Tuberculosis paper

Tuberculosis Catherine M. Oliphant, PharmD ABSTRACT Tuberculosis (TB) resulted in 1.3 million deaths and 8.6 million new cases of active TB worldwide in 2012. Clinical manifestations of TB include fever, night sweats, weight loss, and cough. Latent infection is established by a positive tuberculin skin test or interferon- g-release assay. Active TB disease is diagnosed by clinical, radiographic, and laboratoryﬁndings. Latent infection treatment is recommended in at-risk populations. The standard initial regimen for active disease includes rifampin, isoniazid, pyrazinamide, and ethambutol. Health-care providers are encouraged to consult with a TB specialist for assistance in the management of individuals with suspected or conﬁrmed TB.

Keywords:acid-fast bacilli, ethambutol, interferon- g-release assay, isoniazid, latent TB, multidrug-resistant TB, pyrazinamide, rifampin, tuberculin skin test, tuberculosis 2015 Elsevier, Inc. All rights reserved. T uberculosis is one the most transmissible in- fectious diseases in the world. It is a signiﬁ- cant cause of infectious disease‒related death throughout the world (ranking second only to HIV) and ranks within the top 15 causes of death world- wide. 1,2 Tuberculosis (TB) is caused byMycobacterium tuberculosis(MTb), an acid-fast bacillus bacteria. HIV has contributed to the resurgence of TB worldwide.

In addition, the emergence of drug-resistant TB has increased the burden of TB disease. EPIDEMIOLOGY One third of the world’s population is infected with TB. 3In 2012, there were 8.6 million new cases of active TB and approximately 1.3 million TB-related deaths worldwide. 2-4 In the United States, in 2012, 9,945 TB cases (3.2 cases per 100,000 persons) were reported; this was the lowest number of cases since reporting began in 1953. 3The number of TB cases in the US has decreased since the 1992 resurgence peak.

In the US, the majority of TB cases occur among foreign-born individuals. In 2012, the case rate among foreign-born individuals was 11 times higher than among US-born individuals. 3,5-7 In addition, immunocompromised individuals are at greater risk for active TB (TB disease). HIV-infected individuals who also have latent TB infection are 21 to 34 times more likely to develop active TB. 3,4 Throughout the world, the number the number of TB cases per year is also slowly declining (between 1992 and 2012, the death rate decreased by 45%). 2,4 The World Health Organization has a goal to reverse the spread of TB by 2015. 4In 2012, Asia had the largest number of new TB cases (60% of new cases).

However, sub-Saharan Africa had the highest proportion of new cases per capita (255 per 100,000).

Other countries with high rates of TB include India, China, and the Russian Federation. Approximately 80% of TB cases in 2012 occurred in only 22 countries. 2,4,6 PATHOPHYSIOLOGY Once inhaled, the majority of droplet nuclei con- taining MTb are trapped in the upper airways and expelled by the cilia. The bacteria that escape expulsion reach the alveoli and, initially, multiply unopposed by host defense mechanisms. Cell- mediated immunity eventually kicks in to activate T lymphocytes and macrophages. The macrophages surround the MTb forming granulomas that limit replication and spread of the MTb. It is estimated that it takes 4 to 12 weeks for a delayed hypersensitivity reaction to occur and it is at this point that the skin test conversion can occur. Granulomas may later liquefy, resulting in reactivation. In individuals with impaired cell-mediated immunity, the disease may www.npjournal.orgThe Journal for Nurse Practitioners - JNP 87 initially present as primary pulmonary TB or, later on, as reactivation disease. 8-10 TRANSMISSION Latent TB infection (LTBI) occurs after the cell- mediated immune response, where progression is halted and the bacteria are contained in localized lesions. At this point, the individual is asymptomatic and noninfectious. Individuals with active pulmonary TB disease are contagious. TB is transmitted via droplet nuclei primarily from patients with positive acid-fast bacilli (AFB) smears. 7-10 CLINICAL PRESENTATION LTBI is not associated with clinicalﬁndings and is not contagious. However, individuals with LTBI may develop TB disease. In the US, more than 80% of active TB cases are the result of reactivation. 11 It is estimated that 10% of individuals with untreated LTBI will reactivate to active disease during their lifetime; this risk is highest during theﬁrst 2 years after infection. If an individual with LTBI becomes infected with HIV, that risk increases to 5% to 12% per year. If an HIV-infected individual acquires LTBI, the risk of active disease within 2 years is up to 50%, depending on the status of the immune system. 8,9,11 Pulmonary disease can be classiﬁed as primary or reactivation. Primary pulmonary TB symptoms are generally mild and patients are relatively asymptom- atic. Physical examinationﬁndings are unremarkable; lymphadenopathy may be present as well as hilar adenopathy on chest radiography. Classic symptoms of reactivation disease include fever, night sweats, weight loss, anorexia, fatigue, and cough (initially nonproductive but progresses to productive with purulent sputum), with or without hemoptysis.

