By Adem Lewis / in , , /

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

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