Brown welcome to another MedCram lecture we're going to talk about
penicillins today and don't worry you're not going to be asked to memorize this
structure for penicillin but we're going to talk about the evolution of the
penicillin molecule in terms of the drug market and the different types of
penicillins that are out there and why there are different types of penicillin
I think the story is instructive in terms of the different types of
penicillin on the market today and what they're useful for the first thing I
wanted to show you though is this area right here in the middle and that is the
site of the penicillin ACE action break in the beta-lactam ring we'll talk about
that in a little bit so first of all let's start with penicillin and we'll
represent that as AP here now penicillin was invented back in the 1940s one of
the very first antibiotics used worked really well on kind of the uses that
they had for at the time and the type of uses that they had for it if you can
imagine this bacteria with all of the wounds during the war they were looking
for an antibiotic that was good for skin flora in other words gram-positive
organisms so really didn't work that well for gram negative so gram negatives
weren't really covered so penicillin did a really good job at attacking the
bacteria through these penicillin binding proteins that were on the
surface of the bacteria problem was these bacteria eventually became
resistant to it and they form this thing called penicillin ace which basically
destroyed the penicillin and prevented it from doing its job so it basically
formed resistance so as a result of that the next thing that came up with was a
what they call the semi synthetic
penicillins and so you'll notice that these have the abbreviation M O and M
stands for methicillin-resistant and n stands for naphthalene all three of
these were able to attack this bacteria that was still making the penicillin ace
and they did it at the same binding protein ok the penicillin binding
protein but when these peles penicillin ace molecules that were made by the
bacteria tried to attack it they couldn't and so we successfully were
able to overcome one generation of resistance by using these semi synthetic
penicillins methicillin oxacillin naphthalene and these medications here
are probably the best medications for staph so if this bacteria that we're
talking about is a skin flora and its staff then the best ones are these semi
synthetic penicillins still even to this day ok so the next problem was so the
skin floor works well we got these medications that work really well but
they don't cover the gram negatives we need to cover gram negatives and so a
couple of things happened they came up with different types of penicillins that
would cover that and so there's really two types of bacteria afterwards that
were looked at of course the skin flora was still something that needed to be
covered so skin floor which was grand positive so put your skin gram-positive
and then there was some you know the group of bacteria that had gram
negatives that were the let's say the easy ones the easy gram negative select
the eco lies in the urine and the eco lies in the stool and then there were
the gram negative hards okay so these are the resistant gram negatives like
and the big one here is Pseudomonas and so at first they came up with an abaya
is to cover these grand positives and some of these easier gram negatives and
those are known as the amino penicillins so things like ampicillin or the oral
form amoxicillin and those again killed really well the ones that they came up
with for these really difficult ones like the Pseudomonas was called extended
spectrum penicillins and which ones are we talking about
there we're talking about pepra Silla and Teicher Celyn so I'll just say pip
and Tyco are Celyn and those did a good job of attacking this with the
Pseudomonas in it but then a problem came these bacteria started making
something called beta lactam aces and it started breaking up the antibiotics in
that square I was showing it at the beginning and so these beta lactam aces
would attack here and there would be resistance okay so we had a real problem
so what we did was we started adding these beta lactamase inhibitors so when
we took for instance ampicillin and
coupled it with seoul back down to make unison now we could attack that bug
because in addition to that it would also attack the beta lactamase and take
it out also we would take amoxicillin and couple that with clavulanic acid and
we would come up with augmentin okay and that would do the same thing we'll be
able to attack that bacteria because we would get rid of the beta lactamase
similarly down here we would take pepper Siwan and we would couple it with Tazo
back down and we would get a medication called
zosyn and we could take Tyco Ursuline and couple that with clavulanic acid and
come up with the medication ty Menton and again that would attack the bacteria
like it normally would and these would attack the beta lactamase to prevent the
beta lactamase from eating the beta-lactam ring of the pepper cylinder
the Taser back down so notice how many different medications we have we have
regular penicillin we have methicillin which is good against mostly gram
positives but not a lot of gram negatives and especially staff oxacillin
and naphthalene are in that same category so naff would be the
appropriate choice in a sensitive staph aureus that's probably one of the best
medications you can give ampicillin sole backed am is great for most gram
positives and a few easy gram negatives amoxicillin with clavulanic acid
augmentin also the same the other option is zosyn or pip resilient azo backed em
which has Pseudomonas coverage along with time ensign which is thai crystal
and clavulanic acid which also has good sunomono coverage so depending on what
your spectrum is that you want to use you can use these different penicillins
now something in the last 10 or 20 years occurred where we had a big problem and
the big problem is that staph aureus which will put up into this area develop
something called mek a now what's MEK a mek a is a mutation that actually
changed the penicillin binding protein here so no longer would penicillin work
on staph aureus and no longer would methicillin oxacillin or naphthalene
work on staph aureus so this was known as
methicillin-resistant Staph aureus in other words the mek a gene made
M R s a methicillin-resistant Staph aureus so we had to come up with a
completely new way of attacking this organism because the actual binding site
itself had been changed and so the other medications that can be used if it's a
mild infection you can use things like clinda which it hits the 50s subunit of
the ribosome there cetera which actually hits folic acid and purine production
and then there's quinolones which can also hit it occasionally which has to do
a DNA gyrase but for the more severe infections the
way to go is Vanko ok Vanko which also works on the cell wall in a different
way you can use daptomycin or you can use luna solid Lynnae solid dap dough or
Vanko and so that is why we use vancomycin now in almost all
gram-positive infections that are possible acquired because of the high
risk of mrs a infections so we talked about a lot of things here this is the
story of penicillin very briefly I would say that in terms of side effects you
have to worry about cross reaction with penicillin allergies probably the one
that has the least amount are the newer ones like zosyn and tai Menton however
the things that you have to be concerned about with zosyn are low platelets if
you see low platelets and so amaz Osen just be aware of that so the number one
drug to use in a patient with M s si or methicillin sensitive staph aureus is
nafs Ilyn we like to say that nafs Ilyn gets up in the morning to kill staph
aureus so if it's sensitive to it that's the best one to use if it's not
sensitive to it then you'll have em RSA then Vanko DAP do--and linezolid are
your choices hope this helps thanks for joining us
you