Physical examinationﬁndings are nonspeciﬁc but may include rales or dullness to percussion. Chest radiography may reveal inﬁltrates in the apical and posterior segments of the upper lobes. Cavitation may also be visible on chest radiography. However, not all patients will have traditional chest radiography ﬁndings and may have atypical (lower lobe inﬁltrates, hilar adenopathy) or normal radiographicﬁndings. 7-10 Before the HIV epidemic, the majority of TB cases were pulmonary, with the remaining 15% beingextrapulmonary. However, in advanced HIV infec- tion, extrapulmonary TB disease with or without pulmonary disease is more common. The risk increases as immune function decreases due to the immune system’s inability to contain the MTb. Extrapulmo- nary disease may occur at any site, including bones, joints, lymph nodes, central nervous system, peritoneal space, pleura, and pericardium. Disseminated TB may also occur secondary to poor host defenses and is referred to as miliary TB. Miliary TB occurs more commonly in children and immunocompromised individuals. This form of TB may be rapidly fatal as patients can present with severe disease (ie, septic shock and acute respiratory distress syndrome 7-11 ). DIAGNOSIS Screening and diagnosis are important strategies in identifying persons with MTb infection and disease.

The screening tests cannot distinguish between infection (LTBI) and disease (active TB). Until recently, the tuberculin skin test (TST) was the only screening test to identify LTBI. The interferon- g-release assays (IGRA) can also detect latent tuberculosis. Diagnosis of active TB is based on clinical, laboratory, and radiographicﬁndings.

LATENT TB Tuberculin Skin Test The TST, also known as the Mantoux test, is an intradermal injection of 0.1 mL of 5 tuberculin units of puriﬁed protein derivative (PPD) into the dorsal or volar surface of the forearm. This screening test measures cell-mediated immunity via a delayed-type hypersensitivity to the PPD. Interpretation of the test is done 48 to 72 hours after administration. The in- jection site is examined by a trained health-care provider for induration, not erythema. 7,9-11 Interpretation of the skin reaction is based on induration size, not erythema. Induration between 5 and 15 mm is considered positive for speciﬁc risk groups (Table 1). Individuals who have a positive TST are at increased risk of developing active TB disease. These individuals should receive drug therapy for LTBI. In an individual with a negative TST in the previous 2 years with a repeat positive TST, an increase of 10 mm is predictive of recent MTb infection. 7,9-12 The Journal for Nurse Practitioners - JNP Volume 11, Issue 1, January 2015 88 The tuberculin PPD is a mixture of mycobacteria antigens, not speciﬁc to MTb. Therefore, reactivity of the PPD may be due to MTb, other non- tuberculous bacteria, or bacillus Calmette-Guerin (BCG) vaccine (false positive). If the PPD is positive in a person who has received the BCG vaccine, interpretation may be difﬁcult; if the person was recently exposed to MTb, or is at high risk, is it likely to represent infection with MTb. False negative re- sults may also occur if the TST was inappropriately administered, in immunocompromised patients, and if the TST was administered too soon after exposure.

