Voiceover: This is Charles Proburg.
Voiceover: And Morgan Theiss.
Voiceover: And we're going to talk on this video
about the treatment of active tuberculosis infection.
And I'll state the obvious up front,
which is the reason you want to treat somebody
with any infectious disease, in this case, tuberculosis,
is to prevent disability and death from the infection.
Another reason for treating infectious diseases,
especially important with TB is to reduce
the spread of infection to other individuals.
The good news about the treatment
of active TB infection is that we have
a number of drugs which have been developed
over time that are really quite effective
at treating the infection.
The bad news is that unlike many infectious diseases,
these drugs have to be given for a fairly
long period of time.
They usually have to be given in combination,
so you need multiple drugs to be effective
in treating and the other bad news is
that resistance among strains of tuberculosis
is becoming a problem globally
and we're going to talk about the treatment
of resistant organisms on another video
because it, in itself, is quite complicated,
but for the purpose of this video,
we're going to talk about the treatment
of active TB and we're going to make the infection
the most common variety.
The one that we're most likely to see
and want to treat and that's an individual
with pulmonary tuberculosis.
So, the first thing is, of course,
we have to diagnose the infection.
So, let's assume that we've done that.
We know that this person has active TB
caused by active TB in their lungs
and we want to initiate therapy.
For most individuals, the therapy begins
with a combination of four drugs.
This is assuming we don't know that this
is a resistant organism and the four drugs
that we start off with are ...
There's an acronym called RIPE. R-I-P-E.
Where the R stands for rifampin,
the I stands for isoniazid or INH,
the P stands for pyrazinamide or PZA,
and the E stands for Ethambutol.
And we treat the patient with all four drugs
right at the outset, with the reason for that
is anticipate to be for a two month period
and the reason for that is we want to blast the infection
and eliminate as many of the organisms as possible
as quickly as possible.
So, these are powerful anti-tuberculosis agents,
first line agents that are aimed to kill the TB
as quickly as possible over that two month period.
Voiceover: So, we're calling them bactericidal, right?
Voiceover: They're bactericidal antibiotics
that kill the TB.
We confirm that by doing cultures along the way,
but those are the antibiotics that we start with
and that's sort of the intensive phase of therapy,
that two month period.
Then, if all goes well, we back off to just two drugs
for the ensuing four months and the two drugs
are refampin and INH.
And that's sort of the consolidation phase
We can use less drugs because we've killed
the bulk of the tuberculous organisms, hopefully,
in that first two months and now we're giving
At the end of this therapy, which is
a typical six month period, if all goes well,
we do a chest x-ray at the end of therapy.
We determine that the chest x-ray is improved
from the first one that led us to the diagnosis
and that is the end of therapy.
Voiceover: However, there are some patients
that actually, we end up needed to treat longer
because they don't have the simple pulmonary form
of the disease or they have some underlying problem.
Voiceover: So, as if six months wasn't long enough,
you can actually have a longer treatment regimen?
And sometimes the things which are,
or the disorders that are often associated
with a longer duration of therapy
is if you have more severe disease.
So, for example, TB meningitis, you would
typically treat longer.
TB infection of the bones and joint
you would typically treat longer.
So-called miliary TB, you would treat longer
and even pulmonary TB where there's a big cavity
in the lung, often will be treated longer.
Another circumstance that yields, makes you
treat longer is if the patient is
co-infected with HIV or if the patient is pregnant.
Pregnancy creates a certain degree of immuno-suppression
and pregnant women are treated for longer duration's.
Finally, patients whose cultures remain positive
throughout treatment, or at least,
for more than two months into treatment,
if they remain positive, they get treated
for a longer period of time
and patients who have a resistant organism,
which we'll talk about at another video,
get treated for a longer period of time.
So, back to the patient that we're treating
just for the regular period of time,
for that six month interval.
There are a couple of very important treatment
protocols that you need to be aware of
as these patients are being managed.
The first is, one has to make sure
that they're taking their drug,
so that they're compliant with their medication.
