Microbiology 

Pathophysiology 

Clinical Presentation 

Diagnosis 

Therapy 

PHARMACOLOGIC THERAPY 
Chemoprophylaxis 

Active Disease 

HIV Disease 

Drug-Resistant TB 

Directly Observed Therapy 

Antituberculosis Drugs 

CONCLUSIONS

REFERENCES

CERTIFICATION

Pharmacotherapy of Tuberculosis

Catherine M. Oliphant, PharmD, and Scott M. Bonnema, PharmD

Dr. Oliphant is Assistant Professor of Pharmacy Practice at the University of Wyoming School of Pharmacy in Laramie, Wyoming. Dr. Bonnema is a Consultant Pharmacist at Emmissary Pharmacy and Infusion in Casper, Wyoming.

Introduction

Tuberculosis refers to infection with the bacterium Mycobacterium tuberculosis. Infection may be latent without significant symptoms, or may result in active disease (commonly referred to simply as tuberculosis or TB). Although once thought to be a disease that would eventually disappear, TB remains a global dilemma. TB is the leading infectious cause of death worldwide, predicted to cause 3.5 million deaths in 2000. Approximately one third of the world’s population is infected with M tuberculosis (MTb). Of these, 23% will die as a result of TB.^1-3 Crowded living conditions, declining socioeconomic conditions, and the HIV epidemic have all led to a recent resurgence in TB. Despite these grave statistics, TB is a very treatable disease. Response rates to effective therapy are excellent when patients are compliant with their medications. Given the importance of patient compliance and the nature of the medications used to treat TB, the pharmacist can play a key role in the care of patients with TB.

Epidemiology

After a time during which the incidence of TB steadily declined in the United States, attention was once again focused on this disease in the 1990s. Between 1953 and 1985, the number of TB cases decreased by 74% to a rate of 9.3 cases per 100,000. However, between 1985 and 1992, the number of TB cases rose by 20% to 10.5 cases per 100,000 in 1992.³ This rise was caused by a number of factors, including: the HIV epidemic, increased immigration from TB- endemic countries, deterioration of the infrastructure of TB services, declining social situations for some populations, and development of multidrug-resistant TB (MDR TB).^4,5 Improved TB-control efforts have once again led to a decrease in cases in the United States to a rate of 6.8 per 100,000 in 1998.⁵

TB is most prevalent in persons of low socioeconomic status. Populations at highest risk include the homeless, alcoholics, young urban minorities, drug abusers, prison inmates, and the poor. Of note, many of these populations are also associated with high rates of HIV seropositivity, an important risk factor for TB.^3-6 HIV-infected patients are very susceptible to infection with M tuberculosis and are also more likely to progress to active tubercular disease.³ In the United States in 1990, more than 5% of patients infected with HIV were co-infected with M tuberculosis and 39% of patients diagnosed with TB were also infected with HIV.⁷ In the United States approximately 4.2% of all HIV-positive patients have active TB, a rate that is 500 times that of the general population.³

Minorities have a much higher incidence of TB, with case rates per 100,000 of 4.2 for whites, 18.9 for Native Americans, 21.4 for Hispanics, 33.0 in African Americans, and 41.6 in Asian/Pacific Islanders.⁶ The elderly, especially those in nursing homes, are also at risk, with rates of infection as high as 39.2 per 100,000.³ Men have infection rates twice that of women. Health care workers in hospitals and long-term care facilities are also at increased risk. This is especially true for respiratory therapists and pulmonologists.⁷

Globally TB is a much larger problem. TB is the leading infectious cause of death worldwide. It is estimated that one third of the world’s population is infected with M tuberculosis.^4,6,7 In the year 2000, 3.5 million deaths are predicted worldwide from TB.³ Of these, 85% will occur in Africa, southeast Asia, and the western Pacific region. In Africa, 50% to 80% of adults are infected with TB, compared with a rate of only 0.4% in the developed world.³ These statistics underscore the importance of TB worldwide as well as in the United States. Eradication of TB in this country will not likely be accomplished without a significant decrease in worldwide infection rates.