Reactivity to infection is estimated at 2 to 12 weeks after exposure to MTb (host cell‒mediated immunity must respond to the infection). If the individual wasrecently exposed and has a negative TST, the TST should be repeated 8 to 12 weeks after exposure. 7,9-11 The IGRA The IGRA is an alternative to the TST and are more speciﬁc than the TST. This type of assay require a single blood test so a repeat visit is not necessary for diagnostic evaluation. An IGRA can measure the release of interferon- gin the blood after T-cell stimulation by MTb antigens. Currently, two IGRAs are available (QuantiFERON-TB Gold and T-SPOT). 6,7,13 The results of both of these assays are reported as positive, negative, indeterminate, or borderline, as well as quantitatively. Test results are available in 16 to 24 hours as compared with the 48 to 72 hours required for the TST. In addition, results are not confounded by previous BCG vaccination or most other nontuberculous mycobacteria. However, they are considerably more expensive than TSTs. These assays are not recommended for use in children<5 years old. 6,7,13 Patients with a positive TST or IGRA should undergo further testing to rule out active TB. ACTIVE TB Active TB should be considered when clinical and risk assessmentﬁndings indicate a strong suspicion for TB. The patient should have a chest radiograph performed; abnormalﬁndings on chest radiography may suggest TB, but are not diagnostic. If abnormal chest radiographﬁndings are present, a sputum smear for the detection of AFB is performed to aid in the diagnosis of active TB. 6-10 The Centers for Disease Control and Prevention (CDC) recommends that three sputum specimens on 3 consecutive days be sent for AFB smear. 10 The results of an AFB smear are usually available within 24 hours. 7-10 Newer, rapid diagnostic tests are available for the detection of MTb. The tests are based on nucleic acid ampliﬁcation (NAA); they amplify nucleic acid se- quences speciﬁc for MTb, yielding results in approximately 2 hours. In addition, these tests can detect low concentrations of MTb and do not require live or viable organisms for detection. NAA tests are highly sensitive and speciﬁc. Currently, these tests are typically used in conjunction with AFB smearﬁnd- ings; a positive NAA test and AFB smear is highly Table 1. Candidates for the Treatment of Latent TB Infection—Based on TB Skin Test or IGRA Results 7-11 Positive TST Reaction of 5mm or Positive IGRA ResultPositive TST Reaction of 10 mm or Positive IGRA ResultPositive TST Reaction of 15 mm or Positive IGRA Result HIV infection Recent contact with an active TB case Fibrotic changes on chest X-ray consistent with previous TB Organ transplant recipients Persons receiving immunosup- pressant therapy a Recent immigrants (within 5 years) from high- prevalence countries Injection drug users Residents and employees of high-risk facilities b Persons with chronic conditions c Children 4 years of age and younger and adolescents exposed to adults at high risk Mycobacteriology lab personnel Individuals with no known risk factors IGRA¼interferon- g-release assay; TB¼tuberculosis; TST¼tuberculin skin test. aReceiving the equivalent of>15 mg/day prednisone for 1 month, tumor necrosis factor- aantagonists, or chemotherapeutic agents. bPrisons, nursing homes, long-term care facilities, hospitals, other health-care facilities, homeless shelters.

cDiabetes, chronic renal failure, silicosis, leukemia, lymphoma, cancers of head/ neck/lung, or weight loss 10% of ideal body weight.

www.npjournal.orgThe Journal for Nurse Practitioners - JNP 89 indicative of active TB, whereas with smear negative and NAA positive it is likely that the patient has TB and it is too early in the disease to detect on AFB smear. Of note, the NAA test may remain positive after completion of treatment. 6,7,13,14 CULTURE Sputum culture is the standard method for diagnosing active TB. Solid culture (conventional technique) takes 4 to 6 weeks as MTb is a slow-growing or- ganism. Culture in a liquid media (ie, BACTEC) results in more rapid growth and allows detection in 1 to 3 weeks. Subsequent antimicrobial susceptibility testing is then performed, which generally takes an additional 2 to 4 weeks. 6,7,10 PATIENT REFERRAL Individuals with suspected or conﬁrmed tuberculosis should be referred to a TB specialist (ie, infectious disease or pulmonology) for initial management. In addition, the patient should be seen by a TB specialist during and/or after completion of therapy if not responsive to therapy or shows worsening or relapse after completion of therapy.

