The document discusses antibiotic resistance. It begins by defining antibiotics and antibiotic resistance, noting that antibiotic resistance occurs when bacteria change in response to antibiotic use and become harder to treat. It then discusses the scope of the problem, highlighting that antibiotic resistance threatens global health and development. The document also provides timelines of resistance emerging to various antibiotics. It discusses mechanisms of resistance, such as bacteria modifying targets, and reasons for a lack of new antibiotic development, such as scientific and economic challenges.

1. Presented by-
ROHAN JAGDALE
B. Pharm
YTIP, University Of Mumbai
Presented by-
ROHAN JAGDALE
B. Pharm student
YTIP, University Of Mumbai
Antibiotic Resistance

2. ❖ Introduction
❖ Bacteria
❖ What is antibiotic resistance?
❖ Scope of the problem
❖ Timeline of antibiotics resistance
❖ Mechanism of antibiotics resistance
❖ Why don't we develop more antibiotics
❖ Alternative to Antibiotics
❖ Prevention and control
Contents

3. Introduction
Antibiotics are medicines used to prevent and treat bacterial
infections. Antibiotic resistance occurs when bacteria change in
response to the use of these medicines.
Bacteria, not humans or animals, become antibiotic-resistant.
These bacteria may infect humans and animals, and the infections
they cause are harder to treat than those caused by non-resistant
bacteria.
Antibiotic resistance leads to higher medical costs, prolonged
hospital stays, and increased mortality.

4. The world urgently needs to change the way it prescribes and uses
antibiotics. Even if new medicines are developed, without
behaviour change, antibiotic resistance will remain a major threat.
Behaviour changes must also include actions to reduce the spread
of infections through vaccination, hand washing, practising safer
sex, and good food hygiene.

5. Key facts
● Antibiotic resistance is one of the biggest threats to global health,
food security, and development today.
● Antibiotic resistance can affect anyone, of any age, in any country.
● Antibiotic resistance occurs naturally, but misuse of antibiotics in
humans and animals is accelerating the process.
● A growing number of infections – such as pneumonia, tuberculosis,
gonorrhoea, and salmonellosis – are becoming harder to treat as the
antibiotics used to treat them become less effective.
● Antibiotic resistance leads to longer hospital stays, higher medical
costs and increased mortality.

6. Bacteria : the most abundant and earliest living form
Bacteria have existed from very early in the history of life on Earth. Bacteria
fossils discovered in rocks date from at least the Devonian Period (419.2
million to 358.9 million years ago), and there are convincing arguments that
bacteria have been present since early Precambrian time, about 3.5 billion
years ago. Bacteria were widespread on Earth at least since the latter part of
the Paleoproterozoic, roughly 1.8 billion years ago, when oxygen appeared in
the atmosphere as a result of the action of the cyanobacteria. Bacteria have
thus had plenty of time to adapt to their environments and to have given rise
to numerous descendant forms.
That's why all scientists and microbiologist thinks they are much
ahead than us in case of living and they are hard & complicated to
understand

7. Bacteria
Bacteria are small (microscopic size) organisms that can
be found in most environments, for example in soil, water
and on and inside the human body
• There are around 50 million bacteria
in every gram of surface soil
• We would not survive without them!
– Help degrade the food we eat
– Protect against pathogens

8. DISEASE-CAUSING BACTERIA
A few bacteria can be dangerous to our health by causing
infections and even death
• We can get them from outside the body:
– Other humans, animals, food, water
• Sometimes our “own” bacteria can cause disease
• Examples of bacterial infections:
– Pneumonia
– Blood stream infections
– Urinary tract infections
– Wound infections
– The sexually transmitted disease gonorrhea

9. Antibiotics
Antibiotics are medicines for bacterial infections
• Examples of antibiotics:
– Penicillin and Ciprofloxacin
• Penicillin was discovered by Alexander Fleming in 1928
– Introduced as medicine in the 1940’s
• Antibiotics can have “broad” or “narrow” spectrum
– Broad spectrum: Active against many different types of bacteria
– Narrow spectrum: Active against one or a few types of bacteria

