ZSFG AM Report 6/13/2017: Unresolving Fever and Work-Up for Active Tuberculosis

Thank you to Tim and Sarah for presenting a case of a patient with sepsis physiology with unresolving fevers, significantly elevate alk phos, despite broad-spectrum antibiotics who was ultimately thought to have military TB.


Top Pearls:

  1. In a patient with abnormal findings on chest X-ray, not responding to antibiotic therapy, reassess and think about wrong bug, wrong drug, or poor source control
  2. The ability of Gene X-pert and all testing for active tuberculosis is dependent upon a good sputum sample.
  3. When there is a high index of suspicion, ordering a 2nd Gene X-pert and a 2nd AFB smear and culture is indicated.


Additional Tips for Testing for Active M. Tuberculosis (and Concern for Miliary TB):

-Remember that PPD and quantiferon-gold have no role in assessing for active TB (these assess for latent tuberculosis)

-If these tests are performed and positive, it can support the diagnosis of tuberulcosis but positive tests cannot distinguish between active and prior infection or the degree of spread. Negative tests DO NOT exclude the diagnosis of tuberculosis.


-Acid-fast smear and culture:

  • -If multiple sites are available for sample (i.e. sputum, pleural fluid, ascites), the more locations, the better as this can support dx of miliary TB
  • -IDSA Guidelines recommend sputum volumes for AFB smear and culture of at least 3mL although 5-10mL is the optimal volume.


-Gene Xpert assay can detect M. tuberculosis within 2 hours with a sensitivity much higher than that of smear microscopy, especially in patients with HIV (increased rate of case detection by 45% compared to smear microscopy).

  • -In a study of 1730 patients, Gene X-pert identified 98.2% of patients who were AFB smear positive and 72% of patients who were  AFB smear negative
  • -In patients who were AFB smear negative, culture positive tuberculosis, the addition of a 2nd Gene X-pert increased the sensitivity by 12.6%


**Note: If diagnosis is miliary TB, sputum samples may be negative as the spread of organism is hematogenous. Diagnosis may require bronchoscopy with biopsy.


-AFB Blood Culture:

  • Should be obtained in patient when hematogenous spread is suspected
  • Note that positive AFB cultures are rarely positive (but may be seen in immunocompromised patients)



  • -If you can biopsy an area that you think has TB, you may see granulomas, organisms on acid fast staining.
  • -Remember that you can also send AFB cultures from these tissues

As a reminder of the ZSFG TB Testing Guidelines:

TB Work-Up Flowsheet


Boerhme et al. (2010). Rapid molecular detection of tuberculosis and rifampin resistance. NEJM 363:1005-1015.

Zulma et al. (2013). Tuberculosis. NEJM 368:745-755.

Lewinsohn (2016). Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clinical Infectious Diseases. 64:e1-33


Evernote Link: https://www.evernote.com/shard/s509/sh/4f565a9c-a512-4704-be44-b769807803aa/f0c99b5766d625868415f52936c679b7


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