00:01
Now our cell wall synthesis inhibitors have
different subtypes and I mentioned them
before. Let's start off with the
penicillins.
00:09
We have many different subcategories of the
penicillins.
00:12
There are the natural ones, the beta
lactamase resistance ones, the amino and the
carboxy penicillins and then there's the
ureido carboxy penicillins and the ureido
penicillins. Now, penicillin is one of our
oldest drugs.
00:25
The discovery of penicillin was one of the
most significant medical breakthroughs of the
20th century. In 1928, Dr.
00:31
Alexander Fleming observed a mold,
Penicillium notatum, contaminating his
Petri dishes, which inhibited the growth of
Staphylococcus aureus.
00:41
He could not identify the antibacterial
element due to resource constraints and
his findings initially attracted little
attention.
00:49
Ten years later, in 1938, Dr.
00:52
Howard Florey at Oxford University saw
potential in Fleming's work
and successfully isolated and purified
penicillin from the mold.
01:02
By 1940, Florey's experiments on mice
infected with streptococcus showed
that while untreated mice died, those
treated with penicillin survived, marking a
significant milestone.
01:14
Between 1941 and 1942, mass production of
penicillin was realized.
01:19
In 1942, the first human patient was
successfully treated with
penicillin. During World War II, from 1942
to 1945,
penicillin was initially reserved for Allied
soldiers, significantly reducing the death
rate from battle wounds and other
infections, including bacterial pneumonia.
01:39
By 1945, it was released to the public as
American companies were
producing it in large quantities, and it was
marketed as a treatment for various
infections, including gonorrhea.
01:51
In 1945, the Nobel Prize was awarded to
Fleming, Florey, and
Chain for penicillin, with Fleming warning
of possible bacterial resistance.
02:01
Dr. Norman Heatley, also pivotal in its
development, was later acknowledged by
Oxford with an honorary doctorate of
medicine.
02:09
There are several different types of
penicillins.
02:12
The natural penicillin are just what they
sound like, they come from the
penicillium mold.
02:19
Penicillin G is the most commonly known but
there's many different types, there's K, N,
V, so the narrow spectrum penicillin G is
used mostly
in strep throat and necrotizing
enterocolitis.
02:34
These agents are very commonly used in
syphilis and
leptospirosis and they are of course used in
gonorrhea but not so much anymore.
02:43
This is an old drug and it tended to focus
mostly on gram positive organisms and it
was given intravenously or intramuscularly.
02:51
Nowadays, we have newer agents that have
mostly replaced penicillin G but it's still
used quite a bit in certain areas and in
certain countries.
03:01
Penicillin V on the other hand is used a
little bit more commonly in strep
throat. We also use it in otitis media
especially in children.
03:09
We use it sometimes in cellulitis and of
course we use it to decrease the risk of
rheumatic fever. We do use it in splenectomy
patients because splenectomy
patients are more prone to certain types of
bacterial infections.
03:24
One of the nice things about penicillin V
compared to G is that it's acid stable.
03:28
That means it can survive in the gut and
therefore can be given orally.
03:34
The next category consists of beta-lactamase
resistant penicillins.
03:39
Now they tend to be narrow spectrum as well.
03:41
They can include methicillin or oxacillin.
03:44
I've highlighted two of them that are most
commonly used in bold face.
03:48
Cloxacillin is something I literally just
prescribed a few days ago.
03:53
It's used in skin infections cellulitis,
impetigo.
03:56
It's also used in some pneumonias, septic
arthritis and otitis.
04:02
Now it is safe in pregnancies so we tend to
use it a lot in our pregnant patients
particularly those with skin infections or
with otitis infections.
04:11
Staph that produce beta-lactamase can be
treated with cloxacillin.
04:16
Now there is a long R chain that is present
in cloxacillin.
04:21
This prevents the beta lactamase from
actually binding to it that's why it's so
effective even in patients who have beta
lactamase producing bacteria.
04:31
Methicillin is another drug in this
category.
04:35
It isn't really used as much anymore.
