Practice Essentials
Tuberculosis (TB) (see the image below), a multisystemic disease with myriad presentations and manifestations, is the most common cause of infectious disease–related mortality worldwide. Although TB rates are decreasing in the United States, the disease is becoming more common in many parts of the world. In addition, the prevalence of drug-resistant TB is increasing worldwide.
Anteroposterior chest radiograph of a young patient who presented to the emergency department (ED) with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine (remotemedicine.org).
See 11 Travel Diseases to Consider Before and After the Trip, a Critical Images slideshow, to help identify and manage infectious travel diseases.
Signs and symptoms
Classic clinical features associated with active pulmonary TB are as follows (elderly individuals with TB may not display typical signs and symptoms):
Cough
Weight loss/anorexia
Fever
Night sweats
Hemoptysis
Chest pain (can also result from tuberculous
acute pericarditis)
Fatigue
Symptoms of tuberculous meningitis may include the following:
Headache that has been either intermittent or persistent for 2-3 weeks
Subtle mental status changes that may progress to coma over a period of days to weeks
Low-grade or absent fever
Symptoms of skeletal TB may include the following:
Back pain or stiffness
Lower-extremity paralysis, in as many as half of patients with undiagnosed
Pott disease
Tuberculous arthritis, usually involving only 1 joint (most often the hip or knee, followed by the ankle, elbow, wrist, and shoulder)
Symptoms of genitourinary TB may include the following:
Flank pain
Dysuria
Frequent urination
In men, a painful scrotal mass, prostatitis, orchitis, or
epididymitis
In women, symptoms mimicking
pelvic inflammatory disease
Symptoms of gastrointestinal TB are referable to the infected site and may include the following:
Nonhealing ulcers of the mouth or anus
Difficulty swallowing (with esophageal disease)
Abdominal pain mimicking peptic ulcer disease (with gastric or duodenal infection)
Malabsorption (with infection of the small intestine)
Pain, diarrhea, or hematochezia (with infection of the colon)
Physical examination findings associated with TB depend on the organs involved. Patients with pulmonary TB may have the following:
Abnormal breath sounds, especially over the upper lobes or involved areas
Rales or bronchial breath signs, indicating lung consolidation
Signs of extrapulmonary TB differ according to the tissues involved and may include the following:
Confusion
Coma
Neurologic deficit
Lymphadenopathy
Cutaneous lesions
The absence of any significant physical findings does not exclude active TB. Classic symptoms are often absent in high-risk patients, particularly those who are immunocompromised or elderly.
See Clinical Presentation for more detail.
Diagnosis
Screening methods for TB include the following:
Mantoux tuberculin skin test
with purified protein derivative (PPD) for active or latent infection (primary method)
In vitro blood test based on interferon gamma release assay (IGRA) with antigens specific for
Mycobacterium tuberculosis for latent infection
Obtain the following laboratory tests for patients with suspected TB:
Acid-fast bacilli (AFB) smear and culture using sputum obtained from the patient: Absence of a positive smear result does not exclude active TB infection; AFB culture is the most specific test for TB
HIV serology in all patients with TB and unknown HIV status: Individuals infected with HIV are at increased risk for TB
Other diagnostic testing may warrant consideration, including the following:
Specific enzyme-linked immunospot (ELISpot)
Nucleic acid amplification tests
Blood culture
Positive cultures should be followed by drug susceptibility testing; symptoms and radiographic findings do not differentiate multidrug-resistant TB (MDR-TB) from fully susceptible TB. Such testing may include the following:
Direct DNA sequencing analysis
Automated molecular testing
Microscopic-observation drug susceptibility (MODS) and thin-layer agar (TLA) assays
Additional rapid tests (eg, BACTEC-460, ligase chain reaction, luciferase reporter assays, FASTPlaque TB-RIF)
Obtain a chest radiograph to evaluate for possible associated pulmonary findings. The following patterns may be seen:
Cavity formation: Indicates advanced infection; associated with a high bacterial load
Noncalcified round infiltrates: May be confused with lung carcinoma
Homogeneously calcified nodules (usually 5-20 mm): Tuberculomas, representing old infection
Primary TB: Typically, pneumonialike picture of infiltrative process in middle or lower lung regions
Reactivation TB: Pulmonary lesions in posterior segment of right upper lobe, apicoposterior segment of left upper lobe, and apical segments of lower lobes
TB associated with HIV disease: Frequently atypical lesions or normal chest radiographic findings
Healed and latent TB: Dense pulmonary nodules in hilar or upper lobes; smaller nodules in upper lobes
Miliary TB: Numerous small, nodular lesions that resemble millet seeds
Pleural TB: Empyema may be present, with associated pleural effusions
Workup considerations for extrapulmonary TB include the following:
Biopsy of bone marrow, liver, or blood cultures
If tuberculous meningitis or tuberculoma is suspected, perform lumbar puncture
If vertebral (
Pott disease) or brain involvement is suspected, CT or MRI is necessary
If genitourinary complaints are reported, urinalysis and urine cultures can be obtained
See Workup for more detail.