Microbiology

M tuberculosis is an aerobic, slow-growing bacilli.^6,7 M tuberculosis does not stain well with Gram’s stain, therefore, other staining methods must be used for identification. Mycobacterium are often referred to as acid-fast bacilli (AFB).⁷ An acid-fast stain is often used to test for the presence of mycobacterium. Humans are the only known reservoir for M tuberculosis.⁶ Most species of mycobacterium grow very slowly with typical generation times approaching 24 hours compared to between 20 and 40 minutes for most bacterium.^6,7 Drug resistance is a growing problem in the treatment of tuberculosis. In 1998, 8.1% of U.S. isolates were resistant to isoniazid, while 1.1% were resistant to isoniazid and rifampin. Strains resistant to both isoniazid and rifampin 
are termed multidrug-resistant tuberculosis and are very difficult to treat.⁸

Pathophysiology

TB is transmitted by airborne droplets during the act of coughing, sneezing, or speaking.^6,9 Coughing and speaking for 5 minutes can produce about 3,000 infectious droplets, whereas sneezing generates an even greater number.⁶ Droplets containing M tuberculosis that are 1 to 4 microns may deposit in the middle lung where bacterial replication occurs. Risk of infection after exposure to M tuberculosis depends on many factors, including bacterial load, the environment in which exposure occurs, and infectiousness of the source. Transmission may occur in as many as 27% to 35% of close household contacts of patients with smear-positive active TB.^6,9 The immune status of the host is another important factor; immunosuppressed patients (particularly HIV-infected patients) are highly susceptible to infection with M tuberculosis.⁹ 

After infection of the lung tissue, macrophages carry the bacteria to the lymphatic or systemic circulation, possibly resulting in multiple sites of infection.^3,9 Approximately 3 to 9 weeks after infection, the development of cellular immunity results in a positive skin test.^3,6 In many immunocompetent individuals, the initial immune response destroys a large portion of the bacteria and halts further replication and dissemination.⁶ 

Approximately 5% to 15% of patients who are infected with M tuberculosis who do not receive appropriate drug prophylaxis at the time of conversion will develop active TB over the course of their lifetime. Most patients who progress to active TB will do so in the first 2 years of infection. In sharp contrast, HIV-positive patients have a 37% chance of developing active TB within the first 5 months of infection. Risk factors for progression to active TB are outlined in Table 1.^3,6 

Table 1. Risk Factors for Progressing 
from Infection to Active TB^3,6

Clinical Presentation

The majority of patients with active tubercular disease will present with pulmonary symptoms. Patients will often report vague symptoms, such as a persistent, productive cough, difficulty breathing, chest pain, and possibly hemoptysis (a sign of more advanced disease). Other nonspecific symptoms include weight loss, fever, night sweats, loss of appetite, and general malaise.^1,7,10 A typical chest X-ray in patients with TB includes findings of patchy or nodular infiltrates with cavitation often seen as disease progresses.⁷ As a part of the immune response to M tuberculosis, a cavitation results in which the bacteria are isolated from the body tissue, but not destroyed altogether. Organisms may be discharged from a cavity, free to infect other lung tissues.⁶

As the bacterial load increases in the untreated individual, patients may develop ulceration of tissues “bathed” in pulmonary secretions with a high concentration of bacteria. This may result in pharyngeal ulcers, nonhealing ulcers of the mouth and tongue, and/or laryngeal ulcers.⁶ As the disease progresses, patients may develop cyanosis and clubbing of digits as a result of poor oxygenation.⁷ Patients with advanced disease may have significant lung necrosis and cavitation.¹¹ The mortality rate for active, untreated TB is approximately 50%. With currently available treatments in the United States, few patients that are appropriately managed die from TB. However, as mentioned above, this is far from the case worldwide.³

The majority of patients with TB will exhibit pulmonary symptoms, however, approximately 15% to 20% of patients will develop manifestations of extrapulmonary disease, including meningitis, bacteremia, lymphadenitis, genitourinary tract infection, osteomyelitis, and miliary (disseminated) disease. The rate of extrapulmonary TB is much higher in patients with HIV/AIDS.^4,7

Diagnosis

The initial step in the diagnosis of TB is identifying those patients who are infected with M tuberculosis. The primary method of detecting infection is the tuberculin skin test with purified protein derivative (PPD). This test is performed by placing a 5 tuberculin unit PPD dose intracutaneously on the forearm. The test is then read by an experienced individual in 48 to 72 hours, and a record is made of the size of induration. It is important to measure only the induration (area of tissue elevation) and not the size of erythema (area of redness). A reaction of Ž5 mm is considered positive for HIV-infected patients, recent close contacts, young children, or a chest X-ray consistent with healed TB. A reaction of ~10 mm induration is considered positive for immunocompetent patients at risk for infection, such as patients born in countries with a high prevalence of TB, intravenous drug abusers, the poor, nursing home residents, health care workers, and patients with medical conditions increasing risk (including diabetes mellitus, end-stage renal disease, immunosuppressive drug therapy). For all other patients, an induration Ž15 mm is considered positive.^7,9-12 

