With the proper treatment, tuberculosis (TB, for short) is almost always curable. Doctors prescribe antibiotics to kill the bacteria that cause it. You’ll need to take them for 6 to 9 months. What medications you take and how long you’ll have to take them depends on which works to eradicate your TB. Sometimes, antibiotics used to treat the disease don’t work. Doctors call this "drug-resistant" TB. If you have this form of the disease, you may need to take stronger medications for longer. There are two types of TB -- latent and active. Depending on your risk factors, latent TB can re-activate and cause an active infection. That’s why your doctor might prescribe medication to kill the inactive bacteria -- just in case. These are the three treatment options:
If you have this form of the disease, you’ll need to take a number of antibiotics for 6 to 9 months. These four medications are most commonly used to treat it:
Your doctor may order a test that shows which antibiotics will kill the TB strain. Based on the results, you’ll take three or four medications for 2 months. Afterward, you’ll take two medications for 4 to 7 months. You’ll probably start to feel better after a few weeks of treatment. But only a doctor can tell you if you’re still contagious. If you’re not, you may be able to go back to your daily routine. If you have a TB strain that doesn’t respond to the usual medications used to treat TB, you have a drug-resistant strain. This means that you will be treated with a combination of second-line drugs, which may be less effective. You will need to take these drugs for a longer period of time. If several types of medications don't do the job, you have what doctors call “multidrug-resistant TB.” You’ll need to take a combination of medications for 20 to 30 months. They include:
A rare and serious type of the disease is called "extensively drug-resistant TB." This means that many of the common medications -- including isoniazid, rifampin, fluoroquinolones, and at least one of the antibiotics that are injected -- don't knock it out. Research shows that it can be cured around 30% to 50% of the time. Tell your doctor right away if you have any of the following symptoms: It’s important to take every dose of your antibiotics. Don’t stop, even if you feel better. If you don’t kill all of the bacteria in your body, the remaining germs can adapt and become drug-resistant. To help you remember, your doctor may need to watch you take your medication. This is called directly observed therapy. It’s recommended for treatment programs where you take antibiotics a few times a week instead of every day. If you have active TB of the lungs, you can infect other people. For that reason, your doctor will tell you to stay home during the first few weeks of treatment, until you’re no longer contagious. During that time, you should avoid public places and people with weakened immune systems, like young children, the elderly, and people with HIV. You’ll have to wear a special mask if you have visitors or need to go to the doctor’s office. Or your health care provider may admit you to the hospital until TB germs are no longer expelled in your cough. You may be hospitalized for a longer period if you cannot reliably take your medications, do not have stable housing, or have a multidrug resistant strain of TB. The goal is to prevent the spread of the disease. ABSTRACT: Tuberculosis (TB) is a deadly disease that affects one-third of the world’s population. Although the number of cases in the United States has declined over the past 20 years, more than 9,500 new cases of active TB were reported last year. Treatment for TB includes combination therapy with multiple medications taken over extended periods of time. These medications are often poorly tolerated, and drug interactions are common. A new drug, bedaquiline, was recently FDA-approved for treatment of multidrug-resistant TB (MDR-TB), and several new drugs are in development. It is important for pharmacists to be familiar with recommended treatment regimens for latent, active, and MDR-TB, as pharmacists play a large role in making drug therapy recommendations, identifying drug-drug interactions, and managing adverse events. In 2013, 9,588 new cases of active TB were reported in the United States, representing an incidence of 3.0 cases per 100,000 people.3 Although the number of cases in the U.S. has been declining over the past 20 years, we have missed the CDC goal of eliminating TB in the U.S., originally set for 2010.3,4 Over 11 million additional people in the U.S. have latent TB infection (LTBI), with approximately 300,000 patients treated each year.5 ,6 Despite a relatively low incidence of TB in the U.S., certain segments of people continue to be dispropor-tionally affected, including foreign-born residents, patients with HIV, and homeless people.3 In 2013, California, Texas, New York, and Florida accounted for 51.3% of all TB cases in the U.S.3 Pharmacists working in these states and with these patients are key stakeholders in providing effective medication management, identifying infected patients, and practicing infection control. While TB is an issue in the U.S., it is much more widespread in other regions of the globe. In 2012, one-third of the world’s population was infected and approximately 9 million new cases of TB occurred worldwide.7 The incidence in some countries is reported at >300 cases per 100,000 people, with countries in Africa and Asia being most affected.1 TB has a high mortality; it is estimated that 1.3 million TB-related deaths occur globally each year.7 Patients with TB can be asymptomatic initially or present with fever and pleuritic chest pain.1 Chronic cough, sputum production (sometimes