Infectious Disease I - 16 (1) - Tuberculosis (Courses in Therapeutics and Disease State Management)

Infectious Disease I:
Tuberculosis
Courses in Therapeutics and Disease State Management
Author: Michael W. Perry PharmD, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy
http://accesspharmacy.mhmedical.com/LearningModuleGroup.aspx?id=8
Copyright © 2017 McGraw-Hill Education. All rights reserved
Learning Objectives (Slide 1 of 2)
• Identify the risk factors for TB infection and active disease.
• Design an appropriate therapeutic plan for latent tuberculosis in
immunocompetent, immunocompromised, and special patient
populations.
• Design an appropriate therapeutic plan for active tuberculosis in
immunocompetent, immunocompromised, and special patient
populations.
• Distinguish between the diagnostic tests used for patients potentially
infected with tuberculosis.
Learning Objectives (Slide 2 of 2)
• Identify the common adverse effects associated with medications used for the
treatment of tuberculosis.
• Implement an alternative therapeutic plan for patients with tuberculosis who
are experiencing adverse drug reactions or not responding to therapy.
• Implement an alternative therapeutic plan for patients with tuberculosis who
are at risk of or are experiencing clinically significant drug interactions.
• Formulate a monitoring plan for a patient being treated for latent or active TB.
• Select patients for whom therapeutic drug monitoring may be valuable and
identify the necessary laboratory monitoring parameters for patients on
antituberculosis medications.
Required Reading
Namdar R, Lauzardo M, Peloquin CA. Chapter 90. Tuberculosis.
In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds
.
Pharmacotherapy: A Pathophysiologic Approach, 9e.
New York, NY: McGraw-Hill; 2014.
Overview (Slide 1 of 2)
• Tuberculosis (TB) remains a leading infectious killer globally
• TB is caused by Mycobacterium tuberculosis, which can produce
either a silent, latent infection or a progressive, active disease
• TB is an airborne disease that is easy to spread in areas of high
population density
Overview (Slide 2 of 2)
Risk Factors M. tuberculosis
• Location and Place of Birth • Slender bacillus with a waxy outer layer
• Close contact with pulmonary TB • 1 to 4 μm in length
patients • Slow growth, doubling about every 20
• Ethnic minorities are at a higher risk hours
in the United States • Direct susceptibility testing involves
• HIV infection is the strongest inoculating specialized media with
organisms taken directly from a
single risk factor for active TB
concentrated, smear-positive specimen
• Previous infection with TB • Susceptibility testing takes 2 to 3 weeks
• Immunosuppressive Medications
Pathophysiology (Slide 1 of 2)
• M. tuberculosis is transmitted from person to person by coughing or other activities
that cause the organism to be aerosolized into droplet nuclei
• Immune Response
• CD4+ T lymphocytes are responsible/ essential to controlling M. tuberculosis infections
• Activate macrophages which engulf and kill mycobacteria
• Destroy immature macrophages that harbor M. tuberculosis but are unable to kill the invaders
• Humoral B-cell response is minimal to M. tuberculosis
• Tumor necrosis factor-α (TNF-α) and INF-γ are important cytokines involved in coordinating
the host’s cell-mediated response
• M. tuberculosis evasion of immune system
• Inhibits the fusion of lysosomes to phagosomes inside macrophages
• Lipoarabinomannan (LAM) inhibits the host immune response
Pathophysiology (Slide 2 of 2)
Primary Infection Reactivation Disease
• Normally results from inhaling airborne particles • Occurs within first 2 years of
that contain M. tuberculosis
primary infection
• Infection depends on three factors
• Inoculum of M. tuberculosis organisms inhaled • Organisms within granulomas
• Virulence of these organisms emerge and begin multiplying
• Host’s cell-mediated immune response extracellularly
• Apical region of lungs are commonly infected
• High oxygen availability
• Inflammatory response produces
• Poor immune response in this region caseating granulomas that lead to
• T-lymphocytes become sensitized to M. the formation of a hole (cavity) in
tuberculosis three weeks after start of infection the lungs.
• Stimulate macrophages to become bactericidal
• Macrophages form granulomas to contain the organisms
Clinical Presentation (Slide 1 of 2)
• Signs and Symptoms • Laboratory Tests
• Weight loss • Elevated (WBC) count with a lymphocyte
predominance
• Fatigue
• Productive cough • Diagnostic Considerations
• Positive sputum smear
• Fever
• Fiber-optic bronchoscopy (if sputum tests
• Night sweats are inconclusive and suspicion is high)
• Frank hemoptysis • Chest Radiograph
• Physical Examination • Patchy or nodular infiltrates in the apical
• Dullness to chest percussion areas of the upper lobes or the superior
segment of the lower lobes
• Rales • Cavitation that may show air–fluid levels
• Increased vocal fremitus as the infection progresses
Clinical Presentation (Slide 2 of 2)
Criteria for Tuberculin Positivity by Risk Group
Reaction 5 mm of Induration Reaction ≥10 mm of Induration Reaction ≥15 mm of Induration
Human immunodeficiency virus (HIV)-positive persons Recent immigrants (i.e., within the last 5 years) from high-prevalence Persons with no risk factors for TB
countries
Recent contacts of tuberculosis (TB) case patients Injection-drug users
Fibrotic changes on chest radiograph consistent with Residents and employeesa of the following high-risk congregate settings:
prior TB prisons and jails, nursing homes and other long-term care facilities for the
elderly, hospitals and other healthcare facilities, residential facilities for
patients with acquired immunodeficiency syndrome (AIDS), homeless
shelters
Patients with organ transplants and other •Mycobacteriology laboratory personnel