Patients who have a positive skin test and patients who have symptoms consistent with active TB should undergo further diagnostic testing. Chest X-rays may be valuable in making the diagnosis of TB. Sputum (or other infected fluid) should be collected and tested for AFB, cultured, and tested for drug susceptibility. Because of the slow growth of mycobacterium, a sputum sample may take between 3 and 6 weeks to see visible colonies on culture.6 This makes selection of appropriate antitubercular therapy difficult as it may take a month or more to generate susceptibility data. However, new diagnostic tests have greatly reduced this time.

Therapy

Appropriate use of chemotherapeutic agents is required for a successful outcome. In patients who have active disease, a minimum of two drugs active against the organism are generally used. The duration of therapy is dependent on the host, underlying conditions, extent of disease, and susceptibility of the organisms. In patients with latent disease (infection), monotherapy may be appropriate, depending on the circumstances. 

Multiple-drug therapy is necessary for several reasons. The first reason being that three populations of mycobacteria are thought to be present in the body and certain chemotherapeutic agents work best against each type of population. Large, rapidly multiplying numbers of organisms (107 to 109) are present extracellularly often within cavities. Drug-resistant mutants are common in this population of mycobacteria. Agents that are most effective against these organisms include isoniazid, rifampin, and streptomycin. A second population is a slow or intermittently multiplying, small group (104 to 105) found in the closed lesions (caseous lesions). Resistant mutants are also found in this population.

Chemotherapeutic agents effective against this population include isoniazid and rifampin. The last population of M tuberculosis are the slowly multiplying organisms (104 to 105) present inside macrophages (an acidic environment). Drug-resistant mutants are also present in macrophages. Agents that are most effective against this population include pyrazinamide, rifampin, isoniazid, and quinolones. Therefore, multiple drugs are required to eradicate each of the subpopulations of M tuberculosis that exist within the host. Second, multidrug therapy is necessary to prevent the emergence of resistant strains of M tuberculosis . Lastly, multiple-drug therapy is required to sterilize the sputum and lesions as quickly as possible, decreasing the chance of disease transmission. The duration of therapy for TB is prolonged (6 months minimum) because of the slow and intermittently growing subpopulations of M tuberculosis.^7,13 

Pharmacologic Therapy

Chemoprophylaxis 

Patients with latent disease (M tuberculosis infection) may receive treatment to reduce the risk of developing active disease. It is thought that the use of prophylaxis will play a critical role in the reduction and eventual eradication of TB. The rationale for chemoprophylaxis is that the first 2 years after PPD conversion are associated with the highest risk for developing active disease. Isoniazid prophylaxis is associated with a 60% to 98% reduction in the development of active disease.¹³ Prophylaxis should be recommended in the following groups if the PPD is positive^6,13,14 

Isoniazid has traditionally been used for chemoprophylaxis. It is still considered the primary therapy for TB infection. Isoniazid in doses of 5 to 10 mg/kg per day not to exceed 300 mg/day (normal adult dose is 300 mg/day) is given for 6 to 12 months. The 12-month regimens are more effective than the 6-month regimens however the 6-month regimen is the standard recommendation in most cases. Isoniazid causes pyridoxine deficiency by one of two mechanisms. The first is that it may enhance pyridoxine elimination and secondly it may compete with pyridoxine, which is a cofactor involved in the synthesis of synaptic neurotransmitters.^6,7,15,16 Pyridoxine (vitamin B6) 10 to 50 mg/day may also be administered concomitantly with isoniazid to reduce the incidence of peripheral neuropathy (high-risk patients—malnourished, diabetics, alcoholics). Patients who cannot tolerate isoniazid, or in cases in which the index case (source) is resistant to isoniazid, can receive rifampin alone or in combination with pyrazinamide or ethambutol. The rationale for combination therapy is that rifampin monotherapy may be associated with the emergence of rifampin resistance. Regimens include rifampin 600 mg QD x 6 months or rifampin plus ethambutol or pyrazinamide.^6,7 In cases of resistance to both isoniazid and rifampin (multidrug resistance), chemoprophylaxis regimens should be based on the known or presumed susceptibility pattern of the index case. Several options include pyrazinamide plus ethambutol for 6 to 12 months, pyrazinamide or ethambutol plus a quinolone (eg, ciprofloxacin or ofloxacin) for 6 to 12 months.^6,7