The CDC recommends that all patients with LTBI, active TB, suspected TB based on clinical ﬁndings, and those identiﬁed as a contact of a person with TB disease be screened for HIV. The rationale for this recommendation is that HIV infection is the greatest risk factor for progression from LTBI to active disease. TB can be associated with high mor- tality in this population. 15,16 TREATMENT The decision to initiate therapy is based on clinical, radiographic, and laboratoryﬁndings. LTBI may be treated with monotherapy, but combination therapy must be used to treat active TB. The goals of drug therapy for active disease are to cure the individual patient and minimize transmission of TB to others.

Most patients with TB can be cured with strict adherence to their prescribed drug regimens. Directly observed therapy (DOT) is a method to ensure pa- tient adherence and completion of therapy. DOT is where patients are observed directly as they ingest each dose of TB medication. The CDC states that DOT is the preferred core management strategy fortreatment of TB disease and, if resources allow, LTBI treatment. DOT can reduce the risk of drug resis- tance, treatment failure, or relapse. Other measures that may improve adherence and maximize the likelihood of completion of therapy include social services, treatment incentives/enablers, housing assistance, and treatment of substance abuse. 8-10 Of the available agents to treat TB, isoniazid, rifampin, ethambutol, and pyrazinamide are consid- eredﬁrst-line anti-TB drugs. Second-line drugs (cycloserine, ethionamide, streptomycin, amikacin, capreomycin,p-aminosalicylic acid, levoﬂoxacin, and moxiﬂoxacin) are used to treat TB caused by drug- resistant organisms or in those who are intolerant to ﬁrst-line agents. 8-10,17 Combination therapy with four drugs is required for initial therapy in active TB to minimize drug resistance and act on the various populations of mycobacterium causing disease. Three sub- populations of MTb can exist during infection and multiple agents are required to eradicate these various populations. Treatment with a single drug can lead to the development of resistance to that agent as can the addition of a single drug to a failing drug regimen.

When two or more drugs to which susceptibility has been demonstrated are given together, the emer- gence of resistant MTb is minimized. Isoniazid and rifampin are generally the backbone of therapy and are most effective at preventing the emergence of drug resistance. 8-10,17 Providers are encouraged to contact the local health department if they are involved in the care of a TB-infected patient. DOT may be performed through the local health department or they can refer the provider to appropriate resources for collabora- tion in the care of TB-infected patients. Latent Infection Treatment for latent infection is recommended for individuals at increased risk of developing active TB (Table 1). Active TB infection must be excluded by clinical and radiographic studies before treatment for LTBI can be initiated. 8-11 Monotherapy can be used for patients with latent infection. Treatment of LTBI reduces an individual’s lifetime risk of active TB from about 10% to 1%.Table 2lists the treatment options for LTBI. According to the CDC, isoniazid is the The Journal for Nurse Practitioners - JNP Volume 11, Issue 1, January 2015 90 preferred agent for treating LTBI. A 9 month regimen of isoniazid is the preferred one, although the 6 month regimen may also be considered.

