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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.