Isoniazid toxicity has been a recurring debate for years. Isoniazid is associated with the risk of hepatitis that appears to be more prevalent in individuals more than 35 years of age. The risk of hepatitis increases with age (<20 years—negligible; 20 to 24 years—0.3%, age 35 to 39—1.2%; >50 years—2.3% to 3%), however careful monitoring of liver enzymes in individuals more than 35 years of age may reduce the potential for hepatitis.¹³ The American Thoracic Society recommends that the following PPD-positive groups be considered for isoniazid prophylaxis, regardless of age: HIV-positive, close contacts of TB cases, persons with fibrotic lesions on chest X-ray, and children.¹⁷ It is also recommended that the following groups be considered for isoniazid prophylaxis if younger than 35 years of age: foreign-born individuals from areas of high prevalence, medically underserved populations, residents of long-term care facilities, health care workers, or those with no risk factors.¹⁷ Other experts suggest consideration of isoniazid administration to individuals more than 35 years of age as data indicate that the benefit outweighs the risk of hepatitis.^7,13,18 

Active Disease 

As previously mentioned, effective therapy requires a minimum of two agents that are active against M tuberculosis. Initial therapy should be guided by the index case’s drug susceptibility results, however this is often not known. In 1993, the Centers for Disease Control and Prevention (CDC) modified its initial drug regimen recommendation in response to the increase in TB and the emergence of drug-resistant TB. The CDC now recommends that initial, empiric therapy be with a four-drug regimen. Initial therapy with only two agents is discouraged because two active agents must be used for effective therapy, and in this era of resistance, one would not know which two agents might be susceptible. Currently, the initial, empiric four-drug regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin. This ensures that at least 95% of patients will receive a regimen in which their M tuberculosis will be susceptible to at least two agents. In areas where isoniazid resistance is known to be less than 4%, an initial, empiric regimen may consist of three drugs—isoniazid, rifampin, and pyrazinamide.^7,13,19,20 

Several options exist for initial therapy. One option is to administer isoniazid, rifampin, and pyrazinamide daily for 8 weeks followed by 16 weeks of daily or 2 to 3 times/week isoniazid and rifampin. In addition, ethambutol or streptomycin should be added initially until susceptibility to isoniazid and rifampin are known. Total duration of therapy is a minimum of 6 months, or 3 months beyond culture conversion to negative, whichever is greater. When intermittent therapy (eg, 2 to 3 times/week) is used, directly observed therapy (DOT) is recommended. DOT is a method of ensuring adherence to the treatment regimen and will be discussed further. Another option is to administer isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin daily for 2 weeks followed by 2-times/week administration of the same agents for 6 weeks followed by isoniazid and rifampin 2 times/week for 16 weeks. Again, DOT is highly recommended and essential when intermittent therapy is administered. The third option is to administer isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin 3 times/week for 6 months by DOT. If streptomycin is used, it may possibly be discontinued after 4 months if the M tuberculosis is susceptible to all agents.^7,13,19,20

Prior to administration of chemotherapeutic agents, a sputum specimen should be obtained for acid-fast stain and culture. Once the initial specimen is obtained therapy may begin. Sputum specimens should be obtained every few days until smears are negative for AFB. The patient can be removed from isolation once the smear is negative. Cultures should be done every 2 weeks until negative and then monthly thereafter. It normally takes 2 to 3 months for culture conversion to negative. If cultures remain positive after 3 months, repeat susceptibility testing should be performed as resistance may have emerged.^6,19,20

HIV Disease 

Individuals with HIV are at an increased risk for primary or reactivation TB. Worldwide, it is estimated that approximately one third or more of individuals infected with HIV are also infected with M tuberculosis. In the United States, approximately 8% of HIV-infected individuals are also infected with M tuberculosis. HIV coinfection must be considered in an individual with TB. TB has detrimental effects on the course of HIV infection. TB is known to increase HIV replication as well as the progression of HIV disease. Mortality in HIV-infected individuals with TB is at least four times higher than both non-HIV-infected individuals and HIV-infected persons without TB. It has also been noted that MDR TB is more prevalent among patients who are HIV-infected. Risk factors for poor survival in HIV-infected patients include a low CD4 count, MDR TB, history of intravenous drug abuse, no DOT, and extrapulmonary TB.^{6,13,14,21-23} Anergy testing is no longer recommended in patients with HIV infection. It has also been noted that TB prophylaxis may not be necessary in HIV-infected, anergic individuals unless the person has had close contact with an active TB case.^22,24-26 