However, twice-weekly regimens and short-course therapy may be considered; these regimens are not indicated in HIV-infected persons and must be administered via DOT. Concomitant administration of pyridoxine (vitamin B 6) with isoniazid should be considered in alcoholics, pregnant women, and those with a poor diet. Pyridoxine is given to reduce the risk of peripheral neuropathies and other central nervous system effects. 8-11 Isoniazid plus rifapentine for 3 months demonstrated equal efﬁcacy to isoniazid alone in non‒HIV-infected adults in countries with a low incidence of TB. 12 Rifampin alone may beconsidered when isoniazid resistance is suspected or if the patient cannot tolerate isoniazid. Regimens containing rifampin or rifapentine are associated with signiﬁcant drug interactions. 7-12 Active Infection Standard TB treatment regimens consist of four drug regimens consisting of a 2 month initial phase fol- lowed by a continuation phase of 4 or 7 months.

Table 3describes recommended active TB regimens.

Table 4lists dosing recommendations. The initial phase is continued until susceptibility results are available. Combination therapy is always necessary for the treatment of active TB. The standard initial TB regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol. If the isolate is Table 2. Latent TB Infection Treatment Regimens (CDC Recommendations) 7-11 Treatment Regimen Adult DoseInterval and Duration Isoniazid a 5 mg/kg (300 mg max dose)Daily 9 months Isoniazid b 15 mg/kg (900 mg max dose)Twice weekly 9 months Isoniazid 5 mg/kg (300 mg max dose)Daily 6 months Isoniazid b 15 mg/kg (900 mg max dose)Twice weekly 6 months Isoniazid plus rifapentine b,c Isoniazid 900 mg, rifapentine 900 mgOnce weekly 3 months Isoniazid plus rifampinIsoniazid 300 mg, rifampin 600 mgDaily 3 months Isoniazid plus rifampin b Isoniazid 900 mg, rifampin 600 mgTwice weekly 3 months Rifampin d 10 mg/kg (600 mg max dose)Daily 4 months aPreferred/standard regimen.bUse directly observed therapy.cNot recommended for HIV-infected individuals taking antiretroviral agents, pregnant women, or children<2 years of age.

dConsider when isoniazid resistance is suspected or in patients intolerant of isoniazid. Table 3. Treatment Regimes for Drug-susceptible pulmonary TB 7-10 Initial Phase Continuation Phase Medication RegimenInterval and DurationMedication RegimenInterval and Duration Isoniazid, rifampin, pyrazinamide, ethambutol7 days/week 8 weeks; or 5 / week 8 weeksIsoniazid, rifampin Isoniazid, rifapentine7 days/ week or 5 days/week or twice weekly 18 weeks Once weekly 18 weeks Isoniazid, rifampin, pyrazinamide, ethambutol7 days/week 2 weeks then 2 /week 6 weeks; or 5 days/week for 2 weeks then 2 /week for 6 weeksIsoniazid, rifampin Isoniazid, rifapentineTwice weekly 18 weeks Once weekly 18 weeks Isoniazid, rifampin, pyrazinamide, ethambutol3 /week for 8 weeksIsoniazid, rifampin3 times/ week 18 weeks Isoniazid, rifampin, ethambutol7 days/week or 5 /week for 8 weeksIsoniazid, rifampin7 days/ week or 5 days/week or twice weekly 31 weeks TB¼tuberculosis. www.npjournal.orgThe Journal for Nurse Practitioners - JNP 91 susceptible to isoniazid and rifampin, pyrazinamide and ethambutol may be discontinued. DOT is recommended if two- or three-times-per-week therapy is used. 7-10,17 Sputum specimens should be obtained at least once per month until two consecutive smears and cultures are negative. If sputum cultures remain positive after 2 months of therapy, the continuation Table 4. First-line TB Medications for Adults 7-10 Medication Dose Interval Adverse Effects Drug Interactions Monitoring Isoniazid 5 mg/kg (300 mg max) 15 mg/kg (900 mg max) Daily 2 /week, 3 /week, or 5 / weekPeripheral neuropathy, hepatotoxicity, central nervous system effects (dizziness, lethargy, memory impairment, slurred speech), nausea, vomiting, rashCYP450 inhibitor (1A2, 2A6, 2C19, 2C9, 2D6, 2E1, 3A4)Baseline and periodic hepatic tests Rifampin 10 mg/kg (600 mg max) Daily, 2 / week, or 3 /weekHepatotoxicity, nausea, vomiting, diarrhea, rash, ﬂulike syndrome, red- orange discoloration of bodyﬂuids (urine, sweat, tears)CYP450 inducer (1A2, 2A6, 2B6, 2C19, 2C8, 2C9, 3A4, and P- glycoprotein)Baseline and periodic hepatic tests, CBC Rifabutin 5 mg/kg (300 mg max) Daily, 2 / week, or 3 /weekSimilar to rifampin, uveitisCYP450 inducer (3A4); substrate of CYP1A2 and CYP3A4Baseline and periodic hepatic tests, CBC Rifapentine 10 mg/kg (600 mg max) 5 /weekSimilar to rifampin CYP450 inducer (2C8, 2C9, and 3A4)Baseline and periodic hepatic tests, CBC Pyrazinamide Based on lean body weight:

