Tuberculosis, Emergency Medicine

Basics

Description

Tuberculosis (TB) is an infectious disease with protean manifestations, causing significant global morbidity and mortality.

Mechanism

Infectious droplet nuclei are inhaled through the respiratory tract.
Bacteria are dispersed through coughing, sneezing, speaking, singing.
Primary TB/latent TB infection (LTBI):
- Initial infection occurs when organisms enter the alveoli, become engulfed by macrophages, and spread via regional lymph nodes to the bloodstream.
- Patients are usually asymptomatic.
- May be progressive/fatal in immunocompromised hosts.
- Positive reaction to purified protein derivative (PPD) indicates past exposure or infection.
- Negative PPD does not rule out active TB.
- May progress to active TB (5 " “10%).
Reactivation TB:
- LTBI becomes active TB.
- Systemic (15%) and pulmonary (85%) symptoms.
TB affects about one-third of the worlds population (90 million new cases in the past decade worldwide, with about 30 million deaths).
Centers for Disease Control and Prevention (CDC) statistics from 2011 show TB in US at an all-time low.
TB rates in US have continued to decline since 1993.
Increase in US foreign-born cases
Still an estimated 10 " “15 million people are infected in US alone.

Etiology

Infection with Mycobacterium tuberculosis, a slow-growing, aerobic, acid-fast bacillus resulting in disease.
Humans are the only known reservoir.
Recent TB epidemics:
- HIV-infected patients
- Multidrug-resistant TB (MDR-TB)
- Extensively drug-resistant TB (XDR-TB):
  - High mortality, few effective drugs

Diagnosis

Signs and Symptoms

Depending upon site of infection; all human tissues have potential for infection.
Pulmonary TB:
- Cough
- Fever, night sweats
- Malaise, weight loss
- Hemoptysis
- Pleuritic chest pain
- Shortness of breath
Extrapulmonary TB:
- CNS infections:
  - Meningismus
  - Cranial nerve defects, diplopia
  - Headache, fever, malaise
  - Confusion
  - Acute ischemic stroke
- Pericarditis:
  - Pleuritic chest pain increased with recumbency
- Renal infection:
  - Fever
  - Flank pain
- Spinal TB (Potts disease):
  - Back pain/stiffness, point tenderness
  - Fever
  - Decreased range of motion
- Cervical lymphadenitis (scrofula):
  - Unilateral, painless
  - May form draining sinus tracts
- Miliary TB:
  - Multiorgan system involvement
  - Diffuse adenopathy
  - Hepatomegaly
  - Splenomegaly
  - Weight loss, fever

History
Predisposing factors and conditions for TB: ‚

HIV infection and other immunocompromised states (organ transplant, renal failure, diabetes)
Drug and alcohol abuse
Poverty, homelessness (living in shelters)
Institutionalization (nursing homes, prisons)
Immigration from an endemic area
Positive PPD test/previous infection

Physical Exam

Fever
Tachycardia
Hypoxia
Cachexia
Abnormal breath sounds
Cervical lymphadenopathy

Essential Workup

Diagnosis difficult due to the variety of clinical presentations.
Chest radiography:
- Most valuable test for active pulmonary TB
Skin testing: PPD

Diagnosis Tests & Interpretation

Lab

CBC
Electrolytes, BUN, creatinine, glucose, LFTs
Hyponatremia (due to syndrome of inappropriate antidiuretic hormone)
ABGs for oxygenation/ventilation assessment
Sputum staining for acid-fast bacilli (Ziehl " “Neelsen stain):
- Provides a quick presumptive diagnosis
Sputum, CSF, blood, urine, or peritoneal fluid culture:
- Gold standard for diagnosis of TB
- Average time for positive culture is 3 " “6 wk.
- DNA polymerase chain reaction (PCR) testing more rapid
Lumbar puncture with CSF analysis:
- For suspected TB meningitis
- Elevated WBCs with lymphocyte predominance
- Elevated protein
- Low to normal glucose