The rate of TB disease in HIV- infected, PPD-positive patients is 4 to 26 times that of PPD-negative, HIV-infected individuals. The rate is 200 to 800 times that of the non-HIV-infected population. Therefore, prophylaxis of latent TB is of utmost importance. The currently recommended regimen for prophylaxis in HIV-infected persons is isoniazid 300 mg daily for 12 months. However, studies have shown that the optimal duration of therapy must be greater than 6 months but not longer than 12 months (increased isoniazid toxicity with therapy > 12 months). Data have shown that a 9-month regimen may be sufficient. It has also been noted that isoniazid may be administered daily or twice a week. Several short- course regimens have been evaluated and have shown to be as effective as the longer regimens. Rifampin 600 mg daily plus pyrazinamide 20 mg/kg daily for 2 months has shown comparable protection as isoniazid for 12 months.²⁷ However, since rifampin is a potent cytochrome P-450 (CYP450) inducer, rifabutin (a less potent CYP450 inducer than rifampin) is recommended in place of rifampin in most instances if the patient is on a protease inhibitor, nonnucleoside reverse transcriptase inhibitor (NNRTI), or methadone. Rifabutin must be dose-adjusted and is not recommended to be used in combination with ritonavir, saquinavir, or delavirdine because of their effects on rifabutin metabolism. If an interaction cannot be avoided, use of the longer isoniazid regimen is recommended.^{14,22,23,26,28,29} Caution must always be exercised when adding an interacting agent to an antiretroviral regimen.³⁰ 

Patients with active TB and HIV are often treated with regimens similar to non-HIV-infected patients. In general, a 6-month regimen is considered appropriate if the clinical and bacteriologic responses are not prolonged. The management of HIV-infected patients becomes more challenging if the patient is also receiving antiretroviral therapy with a protease inhibitor or NNRTI. For patients who are not currently receiving antiretroviral therapy or a regimen containing a protease inhibitor or NNRTI, the preferred regimens are the same as for non-HIV-infected patients (eg, initially, a four-drug regimen). A 6-month regimen is recommended, however some physicians may prefer to treat for a total of 9 months. The regimen must be continued for an extended period of time if clinical or bacteriologic responses are prolonged.^19,22,23 For patients receiving antiretroviral therapy with a protease inhibitor or NNRTI, a 6-month regimen consisting of isoniazid, rifabutin, pyrazinamide, and ethambutol administered either daily for 8 weeks or daily for 2 weeks followed by twice a week for 6 weeks. This regimen is then followed by daily or twice-a-week administration of isoniazid and rifabutin (depending on susceptibilities) for 4 months. If a rifamycin (rifampin or rifabutin) cannot be used, a 9-month regimen consisting of isoniazid, streptomycin, pyrazinamide, and ethambutol daily for 8 weeks or daily for 2 weeks followed by twice-a-week dosing for 6 weeks must be initiated. This is then followed by 7 months of 2-to-3-times-a week administration of isoniazid, streptomycin, and pyrazinamide.^22,23 Antiretroviral therapy should not be altered to facilitate selection of a simpler TB regimen. Therefore, if a patient is on a protease inhibitor this must be taken into account when choosing the most appropriate regimen for this individual. If a patient is started on an antiretroviral regimen while receiving anti-TB therapy, this must be considered and the TB regimen may need to be adjusted (eg, discontinue rifampin and start rifabutin or change to a non-rifamycin-containing regimen).³⁰ 

Drug-Resistant TB 

Drug resistance in TB occurs as a result of chromosomal mutations leading to resistance to individual antimycobacterial agents. All populations of M tuberculosis have naturally occurring drug-resistant organisms. The frequency of isoniazid resistance is estimated at 3 x 10-8 and for rifampin it is estimated to be 2 x 10-10 mutations per organism. The frequency of both isoniazid and rifampin resistance is 6 x 10-18. Resistance to both isoniazid and rifampin is known as multidrug resistance. The probability of this occurring naturally is low.19,20,31 However, both primary and acquired drug resistance occur. Primary resistance occurs in a patient who has never been treated for TB. Primary resistance risk factors include exposure to an index case with drug-resistant TB, living in or being exposed to a geographic area with a high rate of drug-resistant TB, minority groups, children, intravenous drug use, and HIV infection. Acquired drug resistance occurs when the patient is initially infected with a susceptible strain of M tuberculosis but during therapy drug-resistant M tuberculosis emerges. This emergence of drug-resistant M tuberculosis occurs as a result of patient nonadherence, single-drug therapy or therapy that approximates single-drug therapy, coexisting HIV infection, and drug malabsorption.²⁰ 