40-55 kg: 1,000 mg 56-75 kg: 1,500 mg >76 kg: 2,000 mg DailyHyperuricemia, nausea, vomiting, arthralgia, malaise, hepatotoxicity No clinically signiﬁcant interactionsPeriodic hepatic tests, serum uric acid 40-55 kg: 2,000 mg 55-75 kg: 3,000 mg >76 kg: 4,000 mg 2 /week 40-55 kg: 1,500 mg 56-75 kg: 2,500 mg >76 kg: 3,000 mg 3 /week Ethambutol Based on lean body weight:

40-55 kg: 800 mg 56-75 kg: 1,200 mg >76 kg: 1,600 mg DailyOptic neuritis, peripheral neuritis, hyperuricemia, cutaneous reactionsNo clinically signiﬁcant interactionsBaseline and monthly visual acuity and color discrimination; baseline and periodic renal, hepatic, and CBC tests 40-55 kg: 2,000 mg 56-75 kg: 2,800 mg >76 kg: 4,000 mg 2 /week 40-55 kg: 1,200 mg 56-75 kg: 2,000 mg >76 kg: 2,400 mg 3 /week CBC¼complete blood count; TB¼tuberculosis. The Journal for Nurse Practitioners - JNP Volume 11, Issue 1, January 2015 92 phase should be extended to 7 months and suscep- tibility testing should be repeated to evaluate for resistance. If cultures remain positive after 4 months of therapy, the duration should be extended and drug-resistant TB should be considered. 7-10 DRUG-RESISTANT TB Drug-resistant MTb may be classiﬁed as primary or acquired. Primary resistance occurs in patients without a history of previous TB therapy. Risk factors for pri- mary resistance include residence/travel to a country with a high prevalence of resistant TB or exposure to a patient with active drug-resistant TB disease. 7-10 Acquired resistance occurs in patients receiving (or who have received) therapy for TB disease.

Multidrug-resistant TB (MDR-TB) includes iso- lates that are resistant to at least isoniazid and rifampin, the two most potent TB drugs. Extensively drug-resistant TB (XDR-TB) includes isolates that are resistant to isoniazid, rifampin, anyﬂuo- roquinolone and at least one of three injectable second-line drugs (ie, amikacin, kanamycin, or capreomycin). In 2011, 630,000 cases of MDR-TB occurred; it is estimated that 9% of these MDR-TB isolates are actually XDR-TB isolates. MDR-TB has been reported in 84 countries; India and China have the highest numbers of cases, but the Russian Federation has the highest rates per 100,000 people.

Mortality rates associated with MDR-TB exceed 10% and rates associated with XDR-TB have been described as 70%. 6,7,18-21 Treatment options for MDR-TB and XDR-TB are limited, complicated, and associated with more adverse effects than regimens for susceptible TB.

Drug-resistant TB cases are often resistant to the most potent TB drugs (ﬁrst-line agents) and second-line agents must be utilized. Data are limited on the most appropriate drug therapy combinations and duration of therapy. 17,19-22 Bedaquiline fumarate (Sirturo) was approved in December 2012 for the treatment of drug-resistant TB.