bloody), weight loss, decreased appetite, fever, and night sweats may also develop over time in patients with pulmonary TB.1 ,8 There are two types of TB infection: active disease and latent infection. The risk of developing active TB after becoming infected depends largely on the status of the patient’s immune function. Patients with HIV and young children have increased risk of developing active disease.1 Patients with LTBI are not infectious; however, reactivation of disease can occur. It is estimated that up to 10% of infected people will develop active TB throughout the course of their lifetime, with increased risk during the first year post infection.1 The initial suspicion of active pulmonary TB is often based on an abnormal chest X-ray in the presence of respiratory symptoms.1 Upper-lobe disease with infiltrates and cavities is classically seen.1 For patients with suspected TB, a positive acid-fast bacilli–stained sputum smear provides strong evidence for diagnosis, but only the isolation of M tuberculosis organisms from a clinical specimen can provide definitive diagnosis.9 Once an organism is isolated, susceptibility testing must be done to guide therapy, which can take 3 to 8 weeks depending on the laboratory methods used.1 ,10 Skin testing with tuberculin-PPD, also known as a tuberculin skin test (TST), is the most widely used screening mechanism for LTBI.1 ,9 Blood tests that measure T-cell interferon-gamma release in response to stimulation with highly TB-specific antigens are also available and preferred for most people, as they are more specific.1 TB is most commonly transmitted through the airborne spread of droplet nuclei produced by infected patients.1 Prompt diagnosis and isolation of infectious patients are the best tools in the prevention of TB.1 ,11 The CDC recommends that all healthcare settings have a TB infection–control plan that is part of an overall infection-control program.11 Plans consist of three key components: administrative controls, environmental controls, and a respiratory-protection program.10 ,11 All healthcare employees practicing in hospitals and other patient-care settings should receive baseline TB screening and rescreening as warranted.11 Administrative and environmental controls minimize the number of areas in which exposure to M tuberculosis might occur. When respiratory protection is warranted, the minimum respiratory protection device is a filtering facepiece respirator (e.g., N95 disposable respirator), which healthcare workers and visitors should use when entering rooms with suspected or infectious patients.11 This is particularly important for pharmacists taking medication histories, participating in multidisciplinary rounds, or counseling patients before discharge. Pharmacologic treatment is the foundation of TB management. Drugs are given over weeks or months and often involve complex regimens. Active disease and latent infection are treated differently, and the specific path chosen varies depending on patient factors, including HIV status, extent of illness, presence of drug resistance, and tolerance of adverse events.1 Goals for the treatment of active TB include curing the patient and minimizing the infection of others.9 The management of active TB requires a minimum of two drugs, and often three or four, used in combination for >6 months.10 Directly observed therapy (DOT) by a healthcare professional is a standard of care, as compliance with treatment is essential to eradicating infection.10 TABLE 1 lists anti-TB drugs used in the U.S.9 ,10 Four different treatment regimens are recommended by the joint CDC, American Thoracic Society (ATS), and Infectious Diseases Society of America (IDSA) guidelines.9 ,10 Each regimen includes a combination of drugs given in two phases: initial and continuation. The initial, or bactericidal, phase eliminates the majority of M tuberculosis bacteria while also resolving symptoms and infectiousness.1 The continuation, or sterilization, phase kills persisting mycobacteria.1 Most regimens use isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) for 2 months, followed by INH and RIF for another 4 months.1 ,9 Empirical therapy with more than four drugs may be warranted when drug susceptibility patterns for the region or population are known.10 TABLE 2 outlines specific regimens.1 ,9,10 A full course of treatment is determined by the total number of doses taken, not duration of therapy.9 A sputum specimen and culture should be obtained and monitored monthly during the treatment of pulmonary TB, until two consecutive specimens are converted to negative on culture.9 The treatment of LTBI aims at preventing the occurrence of active disease.1 There are a variety of treatment regimens for LTBI, as listed in TABLE 3.5,10,12,13 A 9-month daily INH regimen has been the standard in the U.S.; however, self-administered regimens have completion rates of 60%, often as a result of the long duration of therapy.5 ,12,13 The combination of INH and rifapentine (RPT) administered once weekly for 12 weeks, as DOT, has been shown to be as effective as 9 months of INH and more likely to be completed.13 The CDC now recommends the 12-week RPT regimen as an equal alternative to the 9-month INH regimen for most patients aged >12 years who have LTBI and factors predictive of developing TB, including recent exposure to active TB and abnormal chest X-ray showing healed pulmonary TB, and for HIV co-infected patients who are otherwise healthy and not taking antiretrovirals.13 Multidrug-resistant TB (MDR-TB) describes disease that is resistant to at least INH and RIF; additional susceptibility testing for second-line agents should occur if MDR-TB is found.1 ,14 Two or more drugs susceptible to the