Infectious Disease I Tuberculosis Courses in Therapeutics and
Infectious Disease I: Tuberculosis Courses in Therapeutics and Disease State Management Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-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. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Required Reading Namdar R, Lauzardo M, Peloquin CA. Chapter 90. Tuberculosis. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Overview (Slide 2 of 2) Risk Factors M. tuberculosis • Location and Place of Birth • Close contact with pulmonary TB patients • Ethnic minorities are at a higher risk in the United States • HIV infection is the strongest single risk factor for active TB • Previous infection with TB • Immunosuppressive Medications • Slender bacillus with a waxy outer layer • 1 to 4 μm in length • Slow growth, doubling about every 20 hours • Direct susceptibility testing involves inoculating specialized media with organisms taken directly from a concentrated, smear-positive specimen • Susceptibility testing takes 2 to 3 weeks Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 • CD 4+ 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pathophysiology (Slide 2 of 2) Primary Infection • Normally results from inhaling airborne particles that contain M. tuberculosis • Infection depends on three factors • Inoculum of M. tuberculosis organisms inhaled • Virulence of these organisms • Host’s cell-mediated immune response • Apical region of lungs are commonly infected • High oxygen availability • Poor immune response in this region • T-lymphocytes become sensitized to M. tuberculosis three weeks after start of infection • Stimulate macrophages to become bactericidal • Macrophages form granulomas to contain the organisms Reactivation Disease • Occurs within first 2 years of primary infection • Organisms within granulomas emerge and begin multiplying extracellularly • Inflammatory response produces caseating granulomas that lead to the formation of a hole (cavity) in the lungs. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Clinical Presentation (Slide 1 of 2) • Signs and Symptoms • • • Weight loss Fatigue Productive cough Fever Night sweats Frank hemoptysis • Physical Examination • Dullness to chest percussion • Rales • Increased vocal fremitus • Laboratory Tests • Elevated (WBC) count with a lymphocyte predominance • Diagnostic Considerations • Positive sputum smear • Fiber-optic bronchoscopy (if sputum tests are inconclusive and suspicion is high) • Chest Radiograph • Patchy or nodular infiltrates in the apical areas of the upper lobes or the superior segment of the lower lobes • Cavitation that may show air–fluid levels as the infection progresses Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Clinical Presentation (Slide 2 of 2) Criteria for Tuberculin Positivity by Risk Group Reaction 5 mm of Induration Reaction ≥ 10 mm of Induration Human immunodeficiency virus (HIV)-positive persons Recent immigrants (i. e. , within the last 5 years) from high-prevalence countries Recent contacts of tuberculosis (TB) case patients Injection-drug users Reaction ≥ 15 mm of Induration Persons with no risk factors for TB 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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) Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 costeffective way to ensure completion of treatment and is considered the standard of care Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: Latent Tuberculosis Infection (Slide 2 of 2) Drug Isoniazid Rifampin Interval and Duration Comments Ratinga(Evidence)b HIV− A (II) HIV+ A (II) Twice weekly for 9 monthsb, c Directly observed therapy (DOT) must be used with twice-weekly dosing B (II) Daily for 6 monthsc B (I) C (I) B (II) C (I) Daily for 9 monthsb, c In human immunodeficiency virus (HIV)-infected patients, isoniazid may be administered concurrently with nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors, or non-nucleoside reverse transcriptase inhibitors (NNRTIs) Not indicated for HIV-infected persons, those with fibrotic lesions on chest radiographs, or children c Twice weekly for 6 months DOT must be used with twice-weekly dosing Daily for 4 months Isoniazid Once weekly for 3 months and rifapentine For persons who are contacts of patients with isoniazid-resistant, rifampin-susceptible TB who B (II) cannot tolerate pyrazinamide B (III) DOT must be used with once-weekly dosing. Not recommended for the following: children <2 B (II) 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 B (II 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: Active Tuberculosis Infection (Slide 2 of 5) 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: Active Tuberculosis Infection (Slide 3 of 5) • 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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: Active Tuberculosis Infection (Slide 4 of 5), Special Populations • Tuberculous Meningitis and Extrapulmonary Disease • Pregnancy • Children are often treated with regimens similar to those used in adults for 9 months at pediatric doses • HIV Infection • Patients with renal and hepatic failure often require dosing adjustments • Treated for longer durations • Isoniazid, pyrazinamide, ethionamide, and cycloserine penetrate the cerebrospinal fluid readily • Women with TB should be cautioned against becoming pregnant because the disease poses a risk to the fetus and to the mother • For patients that are pregnant, the usual treatment is isoniazid, rifampin, and ethambutol for 9 months • Managed with chemotherapeutic regimens similar to those used in immunocompetent individuals • Treatment duration remains controversial Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
Pharmacological Treatment: Active Tuberculosis Infection (Slide 5 of 5) Link: Table on Recommended Regimens for the Concomitant Treatment of Tuberculosis and HIV Infection Link: Table on Dosing Recommendations for Adult Patients with Reduced Renal Function and for Adult Patients Receiving Hemodialysis Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
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 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
References Namdar R, Lauzardo M, Peloquin CA. Chapter 90. Tuberculosis. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved
- Slides: 23