Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Drugs Tuberculosis (TB) Caused by Mycobacterium tuberculosis Antitubercular drugs treat all forms of Mycobacterium (MTB) TB is most commonly characterized by granulomas in the lungs: nodular accumulations of inflammatory cells (e.g., macrophages, lymphocytes) that are delimited (“walled off” with clear boundaries) and have a center that has a cheesy or caseated consistency Copyright © 2017, Elsevier Inc. All rights reserved.

Mycobacterium (MTB) Infections
Common infection sites Lung (primary site) Brain (cerebral cortex) Bone (growing end) Liver Kidney Genitourinary tract Copyright © 2017, Elsevier Inc. All rights reserved.

Mycobacterium (MTB) Infections (Cont.)
Aerobic bacillus Passed from infected: Humans Cows (bovine) and birds (avian) Much less common Copyright © 2017, Elsevier Inc. All rights reserved.

Tubercle bacilli are conveyed by droplets. Droplets are expelled by coughing or sneezing, and they then gain entry into the body by inhalation. Tubercle bacilli then spread to other body organs via blood and lymphatic systems. Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue. Copyright © 2017, Elsevier Inc. All rights reserved.

MTB: very slow-growing organism More difficult to treat than most other bacterial infections First infectious episode: primary TB infection Reinfection: chronic form of the disease Dormancy: may test positive for exposure but are not necessarily infectious because of this dormancy process Copyright © 2017, Elsevier Inc. All rights reserved.

Incidence 1950s TB in the United States TB incidence decreased in most years until about 1985 1985: TB incidence began to rise for the first time in 20 years because of the development of TB in patients coinfected with HIV. 1992: There was a resurgence peak in the United States, but it has decreased since that time. Copyright © 2017, Elsevier Inc. All rights reserved.

Incidence (Cont.) 2012: rate of 3.2 TB cases per 100,000 persons with a 5.4% and 6.1% decline in cases reported and case rate decline respectively 2012 reported TB cases: lowest recorded rate since national reporting began in 1953 Decline is attributed to intensified public health efforts aimed at preventing, diagnosing, and treating TB as well as HIV infection. Concern now: increasing number of multidrug-resistant tuberculosis (MDR-TB) cases Copyright © 2017, Elsevier Inc. All rights reserved.

Multidrug-Resistant Tuberculosis (MDR-TB)
TB infects one third of the world’s population. MDR-TB that is resistant to both isoniazid (INH) and rifampin Extensively drug-resistant tuberculosis (XDR-TB): relatively rare type of MDR-TB, resistant to almost all drugs used to treat TB, including the two best first-line drugs, INH and rifampin, as well as to the best second-line medications XDR-TB is of special concern for patients who have AIDS or are otherwise immunocompromised. Copyright © 2017, Elsevier Inc. All rights reserved.

Multidrug-Resistant Tuberculosis (MDR-TB) (Cont.)
Bedaquiline (Sirturo) 2013: Food and Drug Administration granted accelerated approval for bedaquiline (Sirturo) for the treatment of MDR-TB Inhibits mycobacterial adenosine triphosphate (ATP) synthase First drug in 40 years to treat TB with a new mechanism of action Side effects: headache, chest pain, nausea, QT prolongation Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Drugs (Cont.)
Second-line drugs: capreomycin cycloserine levofloxacin ethionamide ofloxacin kanamycin para-aminosalicyclic acid (PAS) Copyright © 2017, Elsevier Inc. All rights reserved.

Tuberculosis-Related Injections
Purified protein derivative (PPD) (Mantoux) A diagnostic injection given intradermally in doses of 5 tuberculin units (0.1 mL) to detect exposure to the TB organism Positive result is indicated by induration (not erythema) at the site of injection Copyright © 2017, Elsevier Inc. All rights reserved.

