquinolones because
these antibiotics inhibit different aspects of protein and
DNA biosynthesis and therefore must be intracellular to
exert their effect

11. Modify or bypass the target of the antibiotic
• Camouflage the target :-
• Changes in the composition or structure of the target in the bacterium (resulting
from mutations in the bacterial DNA) can stop the antibiotic from interacting with
the target.
• Alternatively, the bacteria can add different chemical groups to the target
structure, in this way shielding it from the antibiotic.

13. Classification of antibiotics :
 On the basis of spectrum activity :
Broad spectrum antibiotics :
• Amoxicillin
• Tetracycline
• Cephalosporins
• Chloramphenicol
• Erythromycin
Short acting antibiotics :
• Penicillin G
• Cloxacillin
• Vancomycin
• bacitracin

14.  On the basis of mode of action:
Bacteriostatic antibiotics :
• Tetracycline
• Chloramphenicol
• Erythromycin
• Lincomycin
Bactericidal antibiotics
• Cephalosporin
• Penicillin
• Aminoglycosides
• Cotrimoxazole

15. Detecting Methods Of Antimicrobial Resistance
• Disk diffusion method
• Dilution method
• Broth dilution method
• Agar dilution method
• Automated instrument method :
micro scan, walk away, BD phonix,
Trek sensititere
• Molecular methods : PCR, MALDITOF
MS.

16. This Photo by Unknown Author is licensed under CC BY

17. Example of resistance
• Tuberculosis (TB)
• Methicillin resistant staphylococcus aureus (MRSA)
• Gonorrhea
• HIV
• Fungal infections
• Malaria
• H. pylori infection

18. Drug
resistance
Natural
resistance
Acquired
resistance
• Some microbes have always been resistant
to certain AMAs
• They lack the metabolic process or the
target sites which is affected by the
particular drug.
• E.g. gram-negative bacilli are unaffected
by penicillin G
• This type of resistance does not pose a
significant clinical problem.
• Development of resistance by an organism (which
was sensitive before) due to use of an AMA over a
period of time.
• Some bacteria get rapid acquisition of resistance e.g.
staphylococci, coliforms, tubercle bacilli.
• Others like strep. Pyrogens and spirochetes have not
developed significant resistance to penicillin despite
its widespread use for >60 years.
• Pose a significant problem

19. Cross Resistance
• Acquisition of resistance to one AMA conferring resistance to another AMA , to which the
organism has not been exposed, is called CROSS RESISTANCE
• This is more commonly seen between chemically related drugs
• E.g.-resistance to one sulfonamide means resistance to all other sulfonamides
• Resistance to one tetracycline means insensitivity to all other tetracyclines.
• Resistance to one aminoglycoside may not extend to another
- e.g. gentamicin-resistance strains may not respond to amikacin
• Unrelated drugs show partial cross resistance
- e.g. tetracyclines and chloramphenicol, erythromycin and lincomycin.

20. Resistant
organisms
Drug
tolerant Drug
destroying
Drug
impermea
The target biomolecules of the
microorganism loses affinity for a
particular AMA
e.g. certain penicillin-resistant
pneumococcal strains have altered
penicillin binding proteins.
The resistant microbe elaborates
enzyme which inactivates drug
-beta lactamases are produced by
staphylococci, Haemophilus,
gonococci which inactivate
penicillin G
Many hydrophilic antibiotics gain
access into the bacterial cell
through specific channels
formed by proteins called
porins.
- These porins may be lost by the
resistant strains
- e.g. concentration of some
aminoglycosides and
tetracyclines in the resistant
gram-negative bacterial strains
has been found to be much
lower than that in their sensitive
counterparts
Another mechanism is
acquisition of an alternative
pathway.
e.g. sulfonamide resistant
bacteria switch over to
utilizing. Performed folic
acid in place of synthesizing
it from PABA

23.  Causes of antibiotic resistance :
1. Over prescription of Antibiotics
2. Patient not finishing the entire antibiotic course
3. Overuse of antibiotics in livestock and fish farming
4. Poor infection control in health care settings
5. Poor hygiene and sanitation
6. Absence of new antibiotics being discovered

24. Management of antibiotic resistance
Reduce the need for antibiotic through improved water, sanitation, and immunization
Improve hospital infection control and antibiotic stewardship
Change incentives that encourage antibiotic overuse and misuse to incentives that
encourage antibiotic stewardship
Reduce and eventually phase out subtherapeutic antibiotic in agriculture
Educate health professionals policy makers, and the public on sustainable
antibiotic use
Ensure political commitment to meet the threat antibiotic resistance

25. Management Of Antibiotic Resistance
Prevent Transmission Of Bacterial Infections
• Diligent hand hygiene before and after all patient interactions that take place
during the delivery of health care
• Disinfection of the health care environment and patient-care equipment
• Development of new vaccines can be effective in limiting the transmission of
resistant bacterial infections. For e.g. The new streptococcus pneumoniae vaccine
in 2010.
• Improving access to clean water and sewerage systems, and ensuring a safe and
healthful food supply.
• Establishment of regulations governing the discharge of antimicrobial waste into
the environment for prevention of environmental antibiotic pollution.