10. What is antibiotic resistance?
Antibiotic resistance happens when the germs no longer respond to
the antibiotics designed to kill them. That means the germs are not
killed and continue to grow. It does not mean our body is resistant to
antibiotics.
Bacteria and fungi are constantly finding new ways to avoid the
effects of the antibiotics used to treat the infections they cause.
Infections caused by antibiotic-resistant germs are difficult, and
sometimes impossible, to treat. In many cases, antibiotic-resistant
infections require extended hospital stays, additional follow-up
doctor visits, and costly and toxic alternatives.

12. How antibiotic resistance happens

13. Scope of the problem
Antibiotic resistance is rising to dangerously high levels in all parts of the world.
New resistance mechanisms are emerging and spreading globally, threatening our
ability to treat common infectious diseases. A growing list of infections – such as
pneumonia, tuberculosis, blood poisoning, gonorrhoea, and foodborne diseases –
are becoming harder, and sometimes impossible, to treat as antibiotics become
less effective.
Where antibiotics can be bought for human or animal use without a prescription,
the emergence and spread of resistance is made worse. Similarly, in countries
without standard treatment guidelines, antibiotics are often over-prescribed by
health workers and veterinarians and over-used by the public.
Without urgent action, we are heading for a post-antibiotic era, in which common
infections and minor injuries can once again kill.

14. Time line of antibiotics resistance
Antibiotic
Approved or
Released
Year Released Resistant Germ
Identified
Year Identified
Penicillin 1941 Penicillin-resistant
Staphylococcus
aureus
Penicillin-resistant
Streptococcus
pneumoniae
Penicillinase-produci
ng Neisseria
gonorrhoeae
1942.
1967
1976

15. Antibiotic
Approved or
Released
Year Released Resistant Germ
Identified
Year Identified
Vancomycin 1958 Plasmid-mediated
vancomycin-resistan
t Enterococcus
faecium
Vancomycin-resista
nt Staphylococcus
aureus
1988
2002
Amphotericin B 1959 Amphotericin
B-resistant Candida
auris
2016
Methicillin 1960 Methicillin-resistant
Staphylococcus
aureus
1960

16. Antibiotic
Approved or
Released
Year Released Resistant Germ
Identified
Year Identified
Extended-spectrum
cephalosporins
1980 (Cefotaxime) Extended-spectrum
beta-lactamase-
producing
Escherichia coli
1983
Azithromycin 1980 Azithromycin-resista
nt Neisseria
gonorrhoeae
2011
Imipenem 1985 Klebsiella
pneumoniae
carbapenemase
(KPC)-producing
Klebsiella
pneumoniae
1996
Ciprofloxacin 1987 Ciprofloxacin-resista
nt Neisseria
gonorrhoeae
2007

17. Antibiotic
Approved or
Released
Year Released Resistant Germ
Identified
Year Identified
Fluconazole 1990 (FDA
approved)
Fluconazole-resistan
t Candida
1988
Caspofungin 2001 Caspofungin-resista
nt Candida
2004
Daptomycin 2003 Daptomycin-resistan
t methicillin-resistant
Staphylococcus
aureus
2004
Ceftazidime-avibact
am
2015
Ceftazidime-avibact
am-resistant
KPC-producing
Klebsiella
pneumoniae
2015

19. Antibiotics Resistance Mechanism

20. 1.Stop the antibiotic from reaching its target
▪Pump the antibiotic out from the bacterial cell.:-
Bacteria can produce pumps that sit in their membrane or cell
wall. These so-called efflux pumps are very common in bacteria
and can transport a variety of compounds such as signal molecules
and nutrients. Some of these pumps can also transport antibiotics
out from the bacterium, in this way lowering the antibiotic
concentration inside the bacterial cell. In some cases mutations in
the bacterial DNA can make the bacteria produce more of a certain
pump, which in turn increases resistance.