Tuberculosis-Related Injections (Cont.)
Bacille Calmette-Guérin (BCG) A vaccine injection derived from an inactivated strain of Mycobacterium bovis Used in much of the world to vaccinate young children against TB Does not prevent infection Reduces active TB by 60% to 80% Effective at preventing more severe cases involving dissemination of infection throughout the body Can cause false-positive results on the tuberculin skin test Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Drug Therapy Considerations
Major effects of drug therapy: reduction of cough and, therefore, reduction of the infectiousness of the patient Normally occurs within 2 weeks of the initiation of drug therapy if TB strain is drug sensitive Most cases of TB can be cured. Successful treatment: several antibiotic drugs for at least 6 months and sometimes for as long as 12 months Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Drug Therapy Considerations (Cont.)
Perform drug-susceptibility testing on the first Mycobacterium spp. that is isolated from a patient specimen to prevent the development of MDR-TB. Even before the results of susceptibility tests are known, begin a regimen with multiple antitubercular drugs (to reduce the chances of development of resistance). Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question
A patient with TB has been taking antitubercular drugs. A sputum culture is ordered to test for acid-fast bacilli. When is the best time for the nurse to obtain the sputum culture? In the morning Noon 5 pm 10 pm Correct answer: A Rationale: If the prescriber has ordered collection of a sputum specimen to test for acid-fast bacilli, it is best to obtain the sample early in the morning. The most common order is for three consecutive morning specimens, with a repeat specimen several weeks later. Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Drug Therapy Considerations (Cont.)
Adjust drug regimen after the results of susceptibility testing are known. Monitor patient compliance closely during therapy. Problems with successful therapy occur because of patient nonadherence to drug therapy and the increased incidence of drug-resistant organisms. Copyright © 2017, Elsevier Inc. All rights reserved.

Mechanism of Action Three groups: Protein wall synthesis inhibitors: streptomycin, kanamycin, capreomycin, rifampin, rifabutin, others Cell wall synthesis inhibitors: cycloserine, ethionamide, INH Other mechanisms of action: ethambutol, INH, PAS, ethionamide Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Therapy
Effectiveness depends on: Type of infection Adequate dosing Sufficient duration of treatment Adherence to drug regimen Selection of an effective drug combination Copyright © 2017, Elsevier Inc. All rights reserved.

Antitubercular Therapy (Cont.)
Problems: Drug-resistant organisms Drug toxicity Patient nonadherence MDR-TB Copyright © 2017, Elsevier Inc. All rights reserved.

Isoniazid Drug of choice for TB Resistant strains of Mycobacterium emerging Metabolized in the liver through acetylation—watch for “slow acetylators” Used alone or in combination with other drugs Contraindicated with liver disease Copyright © 2017, Elsevier Inc. All rights reserved.

A patient with a diagnosis of TB will be taking INH as part of the anti-TB therapy. When reviewing the patient’s chart, the nurse finds documentation that the patient is a “slow acetylator.” This means that: the dosage of INH may need to be lower to prevent INH accumulation. the dosage of INH may need to be higher because of the slow acetylation process. he should not take INH. he will need to take a combination of anti-TB drugs for successful therapy. Correct answer: A Rationale: When INH is taken by slow acetylators, the INH accumulates because there are not enough liver enzymes to break down the INH. Therefore, the dosages of INH may need to be adjusted downward to prevent toxicity. Copyright © 2017, Elsevier Inc. All rights reserved.

Adverse Effects INH: peripheral neuropathy, hepatotoxicity Ethambutol: retrobulbar neuritis, blindness Rifampin: hepatitis; discoloration of urine, stools, and other body fluids Copyright © 2017, Elsevier Inc. All rights reserved.

A patient is receiving INH for the treatment of TB. Which vitamin does the nurse anticipate administering with the INH to prevent INH-precipitated peripheral neuropathies? Vitamin C Vitamin B12 Vitamin D Vitamin B6 Correct answer: D Rationale: Pyridoxine (vitamin B6) may be indicated to prevent INH-precipitated peripheral neuropathies and numbness, tingling, or burning of the extremities. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications Obtain a thorough medical history and assessment. Perform liver function studies in patients who are to receive INH or rifampin (especially in older patients and those who use alcohol daily). Assess for contraindications to the various drugs, conditions for cautious use, and potential drug interactions. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.)
Patient education is critical. Therapy may last for up to 24 months. Take medications exactly as ordered at the same time every day. Emphasize the importance of strict adherence to regimen for improvement of condition or cure. Copyright © 2017, Elsevier Inc. All rights reserved.

Four weeks after beginning antitubercular drug therapy on an outpatient basis, the patient reports that he still experiences night sweats. What does the nurse identify as the main concern at this time? He is not taking his medication properly. More time is needed to see a therapeutic response. His infection may be resistant to the drug therapy ordered. He may have contracted a different strain of TB. Correct answer: C Rationale: The nurse should not jump to conclusions that the patient is not taking his medication properly. An improvement should start to occur within 2 weeks of starting drug therapy, but this may not occur if the patient’s TB is not sensitive to the prescribed drugs. An evaluation of the drug therapy will be needed. Copyright © 2017, Elsevier Inc. All rights reserved.

Patient education is critical. (Cont.) Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets. Teach patients to take care of themselves, including getting adequate nutrition and rest. Copyright © 2017, Elsevier Inc. All rights reserved.

