Test your knowledge with this USMLE Step 2 Question of the Day. A 37-year-old man with a history of hypertension and frequent travel to tuberculosis-endemic regions presents for a routine visit. He has no symptoms, but his tuberculin skin test and interferon-gamma assay are positive. The patient is initiated on isoniazid to treat latent tuberculosis. Which additional medication should be administered to prevent potential side effects?
A 37-year-old man comes to his outpatient provider for a routine visit. The patient is feeling well and has no symptoms. Past medical history is notable for hypertension. He works as a consultant and frequently travels overseas to meet with clients in China and India. Temperature is 37.0°C (98.6°F), blood pressure is 157/86 mmHg, and pulse is 75/min. Physical examination is unremarkable. A purified protein derivative injection is performed. After two days, a wheal measuring 16 mm in diameter is present at the injection site. An interferon-gamma test is performed and returns positive. The patient is initiated on a medication that inhibits the bacterial synthesis of mycolic acid. Which of the following additional medications should be administered to this patient?
A. Ethambutol
B. Vitamin B1
C. Pyrazinamide
D. Vitamin B6
E. Streptomycin
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 2 CK Question is…
D. Vitamin B6
Before we get to the Main Explanation, let’s see why the answer wasn’t A, B, C, or E. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
Today’s incorrect answers are…
A. Ethambutol
Incorrect: Ethambutol is a medication used to treat active tuberculosis. Ethambutol works by inhibiting arabinogalactan synthesis, as opposed to mycolic acid synthesis. In contrast, this patient has evidence of latent tuberculosis since he remains asymptomatic despite having a positive purified protein derivative (PPD) test and interferon-gamma assay.
B. Vitamin B1
Incorrect: Vitamin B1, also known as thiamine, can be administered to patients with chronic alcohol abuse or other forms of malnutrition to reduce the risk of Wernicke encephalopathy. However, this patient does not have a history of malnutrition. Furthermore, he was started on isoniazid to treat latent tuberculosis and would more likely require vitamin B6 supplementation.
C. Pyrazinamide
Incorrect: Pyrazinamide is a medication used to treat active tuberculosis. In contrast, this patient has latent tuberculosis since he remains asymptomatic despite having a positive purified protein derivative (PPD) test and interferon-gamma assay.
E. Streptomycin
Incorrect: Streptomycin is an aminoglycoside that can be used with other medications to treat miliary tuberculosis and Mycobacterium tuberculosis meningitis. Streptomycin works by inhibiting the bacterial 30S ribosomal subunit and preventing protein synthesis instead of inhibiting mycolic acid synthesis.
Main Explanation
This patient has traveled to tuberculosis-endemic regions and has a positive tuberculin skin test and interferon-gamma assay but remains asymptomatic. He likely has latent tuberculosis and was appropriately initiated on isoniazid therapy. Patients on isoniazid should also receive vitamin B6 (pyridoxine) supplementation.
Isoniazid can be used alone to treat latent tuberculosis or in combination with other medications to treat active tuberculosis. The medication inhibits mycolic acid synthesis, an essential component of the mycobacterial cell wall. It also inhibits mycobacterial peroxidase, which leads to hydrogen peroxide accumulation within mycobacteria inducing cellular damage.
Isoniazid use may lead to pyridoxine deficiency, manifest with sideroblastic anemia, encephalopathy, ataxia, dizziness, and peripheral neuropathy. Fortunately, these side effects can be prevented with pyridoxine supplementation. As a result, patients taking isoniazid should receive daily pyridoxine.

Major takeaway
Isoniazid is used to treat tuberculosis and can cause vitamin B6 (pyridoxine) deficiency. Patients on isoniazid should receive daily pyridoxine supplementation.
References
O’Connor, C., Brady, M.F. (2020) “Isoniazid”. StatPearls [Internet]. Web Address: https://www.ncbi.nlm.nih.gov/books/NBK557617/.
Snider Jr., D.E. (1980) Pyridoxine supplementation during isoniazid therapy. Tubercle. 61(4), 191-196. Doi: 10.1016/0041-3879(80)90038-0.
Sotgiu, G., Centis, R., D’ambrosio, L., Migliori, G.B. (2015) Tuberculosis treatment and drug regimens. Cold Spring Perspectives in Medicine. 5(5), a017822. Doi: 10.1101/cshperspect.a017822.
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