23 Currently, resistant MTb cases are treated with four or more drugs for 12 months to 2 years, depending on how resistant the MTb is and the patient’s underlying immune status. All patients with resistant TB should be referred to a TB specialist for therapy recommendations and follow-up. In addition, alltherapy should be administered daily via DOT. 6,17,23,24 MONITORING Patients receiving therapy for TB need to be monitored for response to therapy, adverse effects, and adherence to their drug therapy regimen (Table 4). Serum chemistries evaluating renal and liver function should be performed at baseline and periodically throughout the course of therapy in those at increased risk of toxicity (advanced age, pregnancy, alcohol abuse, concomitant hepatitis B or C). Hepatotoxicity should be considered when transaminase (aspartate transaminase, alanine transaminase) levels exceedﬁve times the upper limit of normal; transaminase levels exceeding three times the upper limit of normal in conjunction with nausea, vomiting, and jaundice; or if total bilirubin is>3 mg/dL. If hepatotoxicity occurs, the offending agents are generally discontinued. 7-10 Adverse effects are common in patients receiving TB therapy. Hepatotoxicity is the most signiﬁcant adverse effect. Theﬁrst-line agents are associated with adherence-limiting adverse effects, which should be addressed with patients before initiation of therapy (Table 4). In addition, many of the commonly used TB drugs are associated with signiﬁcant drug interactions (which can be problematic in HIV-treated patients or those taking other medications); isoniazid is a cytochrome P450 (CYP450) inhibitor and rifampin is a CYP450 inducer. Drug interactions should be evaluated in patients taking concomitant medications (Table 4).

Patient adherence must be routinely assessed because TB is almost always curable if patients take their medications as prescribed. Nonadherence can lead to drug failure, the emergence of resistant MTb, increased transmission of TB, and increased morbidity and mortality. Pill counts can be done for those patients without DOT. 8,9 SUMMARY TB is an important disease and major cause of death worldwide. Prevention is vital for eradication of this infectious condition. Public health efforts are aimed at prevention and control. Identiﬁcation of patients www.npjournal.orgThe Journal for Nurse Practitioners - JNP 93 with TB is crucial to minimize the spread of TB to others. Drug therapy for the management of latent infection and active disease is necessary to control the spread of TB. The emergence of drug-resistant TB poses challenges to clinicians with regard to appropriate treatment regimens and duration of therapy.

References 1. World Health Organization. The top 10 causes of death. Updated May 2014.

http://www.who.int/mediacentre/factsheets/fs310/en/index2.html/. Accessed June 26, 2014.

2. World Health Organization. Global tuberculosis report.http://www.who.int/tb/ publications/global_report/gtbr13_main_text.pdf?ua¼1/. 2013. Accessed June 26, 2014.

3. Centers for Disease Control and Prevention. Tuberculosis (TB): data and statistics.http://www.cdc.gov/tb/statistics/default.html/. March 7, 2014.

Updated April 23, 2014. Accessed June 26, 2014.

4. World Health Organization. Tuberculosis.http://www.who.int/mediacentre/ factsheets/fs104/en/. Reviewed March 2014. Accessed June 26, 2014.

5.Keshavjee S, Farmer PE. Tuberculosis, drug resistance, and the history of modern medicine.N Engl J Med.2012;376(10):931-936.

6.Zumla A, Raviglione M, Hafner R, et al. Tuberculosis.N Engl J Med.

2013;368(8):745-755.

7.Sia IG, Wieland ML. Current concepts in the management of tuberculosis.

Mayo Clin Proc.2011;86(4):348-361.

8. Centers for Disease Control and Prevention. Core curriculum on tuberculosis:

what the clinician should know.http://www.cdc.gov/tb/education/corecurr/ default.htm/. Updated June 21, 2013. Reviewed June 21, 2013. Accessed May 28, 2014.