immunosuppressed patients (receiving the equivalent •Persons with the following clinical conditions that place them at high risk:
of ≥15 mg/day of prednisone for 1 month or more)b silicosis, diabetes mellitus, chronic renal failure, some hematologic
disorders (e.g., leukemias and lymphomas), other specific malignancies
(e.g., carcinoma of the head or neck and lung), weight loss of ≥10% of
ideal body weight, gastrectomy, jejunoileal bypass
•Children younger than 4 years of age or infants, children, and adolescents
exposed to adults at high risk
a
For persons who are otherwise at low risk and who are tested at the start of employment, a reaction of ≥15 mm induration is considered positive.
b
Risk of TB for patients treated with corticosteroids increases with higher dose and longer duration
Goals of Therapy
• Rapid identification of a new TB case
• Initiation of specific anti-TB treatment
• Prompt resolution of the signs and symptoms of disease
• Achievement of a noninfectious state in the patient, thus ending
isolation
• Adherence to the treatment regimen by the patient
• Cure of the patient as quickly as possible (generally at least 6 months
of treatment)
General Approach to Treatment
• Drug treatment is the cornerstone of TB management
• Latent TB can be managed with monotherapy
• Active TB is treated with a minimum of two medications and up to four simultaneously
• Duration of treatment depends on several variables
• Condition of the host
• Extent of disease
• Presence of drug resistance
• Tolerance of medications
• Duration of therapy can last 6 months to 3 years of treatment for multidrug
resistant cases
• Directly observed therapy (DOT) by a healthcare worker is a cost-effective way
to ensure completion of treatment and is considered the standard of care
Nonpharmacological Treatment
• Prevent the spread of TB
• Locate where TB has already spread using contact investigation
• Replenish the weakened (consumptive) patient to a state of normal
weight and well-being
• Nutritional Support
• Rehabilitation
• Surgical intervention to remove necrotic lung tissue
Pharmacological Treatment:
Latent Tuberculosis Infection (Slide 1 of 2)
• Isoniazid is the preferred drug for treating LTBI
• Treatment duration 9 months
• Isoniazid adult doses are usually 300 mg daily (5 to 10 mg/kg of body
weight)
• Rifampin can be used when isoniazid resistance is suspected or when
the patient cannot tolerate isoniazid
• Treatment duration is 4 months
• 600 mg daily
• Rifabutin might be substituted for rifampin for patients at high risk
of drug interactions
• Treatment duration is 4 months
• 300 mg daily
Latent Tuberculosis Infection (Slide 2 of 2)
Drug Interval and Duration Comments Ratinga(Evidence)b
HIV− HIV+
Isoniazid Daily for 9 monthsb,c In human immunodeficiency virus (HIV)-infected patients, isoniazid may be administered A (II) A (II)
concurrently with nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors, or
non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Twice weekly for 9 monthsb,c Directly observed therapy (DOT) must be used with twice-weekly dosing B (II) B (II)
Isoniazid Daily for 6 monthsc Not indicated for HIV-infected persons, those with fibrotic lesions on chest radiographs, or B (I) C (I)
children
Twice weekly for 6 monthsc DOT must be used with twice-weekly dosing B (II) C (I)
Rifampin Daily for 4 months For persons who are contacts of patients with isoniazid-resistant, rifampin-susceptible TB who B (II) B (III)
cannot tolerate pyrazinamide
Isoniazid Once weekly for 3 months DOT must be used with once-weekly dosing. Not recommended for the following: children <2 B (II) B (II
and rifapentine years old, HIV/AIDS patients taking antiretroviral treatment, isoniazid- or rifampin-resistant
strains, pregnant women or women expecting to become pregnant within the 12-week
regimen
a
Strength of recommendation: A, preferred; B, acceptable alternative; C, offer when A and B cannot be given.
b
Quality of evidence: I, randomized clinical trial data; II, data from clinical trials that are not randomized or were conducted in other populations; III, expert opinion.
c
Recommended regimen for children younger than 18 years of age.
Data from Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep 2000;49(RR-6):31
Active Tuberculosis Infection (Slide 1 of 5)
• The treatment of active TB requires the use of multiple drugs
• Isoniazid and rifampin are the major backbone of therapy
• Other medications are utilized for specific roles
• M. tuberculosis is either very susceptible or very resistant to a given drug
• Drug susceptibility testing should be completed to aid in medication selection over the long
course of treatment
• If individual patient drug susceptibility testing is not available, susceptibility information from
regional or suspect source case may be used
• The standard TB treatment regimen is isoniazid, rifampin, pyrazinamide,
and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months, a
total of 6 months of treatment
• There is no standard regimen for MDR-TB
Link: Treatment Algorithm for Tuberculosis
Link:
Table on Drug Regimens for Culture-Positive Pulmonary Tuberculosis
Caused by Drug-Susceptible Organisms
Link: Table on Dosesa of Antituberculosis Drugs for Adults and

