Sulfamethoxazole/Trimethoprim (Bactrim, Septra): Uses, Coverage, Dosage, UTI Treatment, Etc.

Sulfamethoxazole/Trimethoprim (Bactrim, Septra): Uses, Coverage, Dosage, UTI Treatment, Etc.

November 4, 2019 1 By Jose Scott


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