Patients should not consume alcohol while taking these medications or take other medications, including over-the-counter medications, unless they check with their prescribers. Rifampin causes oral contraceptives to become ineffective; another form of birth control is needed. Copyright © 2017, Elsevier Inc. All rights reserved.

Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish orange; even contact lenses may be stained. Pyridoxine may be needed to combat neurologic adverse effects associated with INH therapy. Oral preparations may be given with meals to reduce gastrointestinal upset even though recommendations are to take them 1 hour before or 2 hours after meals. Copyright © 2017, Elsevier Inc. All rights reserved.

Monitor for adverse effects. Instruct patients on the adverse effects that should be reported to the prescriber immediately. These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, and jaundice. Copyright © 2017, Elsevier Inc. All rights reserved.

Monitor for therapeutic effects. Decrease in symptoms of TB, such as cough and fever Laboratory study results (culture and sensitivity tests) and chest radiographs should confirm clinical findings. Watch for lack of clinical response to therapy, indicating possible drug resistance. Copyright © 2017, Elsevier Inc. All rights reserved.

A patient has an extremely severe infection with a Mycobacterium that is resistant to all but one antitubercular drug; however, the patient has had an allergic reaction to that drug in the past. What does the nurse anticipate as being ordered for this patient? A combination of antitubercular drugs will be chosen to fight the infection. The patient will receive the drug and supportive care to help him tolerate the antitubercular therapy. The patient will remain on isolation precautions until his cough clears. There is nothing that can be done for this patient. Correct answer: B Rationale: It must be recognized that the urgency of treating a potentially fatal infection may have to be balanced against any prevailing contraindications. In extreme cases, patients are sometimes given a drug to which they have some degree of allergy with supportive care that enables them at least to tolerate the medication. Examples of such supportive care are treatment with antipyretics (e.g., acetaminophen), antihistamines (e.g., diphenhydramine), or even corticosteroids (e.g., prednisone, methylprednisolone). Copyright © 2017, Elsevier Inc. All rights reserved.

Case Study A home care nurse is visiting a patient with a diagnosis of TB. The patient traveled abroad 2 months ago. He lives with his wife and 5-year-old son. The patient tells the nurse that he is concerned his son will also get TB, so he wants to share his pills with his son. What is the best response by the nurse? “That is a good idea. Children should not be exposed to TB.” “You should give your son half of the dose you take.” “Do not share any of your medications with anyone. Contact your son’s health care provider to discuss your concerns.” “Children have an immune system that makes them immune to TB.” Correct answer: C Rationale: Medications of any kind should never be shared with any other person. In particular, antitubercular drugs are age specific. Assessment of age is also important because the likelihood of adverse reactions and toxicity is increased in older patients because of age-related liver and kidney dysfunction. Additionally, the safety of these drugs in children 13 years of age and younger has not been established. Copyright © 2017, Elsevier Inc. All rights reserved.

Case Study (Cont.) The patient tells the nurse, “I had a shot after I returned from my trip overseas. I thought that was supposed to stop me from getting a TB infection.” What information regarding TB-related injections does the nurse identify as being true? BCG is used to prevent infection with TB for women of childbearing age. A positive result for a PPD test is indicated by redness at the site of injection. PPD is a diagnostic injection given intradermally to detect exposure to the TB organism. BCG is a vaccine injection derived from an activated strain of Mycobacterium bovis. Correct answer: C Rationale: PPD is a diagnostic injection given intradermally in doses of 5 tuberculin units (0.1 mL) to detect exposure to the TB organism. A positive result is indicated by induration (not erythema) at the site of injection and is known as the Mantoux reaction, named for the physician who described it. BCG is used in much of the world to vaccinate young children against TB. Although it does not prevent infection, evidence indicates that it reduces active TB by 60% to 80% and is even more effective at preventing more severe cases involving dissemination of infection throughout the body. Copyright © 2017, Elsevier Inc. All rights reserved.

Case Study (Cont.) The patient’s wife is taking rifampin to prevent her from developing a TB infection. Which statement by the wife indicates that further teaching is needed? “Because my oral contraceptives will not work while I am taking rifampin, I will use another form of birth control.” “I will take the medication for 1 week and then stop.” “I will avoid prolonged exposure to the sun.” “My urine may turn a reddish color when taking rifampin.” Correct answer: B Rationale: Antitubercular therapy is taken for long periods of time, often 24 months. Although this patient does not have an active infection at this time and is taking the rifampin to prevent an infection, the nurse should further investigate the length of time the medication is ordered. All other statements are true. Copyright © 2017, Elsevier Inc. All rights reserved.

Copyright © 2017, Elsevier Inc. All rights reserved.

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