21. ▪Decrease permeability of the membrane that surrounds the bacterial
cell.:- Certain changes in the bacterial membrane make it more
difficult to pass through. In this way, less of the antibiotic gets into
the bacteria.
▪Destroy the antibiotic.:- There are bacterial enzymes that can
inactivate antibiotics. One example is β-lactamase that destroys the
active component (the β-lactam ring) of penicillins, extremely
important antibiotics for treating human infections. In later years,
bacteria that produce extended-spectrum β-lactamases, so called
ESBL-producing bacteria, have become a major problem. They can
degrade a wide spectrum of β-lactam antibiotics, sometimes also the
last resort drugs available for infections with these bacteria.

22. ▪Modify the antibiotic. :-
Bacteria can sometimes produce enzymes that are capable of
adding different chemical groups to antibiotics. This in turn
prohibits binding between the antibiotic and its target in the
bacterial cell.

23. Antibiotic resistance strategies in bacteria.

24. 2.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.

25. ▪Express alternative proteins.:-
Some bacteria are able to produce alternative proteins that can
be used instead of the ones that are inhibited by the antibiotic.
For example, the bacterium Staphylococcus aureus can acquire
the resistance gene mecA and produce a new penicillin-binding
protein. These proteins are needed for bacterial cell wall
synthesis and are the targets of β-lactam antibiotics. The new
penicillin-binding protein has low affinity to β-lactam
antibiotics and is thus resistant to the drugs, and the bacteria
survive treatment. This type of resistance is the basis in MRSA
(methicillin-resistant Staphylococcus aureus).

26. ▪Reprogram target.:-
Sometimes bacteria can produce a different variant of a structure it
needs. For example, Vancomycin-resistant bacteria make a different
cell wall compared to susceptible bacteria. The antibiotic is not able to
interact as well with this type of cell wall.

27. Schematic diagram highlighting the antibiotic resistance mechanisms
utilized by bacteria. MDR pathogens can employ one or more of these
mechanisms to become resistant to a diverse array of antibiotics.

28. Some bacteria are naturally resistant to certain antibiotics.
Imagine for example an antibiotic that destroys the cell wall
of the bacteria. If a bacterium does not have a cell wall, the
antibiotic will have no effect. This phenomenon is called
intrinsic resistance. When a bacterium that was previously
susceptible to an antibiotic evolves resistance it is called
acquired resistance.

29. Intrinsic resistance
Resistance to specific antibiotics is a natural characteristic of some bacteria. This
is known as intrinsic resistance. Bacteria in nature often produce antibiotics
(many of which are the same as the ones used in the clinic) to compete with nearby
bacteria – obviously, this is only a good competitive strategy if a bacterium is
resistant to the antibiotics it produces! Intrinsic resistance can work in two ways:
either the bacterium already has resistance genes in its genome, or it lacks the
target of the antibiotic. Intrinsic resistance is one reason why improved diagnostic
tests would be so useful – Klebsiella pneumoniae, Staphylococcus aureus and
Pseudomonas aeruginosa are responsible for a large proportion of
hospital-acquired infections, but each of these species is intrinsically resistant to
some antibiotics, making it very difficult to choose the right one.

30. Missing drug target: Polymyxin and the
bacterial outer membrane
All bacterial cells are surrounded by a membrane, that acts as a barrier between
the outside of the cell and the inside. Gram-positive bacteria (named after their
result in a Gram stain test) have a single cell membrane inside a thick cell wall.
Gram-negative bacteria instead have an inner and an outer cell membrane, with a
thin cell wall in between them. Polymyxin is an antibiotic that targets both
membranes of a Gram-negative bacterium and makes them unstable and leaky,
resulting in death of the cell. In Gram-positive bacteria the thick cell wall prevents
polymyxin from reaching the cell membrane (and there is no outer membrane), so
bacterial species in this category, such as S. aureus are intrinsically resistant to
polymyxin.