patient’s isolate (which the patient has not had previously) should be added to the initial regimen to reduce the development of drug resistance.10 Extensively drug-resistant TB (XDR-TB) refers to MDR-TB with additional resistance to any fluoroquinolone and at least one of the injectable anti-TB drugs.14 XDR-TB poses significant treatment challenges, often requiring up to 2 years of treatment.14 A TB specialist should be consulted to help manage these difficult-to-treat patients. Currently, there is no standard treatment for MDR-TB, with typical treatment including the use of five or six drugs in combination over extended periods of time.1 ,14 Bedaquiline (Sirturo) was approved by the FDA in December 2012 for use up to 24 weeks in combination therapy for pulmonary MDR-TB in adults.14 ,15 The CDC followed shortly with provisional treatment guidelines in 2013.14,15 Bedaquiline has a unique mechanism of action, represents a novel class (diarylquinoline), and was the first medication FDA-approved in over 40 years for the treatment of TB.16 Bedaquiline inhibits mycobacterial ATP synthase, an enzyme essential for the generation of energy in M tuberculosis.15,16 Bedaquiline was approved based on two placebo-controlled trials, where bedaquiline plus culture-directed background therapy showed decreased time to culture conversion and improved culture conversion rates compared to placebo plus other drugs.15 The most common adverse reactions reported in patients were nausea, arthralgia, and headache. Boxed warnings about increased mortality and QT prolongation are also included in the prescribing information.15 Drug-induced hepatitis is the most common serious adverse effect of anti-TB medications.9 INH, RIF, and PZA can all cause hepatic injury and should be discontinued and replaced if hepatitis occurs.9 Once liver enzymes stabilize and symptoms improve, a rechallenge with the first-line medications should be attempted.9 Gastrointestinal (GI) upset is a common occurrence in the first few weeks of treatment.9 Taking medication with food may help reduce or alleviate some of the GI effects; therapy should not be discontinued unless absolutely necessary.9 While there are many adverse events possible with these agents, other significant events for pharmacists to be aware of include peripheral neuropathy with INH, urine discoloration with RIF and rifabutin, elevations in the serum uric acid concentrations with PZA, and vision disturbances with EMB.9,10 Medication compliance is key to successful TB treatment.9 Pharmacists should stress the importance of compliance when counseling patients prior to hospital discharge. If a patient is noncompliant, reinitiating treatment should take into account the point in time when the noncompliance occurred, the duration of time the patient has been without medication, and the patient’s bacillary load.9 Anti-TB medications should be administered together at the same time, as this reduces the risk of acquired drug resistance. Fixed-dose combination products, such as Rifamate (INH/RIF) and Rifater (INH/RIF/PZA), may be beneficial, as they are administered more easily than single drug tablets and reduce patient dosing errors.10 The drugs used to treat TB affect the metabolism of many other drugs, including antiretrovirals and anti-infectives.10 Most of the clinically relevant drug-drug interactions involving anti-TB drugs are due to CYP450 induction by the rifamycins (RIF, rifabutin, and RPT); RIF is the most potent inducer of the three.10 Some HIV patients may benefit from the use of rifabutin instead of RIF or alternate antiretroviral regimens, as RIF’s induction of CYP3A4 may greatly decrease serum levels of protease inhibitors and selected nonnucleoside reverse transcriptase inhibitors.9,10 Pharmacists play an important role in identifying and managing drug-drug interactions in TB patients with and without HIV co-infection. In recent years, a renewed focus on anti-TB medications has generated promising research into new agents.16 Several new classes of anti-TB medications are currently under development; some with novel mechanisms of action.2 ,17 These drugs offer the possibility of shortened regimens and more effective treatment for MDR-TB.2,17 TABLE 4 provides a brief overview of some investigational therapies.16,17 In places where TB is endemic, the bacille Calmette- Guérin (BCG) vaccine is routinely administered to infants at birth.2 Unfortunately, it has about 50% efficacy for the prevention of TB and produces a subclinical infection, which can result in a positive TST.2 The BCG vaccine is not routinely administered in the U.S.; however, it is being considered for adult travelers to areas with high prevalence of MDR-TB. There are >30 vaccines in development worldwide, with the hope of controlling TB spread in the future.2 Pharmacists play an important part in the management of TB. They can evaluate drug-drug interactions and recommend alternative agents when appropriate. They can also educate patients on expected adverse events and help manage events if they occur. Pharmacist counseling at initiation of treatment, including at hospital discharge, should focus on the importance of medication compliance. Pharmacists can help identify barriers to treatment compliance and those patients who could benefit from DOT. Pharmacists should remember to follow protection precautions to prevent the transmission of TB. 1. Raviglione MC, O’Brien RJ. Tuberculosis. In: Longo DL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill Professional; 2012.
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What pharmacologic therapies are available for the treatment of active pulmonary tuberculosis?
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