9. Centers for Disease Control and Prevention. Self-study modules on tuberculosis.http://www.cdc.gov/tb/education/ssmodules/default.htm/.

Reviewed July 1, 2012. Updated April 21, 2014. Accessed June 23, 1014.

10.Centers for Disease Control and Prevention. Treatment of tuberculosis, American Thoracic Society, CDC, and Infectious Diseases Society of America.

MMWR Morb Mortal Wkly Rep.2003;52(RR-11):1-77.

11.Horsburgh CH, Rubin EJ. Latent tuberculosis infection in the United States.

N Engl J Med.2011;364(15):1441-1448.

12.Sterling TR, Villarino ME, Borisov AS, Shang N, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection.N Engl J Med.

2011;365(23):2155-2166.

13.Centers for Disease Control and Prevention. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010.MMWR Morb Mortal Wkly Rep.2010; 59(RR-5):1-25.14.Centers for Disease Control and Prevention. Updated guidelines for the use of nucleic acid ampliﬁcation tests in the diagnosis of tuberculosis.MMWR Morb Mortal Wkly Rep.2009;58(RR-01):7-10.

15. Centers for Disease Control and Prevention. Recommendations for human immunodeﬁciency virus (HIV) screening in tuberculosis.http://www.cdc.gov/ tb/publications/factsheets/testing/HIVscreening.htm/. Updated September 1, 2012. Reviewed September 1, 2012. Accessed June 26, 2014.

16.Centers for Disease Control and Prevention. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents.

MMWR Morb Mortal Wkly Rep.2009;58:1-198.

17.The Medical Letter, Inc. Drugs for tuberculosis.Med Lett.2012; 10(116):29-36.

18.Fauci AS; NIAID Tuberculosis Working Group. Multidrug-resistant and extensively drug-resistant tuberculosis; the National Institute of Allergy and Infectious Diseases Research agenda and recommendations for priority research.J Infect Dis.2008;197:1493-1498.

19.Gandhi NR, Nunn P, Dheda K, et al. Multidrug-resistant and extensively drug- resistant tuberculosis: a threat to global control of tuberculosis.Lancet.

2010;375(9728):1830-1843.

20. TB Alliance. MDR-TB XDR-TB.http://www.tballiance.org/why/mdr-xdr.php/.

2014. Accessed July 7, 2014.

21. World Health Organization. Multidrug-resistant tuberculosis (MDR-TB). 2012.

http://www.who.int/tb/challenges/mdr/mdr_tb_factsheet.pdf?ua¼1/.

22.Caminero JA, Sotgui G, Zumla A, et al. Best drug treatment for multidrug- resistant and extensively drug-resistant tuberculosis.Lancet Infect Dis.

2010;10(9):621-629.

23.Centers for Disease Control and Prevention. Provisional CDC guidelines for the use and safety monitoring of bedaquiline fumarate (Sirturo) for the treatment of multidrug-resistant tuberculosis.MMWR Morb Mortal Wkly Rep.

2013;62(RR-9):1-16.

24. Centers for Disease Control and Prevention. Multidrug-resistant tuberculosis (MDR TB).http://www.cdc.gov/tb/publications/factsheets/drtb/ mdrtb.htm/. Updated July 7, 2012. Reviewed July 1, 2012. Accessed July 7, 2014. Catherine M. Oliphant, PharmD is an associate professor of pharmacy practice at the College of Pharmacy at Idaho State University in Meridian, ID, and can be reached atoliphant@ pharmacy.isu.edu. In compliance with national ethical guidelines, the author reports no relationships with business or industry that would pose a conﬂict of interest.

http://dx.doi.org/10.1016/j.nurpra.2014.10.018 The Journal for Nurse Practitioners - JNP Volume 11, Issue 1, January 2015 94 R epro duce d w ith p erm is sio n o f th e c o pyrig ht o w ner. F urth er r e pro ductio n p ro hib ite d w ith out p erm is sio n.