31. Efflux pumps
Bacterial efflux pumps are membrane protein complexes which
transport molecules from the inside of the cell to the outside.
Some of these pumps can transport antibiotics, including those
that have entered the cell from the outside. Bacteria with efflux
pumps specific to a class of antibiotic will expel these drugs, and
therefore be resistant. For example, the bacterium Pseudomonas
aeruginosa, which causes chronic infections in cystic fibrosis
patients, has high intrinsic resistance to aminoglycoside class
antibiotics because it produces two efflux pumps active against
this class of drug.

32. Detoxifying enzymes
Many bacteria produce enzymes that degrade or inactivate
specific antibiotics. For example, many bacteria produce
beta-lactamase enzymes that break down penicillin-family
antibiotics (which contain a beta-lactam ring). Similarly,
aminoglycoside antibiotics can be inactivated by enzymes
that modify them and prevent them binding to their target.

33. Intrinsic resistance or acquired resistance?
Efflux pumps, beta-lactamases and aminoglycoside-modifying
enzymes can also be acquired by gene transfer from other bacteria
. So, how do we know if resistance to a drug is intrinsic or
acquired, when the mechanism of resistance can be the same?
Intrinsic resistance normally describes a characteristic that is
shared across a whole species or lineage of bacterial strains, and
where the relevant genes are stably carried rather than being
found on mobile DNA elements such as plasmids. Genomic
analysis can give a high resolution picture of the spread and
origins of AMR in groups of bacteria.

34. AMR mechanisms in bacteria

35. Method of resistance Antibiotics
Reduced uptake into cell Chloramphenicol
Active efflux from the cell Tetracycline
Eliminated or reduced binding of antibiotic to cell
target
β-Lactams, erythromycin, lincomycin
Enzymic cleavage or modification to inactivate
antibiotic molecule
β-Lactams, aminoglycosides, chloramphenicol
Metabolic bypass of inhibited reaction Sulfonamides, trimethoprim
Overproduction of antibiotic target Sulfonamides, trimethoprim
Examples of methods of antibiotic resistance

36. Main causes of antibiotic resistance
1. Over-prescription of antibiotics
2. Patients 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

37. How can taking antibiotics contribute to
antibiotic resistance?
Anytime antibiotics are used, they can contribute to antibiotic resistance. This
is because increases in antibiotic resistance are driven by a combination of
germs exposed to antibiotics, and the spread of those germs and their
mechanisms of resistance. When antibiotics are needed, the benefits usually
outweigh the risks of antibiotic resistance. However, too many antibiotics are
being used unnecessarily and misused, which threatens the usefulness of
these important drugs.
Everyone has a role to play in improving antibiotic use. Appropriate antibiotic
use helps fight antibiotic resistance and ensures these lifesaving drugs will be
available for future generations.

38. Why don't we develop more antibiotics?
If bacteria are developing resistance to existing antibiotics, then why do we not just
discover or create new antibiotics? There are several problems with this approach.
First, many bacterial species now have extensively drug-resistant (XDR) or even
pan-drug-resistant (PDR) strains that are resistant to most or all known antibiotics
that they were previously susceptible to. These strains are causing considerable
difficulties in hospitals and the cost of treating them is far higher than for non-resistant
strains.
The development of antibiotics has slowed markedly in the 21st century. From 2008
to 2012, just four new antibiotics were approved for the US market, compared with 16
during the period 1983–1987. In fact, no new antibiotics have been discovered for a
class of bacteria called Gram-negative bacteria for 40 years. This is due to
a mixture of scientific, economic and regulatory reasons.