04:38
It is important because we know about a lot
of
resistance to this drug so we have typically
methicillin resistant staphylococcal
aureus. Now MRSA as its commonly known is a
real problem in our
hospitals. So I mention methicillin not
because we use it but because we shouldn't
use. It is also linked to interstitial
nephritis that's an important
exam question for some of you but as I've
said again, we don't really use this
medication anymore. Another medication that
we use in this class is
nafcillin. It is associated with
neutropenia, I won't really go into too much
detail other than the fact that nafcillin
neutropenia, there's a
memory cue their N and N and I have seen
that in exam questions as
well. Okay, let's move on to the amino
penicillins.
05:29
Amino penicillin includes ampicillin and
amoxicillin and I bet that you
have probably been on one of these
antibiotics.
05:38
They have a wide spectrum of activity but
they can still be susceptible
to the beta lactamases.
05:45
They can be oral or they can be intravenous
or they can be intramuscular.
05:50
We use these drugs in various infections
that includes bacterial
meningitis, endocarditis, GI infections like
salmonella.
06:00
They can also be used in genitourinary
infections and they can often be used in
catheter-based infections.
06:07
For example, I had a patient in the nursing
home that I see that I round in
had a catheter-based infection of his
indwelling urinary catheter.
06:16
We use a combination of ampicillin and
gentamycin to treat the infection so it's a
very, very, commonly used class of drugs.
06:24
We also use ampicillin and amoxicillin in
bacterial endocarditis
prophylaxis. What is bacterial endocarditis
prophylaxis?
If you have an implanted cardiac valve,
let's say an artificial aortic valve
and then you go for a dental surgery.
06:41
You need to have antibiotics to protect the
valve from becoming infected
so we use a ampicillin as a gram taken a
half hour before the
procedure and that usually protects that
patient from getting infected from his dental
surgery. Ampicillin can also be enhanced
with
additional agent so amoxicillin or
ampicillin can be added with
clavulanate to protect it from the effects
of the
beta-lactamase and also give it added
synergistic activity.
07:14
In enterococcal infections we use
aminoglycosides in combination
with the ampicillin or the amoxicillin.
07:22
As I've mentioned before, ampicillin
gentamycin is a very common type of
regimen that we use for complicated
infections.
07:31
Next, we have the carboxy penicillin these
include like ticarcillin.
07:35
Now ticarcillin is generally considered to
be more of an intensive care unit
drug. It has strong activity against gram
negative organisms so we will
sometimes use carboxypenicillins against
pseudomonas and maltophilia type infection.
07:51
We will also use it in combination with the
aminoglycosides.
07:56
We almost always take these medications in
combination with
clavulanate so for example we'll have
ticarcillin clavulanate as a combination
product because we want to protect against
resistance.
08:11
Finally, we have the ureidopenicillins.
08:14
The ureidopenicillins can include drugs like
pipercillin.
08:18
Pipercillin Is also an intensive care unit
kind of a drug.
08:21
It’s a very broad-spectrum agent it has very
good gram-negative coverage but it also
has some good gram-positive coverage as
well.
08:29
Once again, we like to pair this with a
beta-lactamase inhibitor.
08:33
In the case of piperacillin, we combine it
with tazobactam.
08:38
Pseudomonas is a problematic agent that we
sometimes see in wet
infections, so we often call this the
sneaker shoe kind of infection, it smells
like sneaker shoes just that horrible kind
of a stench.
08:52
We see that sometimes in intubated patients
in the intensive care unit
complicated infections involving areas like
mucosa,
so it's typically thought of as a wet
infection and piperacillin is often use to
treat it. Now, one of the problems of
piperacillin of course is that
it lacks strong activity against staph
aureus so that can be a problem when
you are trying to choose a medication or an
antibiotic regimen and you don't know what
the cause of the organism is or you don't
have a good suspicion.
09:24
We also use piperacillin tazobactam in
neutropenic sepsis so like I
said it's a very good antibiotic in very
sick patients.
09:34
Mezlocillin is another one that I think is
important to remember because it is excreted
by the liver. Now why is that important?
Why do we want a drug that's actually
excreted by the liver, and why would that
give us any kind of advantage?
Well, think about this, if you have a
biliary tract infection in the liver it makes
sense to give a drug that's concentrated in
the liver, that's where we use this
medication.