Management
Physical measures (if possible or practical) include the following:
Isolate patients with possible TB in a private room with negative pressure
Have medical staff wear high-efficiency disposable masks sufficient to filter the bacillus
Continue isolation until sputum smears are negative for 3 consecutive determinations (usually after approximately 2-4 weeks of treatment)
Initial empiric pharmacologic therapy consists of the following 4-drug regimens:
Isoniazid
Rifampin
Pyrazinamide
Either ethambutol or streptomycin
Special considerations for drug therapy in pregnant women include the following:
In the United States, pyrazinamide is reserved for women with suspected MDR-TB
Streptomycin should not be used
Preventive treatment is recommended during pregnancy
Pregnant women are at increased risk for isoniazid-induced hepatotoxicity
Breastfeeding can be continued during preventive therapy
Special considerations for drug therapy in children include the following:
Most children with TB can be treated with isoniazid and rifampin for 6 months, along with pyrazinamide for the first 2 months if the culture from the source case is fully susceptible.
For postnatal TB, the treatment duration may be increased to 9 or 12 months
Ethambutol is often avoided in young children
Special considerations for drug therapy in HIV-infected patients include the following:
Dose adjustments may be necessary
Rifampin must be avoided in patients receiving protease inhibitors; rifabutin may be substituted
Considerations in patients receiving antiretroviral therapy include the following:
Patients with HIV and TB may develop a paradoxical response when starting antiretroviral therapy
Starting antiretroviral therapy early (eg, < 4 weeks after the start of TB treatment) may reduce progression to AIDS and death
In patients with higher CD4+ T-cell counts, it may be reasonable to defer antiretroviral therapy until the continuation phase of TB treatment
Multidrug-resistant TB
Multidrug-resistant TB (MDR-TB) refers to isolates that are resistant to both isoniazid and rifampin (and possibly other drugs). When MDR-TB is suspected, start treatment empirically before culture results become available; obtain molecular drug susceptibility testing, if possible. Modify the initial regimen, as necessary, based on susceptibility results. Never add a single new drug to a failing regimen. Administer at least 5 drugs for the intensive phase of treatment and at least 4 drugs for the continuation phase (listed in order of preference), as follows:
A fluoroquinolone: levofloxacin or moxifloxacin preferred
Bedaquiline
Linezolid
Clofazimine (available only through Investigational New Drug application through FDA)
Cycloserine
An aminoglycoside: streptomycin or amikacin preferred
Ethambutol
Pyrazinamide
Delamanid
Ethionamide
Para-aminosalicylic acid
Surgical resection is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Procedures include the following:
Segmentectomy (rarely used)
Lobectomy
Pneumonectomy
Pleurectomy for thick pleural peel (rarely indicated)
Latent TB
Recommended regimens for isoniazid and rifampin for latent TB have been published by the US Centers for Disease Control and Prevention (CDC)
: An alternative regimen for latent TB is isoniazid plus rifapentine as self-administered or directly observed therapy (DOT) once-weekly for 12 weeks
; it is not recommended for children under 2 years, pregnant women or women planning to become pregnant, or patients with TB infection presumed to result from exposure to a person with TB that is resistant to 1 of the 2 drugs.
See Treatment and Medication for more detail.