39. ▪Scientific causes: More commonly found antibiotics have mostly been discovered
already. They tend to crop up repeatedly when researchers are screening for drugs,
while new drugs are proving increasingly elusive. In addition, some potential new
antibiotics cannot be used, for example due to their toxicity.
▪Economic causes for producers: Antibiotics are generally prescribed for short periods
of time. This makes them much less profitable than drugs that the patient has to take
for the rest of their life, so pharmaceutical companies have less of an incentive to
invest millions into antibiotic research.
▪Regulatory causes: The hurdles that antibiotics have to clear tobe licenced for human
use have been getting higher. This means that companies have to invest more money
before seeing any return at all, and the risk of the drug not being approved is higher.
Together, these factors go a long way towards explaining why antibiotic development
has been stalling, and why using the ones we do have wisely is such a crucial matter

40. Alternative to Antibiotics
Scientists have speculated what we could do if worst came to worst
and we had to make do without any antibiotics. Researchers are
exploring other possibilities.

41. Bacteriophages and phage therapy
Bacteriophages are viruses that infect bacteria – their name translates as ‘bacteria
eaters’. Until recently, they received little attention from Western doctors – widely
available and effective antibiotics were much easier to use. In the former Soviet
Union, however, access to cutting-edge antibiotics was severely limited, and some
scientists used bacteriophages to treat many infections
.
Voluntarily letting bacterial viruses into our body is an unpleasant idea for many of
us, even if they kill pathogenic bacteria – this in part is why phage therapy has
been slow to take off in Western countries. With antibiotic resistance becoming an
ever more real issue, though, the US National Institute of Allergy and Infectious
Diseases is planning large-scale clinical trials of phage-based
therapies

42. Phage therapy: a bacteriophage is shown injecting its genome into the bacterium.

43. One advantage of bacteriophages over antibiotics is their availability: thought to be
the most abundant organisms on Earth, they are so diverse that no two identical
phages have ever been found. This means that the bacterial hosts and phage
co-evolve so when bacteria become resistant to a phage the phage will
often evolve to re-infect it. Because of this, phage are described as ‘bacteria
specific ‘
Of course, there are difficulties that need to be addressed before
bacteriophages can progress beyond the trial phase. For example, regulating such
a rapidly evolving drug will be a formidable challenge. And because the methods
are not novel, pharmaceutical companies are unlikely to be able to register patents,
cutting into their profits.
While phage therapy is unlikely to completely replace antibiotics, scientists can
imagine it being used on topical infections as an alternative therapy in cases where
antibiotics have proved ineffective

44. Antivirulence drugs
Traditional antibiotics inhibit the growth of bacteria or kill them outright. A novel
class of drugs called antivirulence drugs instead disables the specific proteins the
bacterium uses to attach to our cells, preventing it from establishing an infection.
Because antivirulence drugs ‘disarm’ rather than kill bacteria, they may not drive
development of antibiotic resistance because susceptible organisms can still pass
on their genetic material: resistance is not selected for. A study of antivirulence drugs
has shown that drug-resistant bacterial strains will not come to dominate susceptible
ones; this means that the drug can remain effective.
An antivirulence drug has recently been found to be effective against MRSA
infections in mice. MRSA is a dangerous strain that causes infections in hospitals,
care homes and even in gym locker rooms, so to find a drug that is effective
against this bacterium is a positive step forward.

45. Antivirulence drugs to target bacterial secretion systems

46. Bacteriocins
Bacteriocins are proteins produced by bacteria that are toxic to similar or
closely related bacteria. Essentially, they are narrow spectrum antibiotics that
bacteria produce to eliminate competitors. Bacteriocins that attack pathogens
and are produced by bacteria that are harmless to us would make ideal
antibiotics.
A number of bacteriocins are now being studied for potential use as
antibacterial medication. They are also increasingly used to prevent the
growth of dangerous bacteria in food, extending shelf life
and delaying food spoilage. One example is nisin, which is approved
and used in food production and is known as E2.