26. Management Of Antibiotic Resistance
Individuals
• Only use antibiotics when prescribed by a certified health
professional.
• Never demand antibiotics if your health worker says you don’t
need them.
• Always follow your health worker’s advice when using
antibiotics.
• Never share or use leftover antibiotics.
• Prevent infections by regularly washing hands, preparing food
hygienically, avoiding close contact with sick people, practicing
safer sex, and keeping vaccination up to date.

27. • Take antibiotics as prescribed
• Do not skip the doses
• Do not save antibiotics
• Do not take antibiotics prescribed for someone else
• Talk with your health care professional
• All drugs have side effects

28. Management Of Antibiotic Resistance
 Agriculture sector
To prevent and control the spread of antibiotic resistance, the
agriculture sector can :
 Only give antibiotics to animals under veterinary supervision.
 Not use antibiotics for growth promotion or to prevent disease
in healthy animals.
 Vaccinate animals to reduce the need for antibiotics and use
alternatives to antibiotics when available.
 Promote and apply good practices at all steps of production
and processing of foods from animal and plant sources.
 Improve biosecurity on farms and prevent infections through
improved hygiene and animal welfare.

29. Management Of Antibiotic Resistance
Policy makers
 Ensure a robust national action plan to tackle antibiotic resistance is
in place.
 Improve surveillance of antibiotic-resistant infections.
 Strengthen policies, programs, and implantation of infection
prevention and control measures.
 Regulate and promote the appropriate use and disposal of quality
medicines.
 Make information available on the impact of antibiotic resistance.

30. Management Of Antibiotic Resistance
Health professionals :
• Prevent infections by ensuring your hands, instruments,
and environment are clean.
• Only prescribe and dispense antibiotics when they are
needed, according to current guidelines.
• Report antibiotic-resistant infections to surveillance
teams.
• Talk to your patients about how to take antibiotics
correctly, antibiotic resistance and the dangers of misuse.
• Talk to your patients about preventing infections (for e.g.
vaccination, hand washing, safer sex and covering nose
and mouth when sneezing.)

31. Management Of Antibiotic Resistance
Health Care Industry :
 Invest in research and development of new
antibiotics, vaccines, diagnostic and other
tools.

32. Management Of Antibiotic Resistance
Adopt Antibiotic Stewardship Programs
• Guide all prescribers in administering antibiotics
correctly.
• Making a commitment to use antibiotics only when
needed.
• Choose the proper drug, and administer the
medication at the appropriate dose and duration in
every case.
• Requires an interdisciplinary team system
innovation, educational intervention, and feedback
provided to health workers.
• Improve patient care, shorten hospital stays, and
reduce health care facilities pharmacy cost.

33. What are the alternatives ?
• Bacteriophage : using a virus that consumes bacteria in drug form
• Bacteriocins
• Monoclonal antibodies : combat the effects of the toxins that the microbes
produce
• Developing vaccines
• Fecal microbiota transplant : involves taking good bacteria from a healthy
person’s gut and transplanting them into a recipient who is lacking them
• Probiotics
• Antivirulence drugs

34. This Photo by Unknown Author is licensed under CC BY

36. side effects of antibiotics :
Digestive problems
Photosensitivity
Staining
Anaphylaxis
Kidney disease
Allergy

37. National Action Plan On Antimicrobial Resistance
• Goal : The overarching goal of the National action plan on
antimicrobials resistance (NAP-AMR) is to effectively combat
antimicrobial resistance in India, and contribute towards the global
efforts to tackle this public health threat.

38. Strategic priorities of NAP-AMR
1. Improve awareness
and understanding of
AMR through effective
communication,
education and training
2. Strengthen
knowledge and
evidence through
surveillance
3. Reduce the incidence
of infection through
effective infection
prevention and control.
4. Optimize the use of
antimicrobial agents in
health, animals and
food
5. Promote investments
for AMR activities,
research and
innovations
6. Strengthen India’s
leadership on AMR

39. Stewardship program
• Antimicrobial stewardship has been defined as “the optimal selection,
dosage, and duration of antimicrobial treatment that results in best
clinical outcome for the treatment or prevention of infection, wit
minimum toxicity to the patient and minimal impact on subsequent
resistance.
• The goal of antimicrobial stewardship is 3-fold
1. The first is to work with health care practitioners to help each patient
receive the most appropriate antimicrobial with the correct dose and
duration
2. Prevent antimicrobial overuse, misuse and abuse.
3. Minimize the development of resistance.

40. Antibiotics are a precious
resource
We need to preserve this
resource by working together
Combating antimicrobial
resistance: No action today, no
cure tomorrow.

41. References
• Antibiotic resistance : A global concern
http://www.slideshare.net/RohanJagadale2/antibiotic-resistance-a-global-concern-243645940?from_m_app=android
• Mechanism of development for drug resistance
http://www.slideshare.net/NikitaIngale4/mechanism-of-development-for-drug-resistance?from_m_app=android
• management-of-antibiotic-resistance http://www.slideshare.net/AnimeshGupta29/management-of-antibiotic-resistance-
upload?from_m_app=android
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351036/#:~:text=Destruction%20or%20modification%20of%20the,10
• antibiotic-resistance
https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
• https://www.frontiersin.org/articles/10.3389/fmicb.2018.02928/full
• Antimicrobial_resistance_in_India_A_review
https://www.researchgate.net/publication/257250882_Antimicrobial_resistance_in_India_A_review