Today, we will talk about
antibiotics or antimicrobial drugs
There is a very important term
called: antimicrobial drugs.
Antimicrobial drugs can be
either extracted from living
organisms that release
products or crude extract
then we can use it as a
drug for killing bacteria
or such drugs can be synthetically
prepared in pharmaceutical companies
The drugs prepared from substances
produced by living organisms are called:
while the ones prepared
synthetically are called:
So there is a difference between
chemotherapy and antibiotics.
Antibiotics are extracted from fungus
or bacteria, any living organisms
For example, penicillin is produced by
fungus, so it is considered an antibiotic
Polymyxin is extracted from bacteria
Bacitracin is extracted from bacteria
so they are considered
antibiotics, since
both bacteria and fungus
are living organisms
So, in brief, antimicrobial drugs are divided
into antibiotics and chemotherapeutics
Antimicrobial drugs
can be Broadspectrum antibiotics where
they act on a wide group of bacteria
including gram positive, gram
negative and acid-fast bacteria
They act on a wide group of bacteria
Another type can only act
on gram positive or gram
negative bacteria, so
they have a limited spectrum
Those two types are very important.
Another type
kills bacteria. It is called: Cidal
which then becomes Bacteriocidal drug
If the drug prohibits
the bacterial growth,
preventing its replication,
then it is called:
bacteriostatic
So now we have cidal which kills bacteria,
and static which prohibits its growth
Broadspectrum acts on a large group
Limited spectrum works on specific groups,
either gram positive or gram negative
Antibiotics and chemotherapeutics
belong to the antimicrobial drugs
Antibiotics are extracted from living
organisms like bacteria and fungus
Chemotherapeutics are prepared
synthetically in laboratories
Alright, let's move on to
the drugs which act on microbes
Here I will draw the bacterial cell
There we have a bacterial cell wall
then the cytoplasmic membrane with its
invaginations that are called mesosomes
Inside
the cytoplasm, we have one
chromosome folded on itself
it is called a nuclear body
then you can see
This is the nuclear body
and this is the cytoplasmic
membrane which encloses cytoplasm
There is quite a significant difference
between Eukaryotic and Prokaryotic cells
Prokaryotic cells has 70S ribosomes
with 30S and 50S subunits
but is humans ribosomes are usually 80S
with two subunits
40S and 60S, alright?
So if we need to stop the action of
ribosomes to prevent protein synthesis
we can destroy the 70S of the bacteria
because if we destroy the 80S type, human
ribosomes will be badly affected
Now, the bacterial cell wall
is made of peptidoglycans
and teichoic acid
Peptidogylcans are made up
of n-acetyl muramic acid
and n-acetyl glucosamine
both compounds are
attached to each other by
triphosphorylation; forming
a very rigid cell wall
Its cell wall is rigid
because the prokaryotic cell
lives independently, so
it must protect itself
But the Eukaryotic cells live
in groups supporting each other
Therefore, the bacterial
cell wall is a very
important component which
prevents the cell's lysis
Alright
Antimicrobial drugs act on
the bacterial cell wall
such drugs can be either
antibiotics or chemotherapeutics
The most important drug is Penicillin
beta lactam groups
This is its structure
Penicillin along with its different types
All of those types
prevent the triphosphorylation
of n-acetyl muramic
acid and n-acetyl
glucosamine, so the cell wall
becomes fragile and the cytoplasm
leaves the cell by osmosis
along with all the cell contents
Therefore, this drug is bactericidal,
it acts on the cell wall
Ok, let's re-draw the cell wall
Fine
Another drug that acts on the cell wall is
it acts on the cell wall
What to use penicillin and
when to use vancomycin?
Staphylococcus bacteria is MRSA type
MRSA means
It resists the strongest
type of penicillin which
is methicillin or beta
lactam group in general
that is why we administer
vancomycin in such cases
Another type of drug is cephalosporins
or
There are a lot of
cephalosporin generations
Such drugs basically act on cell wall
Those drugs act on bacterial
cell wall or peptidoglycans,
such drug group is the best treatment
for gram positive bacteria
as the bacterial cell has a
lot of exposed peptidoglycans
but the gram negative bacteria have a
lipopolysaccharide layer covering their cell
wall so it is not preferred to use drugs
which act on cell wall to eradicate them
The cytoplasmic membrane is responsible
for selective permeability
it controls the entry and exit of molecules
into and out of the bacterial cell
We can use bactericidal to
disrupt the cytoplasmic membrane
Polymyxin acts on the bacterial
cytoplasmic membrane
this drug is toxic so it is used
as a topical treatment like creams
Polymyxin is an antibiotic since
it is extracted from bacteria
it can also kill other bacteria,
so it is bactericidal
Alright?
Most of the antifungal drugs act on the
cytoplasmic membrane of fungi, not bacteria
Why fungi? 
