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  • 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

  • of therapy.

  • 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

  • consolidated therapy.

  • 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: Okay.

  • 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?

  • Voiceover: Exactly.

  • 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.

  • Voiceover: Exactly.

  • 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

  • assuring compliance.

  • 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,

  • are hepatitis.

  • 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.

Voiceover: This is Charles Proburg.

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