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PRACTICE RECOMMENDATIONS
› Obtain a problem-focused history and physical, as well as chest radiography, to rule out active pulmonary tuberculosis (TB) before initiating treatment for latent tuberculosis infection (LTBI). B
› Prescribe isoniazid 5 mg/kg/d (10 mg/kg/d in children) up to a maximum dose of 300 mg/d for 9 months for most patients with LTBI. B
› Ensure that directly observed therapy is used for all patients with active TB, as well as for select high-risk cases of LTBI. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
CASE › Mitchell J, age 62, comes to see you because he’s had a cough with increasing dyspnea for a month. Mr. J has never smoked but has type 2 diabetes mellitus. He also tells you that over the past month, he’s had occasional night sweats and has lost 8 pounds, although he’s not changed his diet. During the past week, he’s noticed blood-tinged sputum. Physical examination reveals a thin, chronically ill appearing man with an oral temperature of 100.6°F and mild tachypnea. You order a complete blood count, chest x-ray, and metabolic profile, administer a tuberculin skin test (TST), and initiate levofloxacin 500 mg/d for a presumed bacterial pneumonia. His lab work reveals mild leukocytosis and hyperglycemia, and the chest x-ray shows a left upper lobe infiltrate. The TST reaction—4 mm 50 hours after placement—was negative.
Mr. J returns a week later and says he feels worse. Your examination reveals worsened tachypnea, with tachycardia and crackles over the left upper lung fields.
How would you proceed with his care?
More people die of tuberculosis (TB) each year than any other infectious disease except human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. In 2013, an estimated 9 million people worldwide developed active TB and 1.5 million died of the disease.1 Many of these deaths could have been prevented if patients had received a diagnosis and treatment during the latent phase (when the patient was infected, but had no active disease), or as soon as the patient developed active disease. In this article we describe treatment for both latent and active TB.
Before treating latent TB infection, first rule out active TB
Patients with latent tuberculosis infection (LTBI) have a 5% to 10% lifetime risk of developing active TB disease.2 Treatment of LTBI can reduce this risk to 1% to 2%.3
Although not the focus of this article, diagnosis of LTBI is made by using either a TST, in which the patient receives an intradermal injection of purified protein derivative and the size of the skin induration is measured 48 to 72 hours after administration, or an interferon-gamma release assay (IGRA), which requires a blood draw. After receiving a positive test result for LTBI, the next step is to rule out active TB.4 This is necessary because the primary treatment regimen for LTBI involves only one drug, whereas treating active TB with one drug is strongly associated with treatment failure and future resistance to that drug.5
To rule out active TB, perform a brief, problem-focused history and physical, and obtain a chest x-ray.4 Pertinent findings that suggest active disease include:
- any history of recent weight loss, unexplained fever, night sweats, cough or hemoptysis
- fever or any unexpected lung findings on physical exam
- any parenchymal infiltrates on chest x-ray. (Granulomas and scarring may be signs of previously healed TB infection, but do not indicate active TB.)
Any of these findings should prompt a further investigation to either confirm or definitively rule out active TB disease. In the absence of these findings, the physician may proceed with treatment for LTBI.
Latent TB infection treatment: Isoniazid alone, or another regimen?
The current preferred regimen for most patients with LTBI is 9 months of isoniazid (INH) 5 mg/kg/d (10 mg/kg/d in children) up to a maximum of 300 mg/d. This regimen has been recommended by the Centers for Disease Control and Prevention (CDC), the American Thoracic Society, and the Infectious Diseases Society of America.3 However, there are 3 other CDC-recommended LTBI treatment regimens that include INH, INH plus rifapentine (RPT), or rifampin (RIF) for 6, 3, or 4 months, respectively (TABLE 1).6 These other regimens may be considered under certain circumstances. For example, INH and rifapentine might be used to treat an otherwise healthy patient who has had recent exposure to an individual with active, contagious TB.