As here we have ergosterol
which is the target of the antifungal drugs,
by disruption of the cytoplasmic membrane
For example:
Amphotericin which acts on the
cytoplasmic membrane of the cell wall
Nystatin is another example
and Griseofulvin
Those drugs are antifungal, they act on
the cytoplasmic membrane of the cell
leading to its disruption
as there is no selective
permeability so any molecule
can enter or leave the cell
Alright
Nuclear bodies synthesise mRNA
This nuclear body is actually DNA.
It synthesises mRNA which
will then be translated by 70S
ribosomes (30S & 70S subunits)
to stop protein synthesis
This means that such
drugs stop the growth of
bacteria, so they are
bacteriostatic not bactericidal
For example:
Quinolone, tetracycline and chloramphenicol
Such drugs prohibit protein
synthesis, so they are static
Alright
Let's move on to the DNA, to
prevent DNA from synthesizing mRNA
some drugs must act of it
drugs can act of RNA itself
So, the nucleic acid, which is
composed of DNA and RNA, has
certain drugs acting on its
DNA & others act on its RNA
Rifampicin acts on RNA
while quinolones group acts on DNA
So, quinolones were mistakenly written
here, they should be macrolides
Those are the drugs which
act here and there
As you can see, each drug acts
on a certain layer of the cell
So, what does the bacteria need?
Bacteria needs to synthesise folic acid
as this is the first element
needed for protein synthesis
To synthesise folic acid
it needs
The cell takes in para aminobenzoic acid
which will be converted to folic
acid to be used in protein synthesis
So instead of growing the
bacteria in a medium containing
para aminobenzoic acid, we
change it for sulfonamides
so that they cause
competitive inhibition of
folic acid formation once they enter the
cell, so this is a bacteriostatic drug
You need to have your own copy of
this drawing and study it regularly
So, which drugs act on the cell wall?
Bactericidal
What about cytoplasmic membrane?
Bactericidal, too.
Other types of drugs prevent
the growth of bacteria
by inhibiting 70S ribosomes
(30S and 50S subunits)
By the way each subunit has
certain drugs, but I will not
discuss them, they are more
important to pharmacy students
such drugs are usually
bacteriostatic but there
are bactericidal drugs
among them as well
The drugs that inhibit bacterial growth can
also act on DNA or RNA (nucleic acids)
Rifampicin acts on RNA while
quinolones act on DNA.
The drugs which act of cytoplasmic
membrane are usually toxic
Antifungal drugs only work on
ergosterols found in fungus
like Nystatin and Griseofulvin
Competitive inhibition occurs
when we add sulfonamides
instead of PABA to prevent
formation of folic acid
Trimethoprim is also used for inhibition
What are the complications
of antimicrobial therapy?
Antibiotics result in some
complications despite their benefits
I will explain it to you in an easy way
2 prolonged
2 early
1 toxicity
1 hypersensitivity
So there are 6 complications
The first two points result from administering
the drug for a long period of time
Drugs actually kill pathogenic and
non-pathogenic (commensal) organisms
The commensals represent
natural immunity which
defend the body against
harmful, disease-causing, bacteria
So, firstly, prolonged
use of drugs kills the
commensal bacteria so the
innate immunity weakens
and leads to resistance
of bacteria to drugs
You know, when we use DDT to
kill cockroaches for a long
time, cockroaches start feeding
on DDT and ask for more!
It is because their bodies
became resistant to such drug
as result of its prolonged use
We will discuss the resistance
point further more later on.
The early use of drugs without diagnosis
For example, if someone has
Typhoid, among the symptoms
of this disease is feeling
warm and having diarrhea
If the doctor fails to diagnose
the patient properly, they
will administer antibiotics like penicillin
which will kill some bacteria, but
actually there was no complete
eradication of bacteria
as the proper type of
antibiotics wasn't used
so early use without
diagnosis is very dangerous
Early use can lead to
inhibition of immunity
resulting in infections to the patient
as the immunity weakens whether it is
acquired, humoral or cell mediated
due to disturbance caused by
antibiotics to the immune cells
So, the prolonged use kills the commensals
leading to colonization which
results in the formation
of ulcers in the mouth, diarrhea
and other complications
then the microbe becomes
resistant to the drug
The early use masks the
symptoms making it confusing
to diagnose the patient due
to alteration in symptoms
So if one of your patients
doesn't feel well after
antibiotics administration,
let them stop using it
until the sensitivity
symptoms disappear then start
administering the proper
type of antibiotics
Early use can also weaken the immunity
making the patient vulnerable to infections
Let's move on to the toxicity
Chloramphenicol cause
aplastic anaemia, we used to
administer it a lot to
patients, now it is prohibited
It leads to bone marrow depression anaemia
it prohibits the activity
of the bone marrow
Tetracycline causes
It acts on the auditory 8th nerve. The
patient feels a blow in their ear
that is because the tetracycline
and streptomycins are one
thing, they both lead to 8th
nerve paralysis and deafness
Tetracyclines stain the teeth
permanently
Fine
There are many more drugs
that lead to toxicity
The first drug is
and others
for teeth stain
Penicillin is toxic too
and there are nephrotoxic
and hepatotoxic drugs
so take care
Penicillin causes type 1 hypersensitivity
leading to anaphylaxis
and atopic diseases. Those are all the
complications of antibiotics
What if the antibiotic
can't eradicate the bacteria
in the patient's body?