47. Off-target consequences of antibiotics, bacteriocins and phage on microbial communities. As well as killing its target the
antibiotic kills the surroundingmicrobial community. Incontrast, bacteriocins and phage do not alter the surrounding microbial
community but kill the specific target only

48. Why should I care about antibiotics resistance?
Antibiotic resistance can affect any person, at any stage of life. People
receiving health care or those with weakened immune systems are often
at higher risk for getting an infection.
Antibiotic resistance jeopardizes advancements in modern health care
that we have come to rely on, such as joint replacements, organ
transplants, and cancer therapy. These procedures have a significant risk
of infection, and patients won’t be able to receive them if effective
antibiotics are not available.
Aside from healthcare, antibiotic resistance also impacts veterinary and
agriculture industries.

49. Prevention and control
Antibiotic resistance is accelerated by the misuse and overuse
of antibiotics, as well as poor infection prevention and control.
Steps can be taken at all levels of society to reduce the impact
and limit the spread of resistance.

50. Individuals
● To prevent and control the spread of antibiotic resistance, individuals can:
● 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, practising safer sex, and keeping
vaccinations up to date.
● Prepare food hygienically, following the WHO Five Keys to Safer Food (keep
clean, separate raw and cooked, cook thoroughly, keep food at safe temperatures,
use safe water and raw materials) and choose foods that have been produced
without the use of antibiotics for growth promotion or disease prevention in healthy
animals.

51. Policy makers
To prevent and control the spread of antibiotic resistance, policy
makers can:
● Ensure a robust national action plan to tackle antibiotic resistance
is in place.
● Improve surveillance of antibiotic-resistant infections.
● Strengthen policies, programmes, and implementation 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.

52. Health professionals
● To prevent and control the spread of antibiotic resistance, health
professionals can:
● 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 example,
vaccination, hand washing, safer sex, and covering nose and mouth
when sneezing).

53. Health care Industry
To prevent and control the spread of antibiotic resistance, the health
industry can:
Invest in research and development of new antibiotics, vaccines,
diagnostics and other tools.

54. 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 diseases 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.

55. Recent Developments
While there are some new antibiotics in development, none of
them are expected to be effective against the most dangerous
forms of antibiotic-resistant bacteria.
Given the ease and frequency with which people now travel,
antibiotic resistance is a global problem, requiring efforts from
all nations and many sectors.

56. Impact
When infections can no longer be treated by first-line antibiotics,
more expensive medicines must be used. A longer duration of
illness and treatment, often in hospitals, increases health care
costs as well as the economic burden on families and societies.
Antibiotic resistance is putting the achievements of modern
medicine at risk. Organ transplantations, chemotherapy and
surgeries such as caesarean sections become much more
dangerous without effective antibiotics for the prevention and
treatment of infections.

57. References
https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance#:~
:text=Introduction,animals%2C%20become%20antibiotic%2Dresistant.
https://www.researchgate.net/publication/281405283_Antibiotics_Introducti
on_to_Classification
https://medium.com/i3hs-hub/antibiotics-and-you-an-introduction-to-antibi
otic-resistant-infections-54ff9cc3354d
https://infectioncontrol.tips/2015/11/18/6-factors-that-have-caused-antib
iotic-resistance/
https://www.researchgate.net/figure/Schematic-diagram-highlighting-the-an
tibiotic-resistance-mechanisms-utilized-by-bacteria_fig1_323583521

58. https://www.britannica.com/science/bacteria/Evolution-of-bac
teria
https://en.wikipedia.org/wiki/Earliest_known_life_forms
https://www.dovepress.com/staphyloxanthin-a-potential-target
-for-antivirulence-therapy-peer-reviewed-fulltext-article-ID
R
Oxford Acadamic Journals
ResearchGate Articles
Images-dreamtime. com,shutter lock, pinterest and
wallpaperscave. com/bacteria wallpapers

59. Thank you