Imaging

Chest radiograph:
- May be normal
- In primary disease, parenchymal infiltrates with unilateral hilar adenopathy are the classic findings.
- Reactivation TB typically appears as cavitary lesions with or without calcification, usually in upper lung segments.
- Miliary TB shows bilateral disseminated 2-mm nodules throughout lungs.
- Chest radiograph may be nondefinitive in AIDS/immunocompromised patients.
- Unilateral pleural effusion in both primary and reactivation TB
- Tracheal deviation with scarring or atelectasis
- Ghon focus " ”calcified scar/healed primary focus of infection
- Ghon complex " ”primary infiltrate with associated unilateral hilar adenopathy
Spine radiographs for Potts disease:
- May be normal
- Anterior wedging of 2 involved vertebral bodies and destruction of disk
CT chest:
- Better defines extent of disease

Diagnostic Procedures/Surgery
Skin testing: ‚

Inject 0.1 mL of PPD intradermally in the forearm.
Positive test indicates prior or current infection with M. tuberculosis.
Test results are read between 48 and 72 hr after administration.
Interpretation of positive: >5-mm induration:
- Close contacts with TB patients
- Positive chest radiographs for TB
- HIV-positive
- Organ transplant or other immunosuppression
>10-mm induration:
- IV drug users
- Immigrants from high-prevalence countries (within 5 yr)
- Underlying disease (diabetes, renal failure, malignancies)
- Healthcare workers
- Prison inmates
- Institutionalized (nursing home, homeless shelters)
>15-mm induration:
- Low-risk individuals

Differential Diagnosis

Bacterial pneumonia
Bronchiectasis
Coccidiomycosis
Histoplasmosis
Lung abscess
Lung carcinoma
Lymphoma
Pneumocystis carinii pneumonia
Pulmonary embolism
Sarcoidosis

Treatment

Pre-Hospital

Place patient in respiratory isolation (negative flow).
Place a mask on the patient to prevent respiratory spread of the disease.
Initiate treatment with an IV, oxygen, and pulse oximetry.
Endotracheal intubation may be required in patients with severe hemoptysis or respiratory compromise.
Providers should wear submicron particulate filter masks (N-95 designation).
Inform close contacts.

Initial Stabilization/Therapy

ABCs:
- Control airway as needed.
- Administer oxygen as needed.
- Place on patient cardiac monitor and pulse oximetry.
- Establish IV access with 0.9% normal saline
Isolate patients in negative pressure rooms with at least 6 air exchanges per hour.
Protection for healthcare workers (N-95 masks)

Ed Treatment/Procedures

Isolation and strict respiratory precautions
Treatment is augmented due to increasing multidrug resistance.
Any regimen must contain at least 2 drugs to which the TB bacillus is susceptible.
CDC currently recommends initial therapy that includes 4 1st-line drugs.
LTBI with normal chest x-ray given isoniazid (INH) for 9 mo or weekly combination of INH and rifapentine (RPT) for 12 wk.
Consult infectious disease specialists when treating HIV patients on antiretroviral therapies.
Add dexamethasone for TB meningitis.
Surgical drainage for TB empyema may be necessary; consult thoracic surgeon.
Directly observed therapy (DOT) may be necessary to ensure compliance in certain populations.
Intermittent (biweekly) regimen may demonstrate higher patient compliance.

Medication

First Line

INH: 5 mg/kg, max. 300 mg (peds: 10 " “15 mg/kg, max. 300 mg) PO/IM per day:
- Refractory seizures in overdose, treat with pyridoxine 5 g IV over 5 min or PO
- Caution with alcohol coingestion, hepatitis
Rifampin (RIF): 10 mg/kg, max. 600 mg (peds: 10 " “20 mg/kg, max. 600 mg) PO/IV per day
Pyrazinamide (PZA): 20 " “25 mg/kg/d max. 2 g (peds: 15 " “30 mg/kg/d) or:
- <55 kg: 1 g PO per day
- 56 " “75 kg: 1.5 g PO per day
- >75 kg: 2 g PO per day
- Not recommended in pregnancy
Ethambutol (ETB): 15 " “20 mg/kg, max. 1,600 mg (peds: 15 " “30 mg/kg, max. 1 g) PO per day or up to TID
- Not recommended <13 yr old, requires visual testing
RPT: 10 mg/kg, max. 900 mg (peds: Not recommended <12 yr old) PO once per week or 300 mg PO weekly for 10 " “14 kg, 450 mg PO weekly for 14.1 " “25 kg, 600 mg PO weekly for 25.1 " “32 kg, 750 mg PO weekly for 32.1 " “49.9 kg, 900 mg PO weekly for >50 kg
Rifabutin: 5 mg/kg, max. 300 mg (peds: Unknown) PO per day

