Predisposing factors and conditions for TB:

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

• Fever
• Tachycardia
• Hypoxia
• Cachexia
• Abnormal breath sounds
• Cervical lymphadenopathy

• 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 stand ard for diagnosis of TB
  • Average time for positive culture is 3-6 wk
  • DNA polymerase chain reaction (PCR) testing is more rapid
• Lumbar puncture with CSF analysis:
  • For suspected TB meningitis
  • Elevated WBCs with lymphocyte predominance
  • Elevated protein
  • Low to normal glucose

• 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

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)
  • Health care workers
  • Prison inmates
  • Institutionalized (nursing home, homeless shelters)
• >15-mm induration:
  • Low-risk individuals

Serum testing:

• Interferon-gamma release assays:
  • T-SPOT test or QuantiFERON-TB Gold test
  • Can be used to diagnose infection with TB but cannot differentiate between active disease and latent TB
  • Both measure T-cell response (IFN-Y) against specific Mtb antigens in blood
  • Greater specificity for TB than TST in those who received BCG vaccine
  • Better for those who may not return for a second appointment
  • Results can be positive, negative, or indeterminate
  • TST is the preferred test for children <5 yr old
• TB-LAMP assay:
  • Newly developed TB test recommended by the WHO
  • Manual assay that can be done in <1 hr
  • Can be used to replace sputum smear microscopy to diagnose TB only in adult patients with signs and symptoms concerning for TB
  • Can also be used as a secondary test in those who require further testing after a negative sputum smear
• NanoDisk:
  • Developed in 2017, this assay is able to rapidly diagnose active TB using serum
  • It is a quantitative serum-based assay that can detect specific Mtb-peptide fragments with greater sensitivity and specificity in both healthy and immunocompromised populations
  • Not yet commercially available

Drug Susceptibility Testing

• For isoniazid and rifampin should be done in the following patient populations:
  • All HIV patients
  • Those born outside the U.S. or who have spent >1 yr in a country with moderate TB prevalence
  • Those who have had contact with patients with MDR-TB
  • Those previously treated for TB

• Isoniazid: 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 t.i.d:
  • Not recommended <13 yr old, requires visual testing
• Rifapentin: 10 mg/kg, max 900 mg (peds: Not recommended <13 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

(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 q.i.d
• Levaquin: 750 mg (peds: Contraindicated) PO/IV per day

MDR-TB Treatment

• Bedaquiline: 400 mg per day for 2 wk, followed by 200 mg three times per week for 22 wk
  • FDA approved for treatment of MDR-TB in adults
  • First drug that works directly against M. tuberculosis to be approved since 1971
  • Should be used as part of a combination therapy against MDR-TB

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

• 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 mand atory

Referral to Department of Public Health for DOT