Childrenb,c
• Drug resistance should be considered in the following situations:
• Patients who have received prior therapy for TB
• Patients from areas with a high prevalence of resistance (South Africa, Dominican
Republic, Peru, Southeast Asia, the Baltic countries, and the former Soviet states)
• Patients who are homeless, institutionalized, IV drug abusers, or infected with HIV
• Patients who still have AFB-positive sputum smears after 1 to 2 months of therapy
• Patients who still have positive cultures after 2 to 4 months of therapy
• Patients who fail treatment or relapse after treatment
• Patients known to be exposed to MDR-TB cases
• TB specialists should be consulted regarding cases of MDR-TB
Active Tuberculosis Infection (Slide 4 of 5),
Special Populations
• Tuberculous Meningitis and • Pregnancy
Extrapulmonary Disease • Women with TB should be
• Treated for longer durations
cautioned against becoming
• Isoniazid, pyrazinamide, ethionamide,
and cycloserine penetrate the cerebrospinal pregnant because the disease poses a
fluid readily risk to the fetus and to the mother
• Children are often treated with regimens • For patients that are pregnant, the
similar to those used in adults for 9 months usual treatment
at pediatric doses is isoniazid, rifampin,
• HIV Infection and ethambutol for 9 months
• Managed with chemotherapeutic regimens • Patients with renal and hepatic
similar to those used in immunocompetent
individuals failure often require dosing
• Treatment duration remains controversial adjustments
Link:
Table on Recommended Regimens for the Concomitant Treatment of Tu
berculosis and HIV Infection
Link:
Table on Dosing Recommendations for Adult Patients with Reduced Re
nal Function and for Adult Patients Receiving Hemodialysis
Clinical Outcomes
• When a patient’s sputum smears convert to a negative, the risk of the patient infecting
others is greatly reduced, but it is not zero
• Resolution of presenting signs and symptoms
• Monitor for nonadherence to prescribed drug therapy
• Monitor for adverse effects of prescribed therapy
• Baseline and periodic laboratory monitoring of serum chemistries
• BUN
• Creatinine
• Aspartate transaminase
• Alanine transaminase
• Complete blood count with platelets
• All patients diagnosed with TB should be tested for HIV infection.
• Link: Table on Antituberculosis Drug Monitoring
Summary
• TB is caused by Mycobacterium tuberculosis, which can produce either a silent,
latent infection or a progressive, active disease
• The typical patient presents with weight loss, fatigue, productive cough, fever,
and night sweats
• Drug treatment is the cornerstone of TB management
• Latent TB can be managed with Isoniazid monotherapy
• Active TB is treated with a minimum of two medications and up to four simultaneously
• The standard TB treatment regimen is isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months,
followed by isoniazid and rifampin for 4 months, a total of 6 months of treatment
• There is no standard regimen for MDR-TB
• Duration of therapy can last 6 months to 3 years of treatment for multidrug
resistant cases
References
Namdar R, Lauzardo M, Peloquin CA. Chapter 90. Tuberculosis.
In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds
.
Pharmacotherapy: A Pathophysiologic Approach, 9e.
New York, NY: McGraw-Hill; 2014.

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Infectious Disease I:

Patients with organ transplants and other •Mycobacteriology laboratory personnel

Link: Treatment Algorithm for Tuberculosis

Link: Table on Dosesa of Antituberculosis Drugs for Adults and

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