welcome to another MedCram lecture we're going to talk about Sept raw or
trimethoprim sulfamethoxazole this antibiotic is also
known as Code triazole but the first thing that we have to know before we
understand trimethoprim sulfamethoxazole as an antibiotic is one of the pathways
to making this item down here which is thymidine now as you know thymidine is
an essential part of DNA it is the T in the genetic code and how it is
synthesized is very important because without this synthesis you can't have
life so let's take a look at that here for a second we've got this synthesis
starts off with Tara Dean and P ABA which is this molecule here now P ABA
stands for para amino benzoic acid and these two come together with the help of
this enzyme called die hydro Tara weight synthase to make a new substance called
dihydrotestosterone folic acid dihydrofolate acid then under the
enzymatic action of dihydrofolate reductase makes tetrahydrofolate acid
which then finally goes the thymidine now in bacteria if we can inhibit these
two enzymes here in green then perhaps the bacterial will cease making
thymidine and the bacteria will die and that's exactly what this antibiotic does
there's trimethoprim which is the first component and then sulfamethoxazole now
the sulfamethoxazole actually works here at the first enzyme so it blocks it and
the reason why it blocks it is that sulfamethoxazole is a similar molecule
to the para amino benzoic acid and so this enzyme the dye hydro 408 synthase
mistakes this sulfamethoxazole for a PABA
PA ba and therefore it shuts it down now sometimes some of it gets through or in
other instances as we'll talk about there may be a mutation and that's when
the other one comes in or the trimethoprim
trimethoprim which works here at the dihydrofolate reductase step also blocks
it so if the bacteria is susceptible at both areas you're gonna get synergistic
effect of this antibiotic however remember though that if there is a
resistance at just one of these it's still going to kill bacteria because all
it needs is just one of these enzymes but the fact that there are two
antibiotics in one makes it even more of a potent antibiotic now one of the
important things to know is that this version of dihydrofolate reductase
there's two different versions there's the version that's in bacteria and then
there's the version that is in human beings of course we're talking about the
bacterial enzyme that trimethoprim primarily hits it does hit a little bit
of the human enzyme so the effect is is that there will be a slight reduction in
thiamine but even more than that there will be a reduction in folic acid which
can be a problem as we'll talk about in a little bit so what are the bacterias
if you will or bacterial species that do try to counteract this trimethoprim by
having a mutation in the dihydrofolate reductase well some of the ones that you
may think about the big ones would be Enterococcus and Campylobacter okay and
then some of the bacteria that have resistance here in the dye hydro ferro a
synthase which is where sulfamethoxazole works would be a very important one
known as Pneumocystis Djurovic ii this is commonly seen in HIV and AIDS
patients in fact it's an aids-defining condition Pneumocystis Djurovic ii used
to be known as Pneumocystis Carini i and so this one can often have mutations
here in this dihedral tara weight synthase other mechanisms of resistance
to by method from sulfamethoxazole is the influx of this antibiotic inside the
cell the bacteria and the e flux obviously if
there is resistance to influx that's going to be a resistant we typically see
that in e.coli species if there's going to be resistance but then also we see it
in Pseudomonas that it actively pumps the trimethoprim outside of the cell so
that it is not as effective okay so to review this portion of it trimethoprim
sulfamethoxazole is a combination antibiotic it works in the metabolism of
folic acid and the creation of thymidine it works at two different positions and
bacteria can't have resistant mechanisms against it okay let's talk about the
type of bacteria that cetera is typically used against it's not
exclusive could be others but generally speaking where you might see this come
in so in terms of gram positives one of the things that we see often is mr sa
especially the community acquired mr sa or see mr sa obviously on a sensitivity
profile you'll see that it is sensitive to sept rub but it's not always the best
choice to give it as mono therapy but it can sometimes be added the other gram
positive or weakly gram positive that you might see is nocardia
so if you see nocardia think of cetera or trimethoprim sulfamethoxazole in
terms of gram negatives one that we typically see in intubated patients if
we're gonna see it it's rare usually in hospitalized patient this is called
steno Truffaut monas multi philia it's a mouthful but you can say it's tenet rofl
monas multi philia and this bacteria is usually only sensitive to either
levaquin or fluoroquinolones or this antibiotic which is cetera sometimes
it's also sensitive to tetracyclines however the biggest one the biggest
gram-negative that you'll see is those bacteria that cause UTIs and we'll talk
about why your Neri tract infections are so useful for
this and part of the reason I can tell you up front is because cetera is renal
e excreted and so it concentrates in all of the genital urinary tract organs so
whether it is the prostate or whether it is the seminal vesicles or whether it is
the bladder the urethra this has got an excellent gram-negative coverage
although we're starting to see about a 20% resistant in some areas to E coli as
we talked about earlier with that inhibition of influx of the antibiotic
into the cell the other one though that you should know about in terms of other
of course is Pneumocystis Djurovic e otherwise known as Pneumocystis Carini i
this is really important because in HIV patients or AIDS patients who have
Pneumocystis this is really the treatment of choice and as we'll talk
about later unfortunately it's in those HIV patients where you get the most
complications from this medication so you have to watch out for this to make
sure that doesn't happen this antibiotic is widely distributed so
it goes into the CSF it goes into the plasma it goes into the urine it does
follow first order kinetics and the half-life is approximately 10 to 12
hours so it's typically dosed at least twice a day and again the big thing here
is it is excreted in urine that's what makes it so good for the treatment of
UTIs okay let's quickly talk about the dosing sometimes this can be a little
bit confusing but there is what they call single strength double strength
suspension and IV and the way it typically is listed is that the
trimethoprim is listed first and then the sulfamethoxazole is listed second in
milligrams and in terms of how much of this you give so there's always together
it's always listed in milligrams of the trimethoprim so they'll always tell you
start cetera and do so many milligrams of the TMP and what you'll notice is
that the sulfamethoxazole is always five times that of the trimethoprim so you'll
always remember that the SMX or the sulfamethoxazole is always five times
more than the trimethoprim and so the single strength is the 80 over 400 the
double strength of course is twice that now the liquid suspension is in 40 over
two hundred and five MLS so you just put that per teaspoon and then the
intravenous is actually the same concentration here except it is 80 and
400 in five MLS which if you do it per ml is simply that divided by five and
you'll see here that we have 16 over 80 so in all of these cases the
sulfamethoxazole is always 5 times more than the trimethoprim and what they will
typically do is they'll tell you how many milligrams of trimethoprim per day
let me say that again how many milligrams of trimethoprim per day you
need for a specific condition and then it's up to you to divide all of this
into bi ddosing or tid dosing okay so if they were to say that for a specific
infection that you needed to have oh let's say 320 milligrams of trimethoprim
per day you would simply say okay we need 320 we're gonna give it B ID that
would be half of 320 which would be 160 160 milligrams then of the
double-strength tablet to be given B ID okay so that can sometimes be a little
confusing because a lot of moving parts there but just remember this correlation
between the trimethoprim the sulfamethoxazole and the fact that
they'll give you the total daily dose and we will join you for the next video
when we talk about dosing and adverse reactions thanks for joining us