Voiceover: That seems like it would be
pretty hard for a patient to take all these,
four medicines and then two medicines
everyday for six months.
And so, recognizing that this is a
challenge for patients to take multiple medications
for multiple months, you need to be aware
of that challenge and try to make the
taking of the medication as easy as possible.
And make sure that you are observing
that they are taking their medication.
And let's talk about that observing first.
This has been a huge benefit in the management
of patients with TB.
Recognizing the need, the desirability
and the benefit for something called
directly observed therapy, or DOT.
Directly observed therapy means exactly
what it sounds like.
A healthcare provider is making sure the patient
is taking their medication.
The reason that that's so important,
is that it will yield a higher cure rate,
if they are taking their medication consistently
and less likely that they will develop
a resistant organism.
So, DOT, directly observed therapy, is very important.
The other element of assuring compliance
is to make it as easy as possible
for the patient to take their medication.
Well, one strategy is, you can have them
take their medication three days a week
as opposed to every day and it appears
that the treatment is equally effective,
so under directly observed therapy,
you can have them take it just three times per week.
The patients need to be encouraged constantly
to take their medication, underscoring
why it's important that they do so.
There are some logistic issues that may help
For example, if you have convenient office hours
where the patient can come and see you
after their work.
Providing incentives and enablers to patients
for taking their medication.
For example, providing them meals
or giving them travel vouchers to come
into the clinic or to wherever you're seeing them.
And then there are some strategies
for simplifying the regimes. I've already
mentioned the one, which is three times
a week therapy.
There are also some combination medications
available in some countries that may be valuable
in enhancing compliance.
So, while we're busy assuring compliance
when we're seeing these patients on a
regular basis, we're also monitoring
to make sure that the outcome of their infection
is going well.
And so what that means is that we're
evaluating them clinically at regular intervals,
often every month or so, examining them.
We're also obtaining cultures from their,
if it's pulmonary TB, from their sputum,
at monthly intervals to make sure
that they become culture negative
in the anticipated two or less months.
If cultures aren't available, you can do
smears of their culture, but it's better
to get cultures when they're available.
So, that's all part of monitoring.
Another important part of monitoring patients
who are being treated for tuberculosis
is watching for side effects and we'll do those
for the RIPE again, for the four key antimicrobial's
used for treating common TB infections.
So, R again, is for refampin.
And the main side effects to keep in mind
about refampin are that it can cause hepatitis.
And so, if a patient develops clinical symptoms
and you think maybe hepatitis,
they get jaundice, for example.
You have to be recognized that refampin
is one possibility.
Another side effect of refampin
is decreased platelet counts.
That is thrombocytopenia and you need
to be aware of that.
And then a very important side effect of refampin
is drug-to-drug interactions.
Because refampin is a potent inducer
of certain enzymes in the liver,
cytochrome P450 enzymes, there can be
interactions with other drugs.
As it is side, refampin also may color
secretions red, like red urine and red tears
that may interfere with contact lenses,
but that's more of an annoyance
than a significant side effect.
With regards to INH, or isoniazid,
the main side effects to be familiar with again,
INH can cause hepatitis, especially in those
that already have a reason for having hepatitis,
for example, alcoholics.
And isoniazid can also cause a peripheral neuropathy.
Oftentimes, resulting from vitamin B6
or pyridoxine deficiency.
So you can take care of that
by prescribing pyridoxine at the same time.
That's especially true if the patient has poor nutrition,
an alcoholic, for example.
You can also get neuropathy in patients
with chronic renal, who are taking INH,
with chronic renal failure and diabetes
and so forth, but neuropathy is important
to keep in mind.
With regards to pyrazinamide, these individuals
may get high uric acid levels and resulting arthralgias.
They can even get overt gout and that
would be a reason for stopping the pyrazinamide.
And then finally, with regards to Ethambutol,
patients may develop an optic neuritis
which can impair their vision and that would be
a reason to stop Ethambutol therapy.
So, being familiar with these side effects
as you monitor the response of the patient
to therapy and as you monitor their compliance
is also an important part of the treatment
of active TB.