In this case, we administer
combined antibiotics
or
The combined treatment is classified
into synergism and antagonism
Synergism means that when
two drugs are combined
together, their effect is
higher that each drug solely
Understood?
Using the two drugs together is more
effective than each drug alone.
Antagonism means that each drug alone
is more effective than both together
So I won't definitely administer
synergistic drugs to patients
Alright
When to administer combined antibiotics?
Combined antibiotics are used
in surgical operations where
there are many types of bacteria
like in colon surgeries
or bladder surgeries
There is a lot of bacteria
in the groin and colon areas
So we must administer broadspectrum
antibiotics in colon or GIT surgeries
Ok
If someone had an accident, their
body will be covered with bacteria
from street so we must administer
combined antibiotics without diagnosis
Just administer any broadspectrum
antibiotic without thinking about it
Why do some antibiotics
fail to treat patients?
1- Wrong Dose
or weak one
The second thing is discontinuation
patients take in drugs every 24 hrs
instead of 12 hrs and skip some days
so the drug fails to treat them
3- Penetration of the drug
4- Choice of drug (gram
positive or gram negative)
Administering the drug
empirically, like in accidents
Alright
What else? Resistance to the antibiotic
What is resistance?
Some bacteria resist the
action of penicillin
(beta lactam) so they
release beta lactamase
which then makes the beta lactam useless
In this case, we can either administer
methicillin as it is beta lactamase resistant
Can you remember this?
We can also administer amoxicillin
along with clavulanic acid
Clavulanic acid prohibits
the action of beta
lactamase, so amoxicillin
acts by forming umbrella
on the beta lactamase released by bacteria
so that the drug can work properly
Fine
What if a patient with
gonorrhea disease or any
injury uses antibiotics
but never heals?
And the doctor refuses to
do analysis to prevent
the patient from paying too
much, is this logical?
Once you find no response for two,
three or four days, you must carry out
What is this?
Bring this media plate
blood agar, McConkey or whatever
then
take a sample of the
organism from the patient
for example if the patient has pus,
take a sample of it and plant it
or extract the urine microbes
or any discharge's microbes then plant them
as you can see here on the medium plate
This way no separate
colonies will be formed
only heavy growth of bacteria
In the clinic, you can find
discs
You know when you use the hole punch,
you get small circular pieces of paper
we use those pieces here
one piece would hold
amoxicillin, another holds
methicillin, third one carries
sulfur, the fourth
holds chloramphenicol, the fifth holds
tetracycline and so on
Leave this bacterial culture
to grow and then find
where the microbe has
actually grown the next day
Around the antibiotic disc
the microbe didn't grow
neither did it grow here
as you can see
same with this disc
same with this disc
but bacteria has grown here and there
So now see which antibiotic
these discs represent
this antibiotic is +++, meaning that it is
the most suitable for patient treatment
The inhibition of this antibiotic
prevented the bacterial growth effectively
leaving a large diameter circle
free of bacteria around its disc
This disc is followed by
this one, then this one
So, the patient can take
this OR this OR this.
Why do we have options?
Maybe the +++ type
is too expensive for the patient, so they can
but ++ type or + type as they are cheaper
This is the antibiotic sensitivity test
or disc diffusion method
Alright?
Enough with the names.
This is the antibiotic sensitivity test
that is carried out in the laboratory
to define the proper drug to
be administered to the patient
Alright. Let's learn more
about the resistance
Microbes can release drug
antagonists like beta lactamase
What else?
The bacterial cell can change the
target on which the drug acts
This changes its metabolism. For
example, I want to go to Al Maadi
My son, Ahmed, would tell me
to use Salah Salem Road
whenever I use this road and reach Darrasa,
people would gather around me and hit me
This way I won't ever reach Al Maadi!
But if I changed my route path,
I will reach. So the bacteria
does the same thing, it
changes its metabolic pathway
This is the change in the metabolic pathway
In some bacterial cells,
you can find plasmid
Plasmid is made up of DNA
along with some genes, one of those
genes can be resistant to certain drugs
This plasmid can replicate and
move on to another bacterial cell
So now the bacteria that used
to be killed with antibiotics
has become resistant after
the plasmid transfer
Why did this happen? Due to
conjugation, the bacterial pilli
transferred the resistant genes
from this cell to the other
Alright? This point belongs to genetics
If you remember, in the Bacteriophage
session, we said that the temperate
phage attacks the bacterial chromosome
which contains resistant gene
and moves it outside the
cell, so there you have
the resistant gene along
with the bacteriophage
It infects another bacterial cell.
This is called
I hope you have understood this
quite difficult yet nice session