Therapy for drug-resistant TB should be based on susceptibility results. However, initial, empiric therapy for suspected, drug-resistant M tuberculosis TB should include five or six drugs. This regimen should include isoniazid, rifampin, pyrazinamide, ethambutol or streptomycin, and one or two second-line agents. Once susceptibility data are available, the regimen may be streamlined depending on the results. Resistance to isoniazid and/or rifampin usually results in a longer duration of therapy because these two agents are the most effective anti-TB agents. For example, rifampin monoresistance results in a duration of therapy of 18 months. Isoniazid monoresistance can be treated anywhere from 6 to 12 months depending on the regimen. Resistance to both isoniazid and rifampin leads to a prolonged course of therapy (18 months after sputum conversion) with a minimum of three to four agents. As the number of drugs the M tuberculosis is resistant to increases, so does therapy with multiple agents (often five or more) as well as duration of therapy (up to 24 months after culture conversion).^20,31

Directly Observed Therapy 

The resurgence of TB and the emergence of MDR TB has forced us to consider methods of controlling TB. Since we know that acquired drug resistance is in part a result of patient nonadherence, DOT is a strategy to ensure adherence. Adherence is referred to as patients taking medication as prescribed. Nonadherence can lead to therapy failure, drug resistance, relapse, prolonged infectiousness, and increased transmission to others who are in contact with the index case of TB. Nonadherence that leads to failure of therapy leads to increased patient care costs (eg, medications, hospitalizations) as well as a potential increase in the number of new TB cases. TB therapy involves the use of multiple medications and a long duration of administration (minimum of 6 months). Many patients are symptom-free after several months of therapy, further increasing nonadherence.^32-36 

DOT involves another individual, usually a health care worker, observing the patient taking their TB medications. DOT has been shown to increase treatment completion rates from 42% to 82% (nonsupervised therapy) to 86% to 96.5%. The CDC, American Thoracic Society, and the World Health Organization generally recommend DOT for all active TB cases.³⁰ More often DOT is recommended for alcoholics, substance abuse patients, homeless persons, HIV-infected patients, drug-resistant TB, history of nonadherence or TB relapse, psychiatric disorders, slow sputum conversion, and those patients who are too ill to manage their own therapy. Others also recommend DOT for individuals receiving less than daily administration of therapy (eg, 2-to-3-times-per week therapy). DOT strategies include clinic visits, food/clothing/ transportation incentives, and “home” visits.^32,33,35,36 

Antituberculosis Drugs

Antituberculosis drugs are divided into primary (first-line) and secondary agents. A TB regimen should consist primarily of first-line agents. Primary agents include isoniazid, rifampin/rifabutin, pyrazinamide, ethambutol, and streptomycin. Isoniazid and rifampin are the mainstays of therapy. Regimens that do not include either of these agents must be continued for an extended period of duration. Secondary agents are less efficacious and may be more toxic than the primary drugs. Second-line agents include capreomycin, ethionamide, kanamycin, amikacin, para-aminosalicylic acid, cycloserine, and quinolones. See Table 2 for recommended doses, adverse effects, drug interactions, and patient counseling information. Other agents that may be used in the treatment of MDR TB include clofazamine, amoxicillin/clavulanate, and imipenem/cilastatin.²⁰ 

Table 2.  Antituberculosis Drugs^{7, 15, 16, 17,37}   

Conclusions

Despite great advances in the treatment of TB in the 20th century, it remains the number-one infectious killer worldwide. Rates of infection are once again on the decline in this country, yet one outbreak can affect a great number of individuals. While eradication of TB remains a goal in this country, it will not be accomplished without a global approach to the management of TB. The unique nature of the medications used to treat TB, the importance of patient compliance, the complexity of anti-tubercular drug regimens, and the number of adverse reactions and drug-drug interactions associated with these medications all allow the pharmacist to play a crucial role in the treatment of patients with TB.

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INTRODUCTION  |  REFERENCES

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