Chapter 41

Antitubercular Drugs

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. 2
 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. 3

 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. 4

 Mycobacterium (MTB)
Infections (Cont.)
 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. 5

 Mycobacterium (MTB)
Infections (Cont.)
 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. 6

 Diagnosis

Copyright © 2017, Elsevier Inc. All rights reserved. 7

 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. 8

 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. 9
 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. 10

 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. 11
 Antitubercular Drugs

 First-line drugs :
 INH: primary drug used
 rifapentine
 ethambutol
 rifabutin
 pyrazinamide (PZA)
 rifampin
 streptomycin

Copyright © 2017, Elsevier Inc. All rights reserved. 12

 Antitubercular Drugs (Cont.)

 Second-line drugs:
 capreomycin
 cycloserine
 levofloxacin
 ethionamide
 ofloxacin
 kanamycin
 para-aminosalicyclic acid (PAS)

Copyright © 2017, Elsevier Inc. All rights reserved. 13

 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. 14

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. 15
 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. 16

 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. 17

 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?

A. In the morning
B. Noon
C. 5 PM
D. 10 PM

Copyright © 2017, Elsevier Inc. All rights reserved. 18

 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. 19

 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. 20

 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. 21

 Antitubercular Therapy (Cont.)

 Problems:
 Drug-resistant organisms
 Drug toxicity
 Patient nonadherence
 MDR-TB

Copyright © 2017, Elsevier Inc. All rights reserved. 22

 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. 23

 Audience Response System Question

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:
A. the dosage of INH may need to be lower to prevent INH
accumulation.
B. the dosage of INH may need to be higher because of
the slow acetylation process.
C. he should not take INH.
D. he will need to take a combination of anti-TB drugs for
successful therapy.

Copyright © 2017, Elsevier Inc. All rights reserved. 24

 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. 25

 Audience Response System Question

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?

A. Vitamin C
B. Vitamin B12
C. Vitamin D
D. Vitamin B6

Copyright © 2017, Elsevier Inc. All rights reserved. 26

 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. 27

 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. 28

 Audience Response System Question

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?

A. He is not taking his medication properly.

B. More time is needed to see a therapeutic response.
C. His infection may be resistant to the drug therapy
ordered.
D. He may have contracted a different strain of TB.

Copyright © 2017, Elsevier Inc. All rights reserved. 29

 Nursing Implications (Cont.)

 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. 30

 Nursing Implications (Cont.)

 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. 31

 Nursing Implications (Cont.)

 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. 32
 Nursing Implications (Cont.)

 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. 33

 Nursing Implications (Cont.)

 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. 34

 Audience Response System Question
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. A combination of antitubercular drugs will be chosen to fight the

infection.
B. The patient will receive the drug and supportive care to help him
tolerate the antitubercular therapy.
C. The patient will remain on isolation precautions until his cough
clears.
D. There is nothing that can be done for this patient.

Copyright © 2017, Elsevier Inc. All rights reserved. 35

 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?

A. “That is a good idea. Children should not be exposed to TB.”

B. “You should give your son half of the dose you take.”
C. “Do not share any of your medications with anyone. Contact your
son’s health care provider to discuss your concerns.”
D. “Children have an immune system that makes them immune to
TB.”

Copyright © 2017, Elsevier Inc. All rights reserved. 36

 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?

A. BCG is used to prevent infection with TB for women of

childbearing age.
B. A positive result for a PPD test is indicated by redness at the site
of injection.
C. PPD is a diagnostic injection given intradermally to detect
exposure to the TB organism.
D. BCG is a vaccine injection derived from an activated strain of
Mycobacterium bovis.

Copyright © 2017, Elsevier Inc. All rights reserved. 37

 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?

A. “Because my oral contraceptives will not work while

I am taking rifampin, I will use another form of birth
control.”
B. “I will take the medication for 1 week and then stop.”
C. “I will avoid prolonged exposure to the sun.”
D. “My urine may turn a reddish color when taking
rifampin.”

Copyright © 2017, Elsevier Inc. All rights reserved. 38