Second Line
(Less Effective, More Toxic)

Streptomycin: 15 mg/kg/d, max. 1 g (peds: 20 " “40 mg/kg/d) IM/IV per day:
- Teratogenic: Contraindicated in pregnancy
Ethionamide: 0.5 " “1 g (peds: 10 " “20 mg/kg/d) PO div. QID
Levaquin: 750 mg (peds: Contraindicated) PO/IV per day

Follow-Up

Disposition

Admission Criteria

Respiratory compromise
Suspicion of diagnosis
Inability to comply with outpatient therapy
Unavailable outpatient resources (no PCP)
Involuntary admission for noncompliant outpatients occurs:
- Be aware of respective state laws concerning involuntary admission (consult infectious disease specialist).

Discharge Criteria

Without respiratory compromise
Home isolation procedure compliance
Ability and willingness to comply with long-term therapy
Appropriate outpatient follow-up and treatment available
Notification of the public health authorities is mandatory.

Issues for Referral
Referral to Department of Public Health for DOT ‚

Follow-Up Recommendations

Sputum analysis periodically to document clearance
Medication toxicity monitoring:
- INH, RIF, PZA: Monitor liver function tests for hepatitis
- PZA: Check uric acid levels
- ETB: Eye testing for color blindness

Pearls and Pitfalls

Early isolation and respiratory precautions
Careful history to establish risk factors
The chest x-ray and PPD are great diagnostic aids.
Initial 4-drug regimen for active disease
Nonadherent, active TB patients are considered a public health hazard:
- Specific state laws are applicable in numerous areas.

Additional Reading

American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52(RR-11):1 " “77.
American Thoracic Society; Centers for Disease Control and Prevention; Infectious Diseases Society of America. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Controlling tuberculosis in the United States. Am J Respir Crit Care Med. 2005;172:1169 " “1227.
Centers for Disease Control and Prevention (CDC). Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection. MMWR. 2011;60(RR-48):1650 " “1653.
Moran ‚ GJ, Talan ‚ DA.Tuberculosis. In: Wolfson ‚ AB, ed. Harwood-Nuss ' Clinical Practice ofEmergency Medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins: 2010:912 " “917.
Taylor ‚ Z, Nolan ‚ CM, Blumberg ‚ HM. Controlling tuberculosis in the United States. Recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR Recomm Rep. 2005;54(RR-12):1 " “81. http://www.cdc.gov/tb/publications/factsheets/statistics/TBTrends.html. Accessed on February 28, 2013.

Codes

ICD9

010.90 Primary tuberculous infection, unspecified, unspecified
011.90 Unspecified pulmonary tuberculosis, unspecified
795.51 Nonspecific reaction to tuberculin skin test without active tuberculosis
018.90 Miliary tuberculosis, unspecified, unspecified
013.20 Tuberculoma of brain, unspecified
017.90 Tuberculosis of other specified organs, unspecified

ICD10

A15.7 Primary respiratory tuberculosis
A15.9 Respiratory tuberculosis unspecified
R76.11 Nonspecific reaction to skin test w/o active tuberculosis
A19.9 Miliary tuberculosis, unspecified
A17.81 Tuberculoma of brain and spinal cord
A18.84 Tuberculosis of heart
A18.89 Tuberculosis of other sites

SNOMED

56717001 Tuberculosis (disorder)
63309002 Primary tuberculosis (disorder)
441846005 Nonspecific tuberculin test reaction (finding)
47604008 Miliary tuberculosis (disorder)
302131003 Tuberculosis of heart (disorder)
31112008 Tuberculous meningoencephalitis (disorder)

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