Critical Care Medicine-Infections and Immunologic Disease>>>>>Antimicrobial Therapy and Resistance
Question 1#

A 37-year-old man from Thailand presents to the emergency room with hypoxemia and a 6-week history of coughing, including occasional small-volume hemoptysis. Chest X-ray demonstrates a right lower lobe cavitary lesion. He is placed in a negative-pressure isolation room in the intensive care unit (ICU) and started on rifampicin, isoniazid, ethambutol, pyrazinamide, and clindamycin. Nine days after starting antibiotics, his transaminases are elevated, with alanine aminotransferase 1237 IU/mL and aspartate aminotransferase 964 IU/mL.

Which of the following medication(s) is MOST likely to have caused his acute hepatic injury?

A. Ethambutol
B. Rifampicin, isoniazid, or pyrazinamide
C. Clindamycin
D. Isoniazid

Correct Answer is B

Comment:

Correct Answer: B

Three of the four first-line drugs used to treat tuberculosis (rifampicin, isoniazid, pyrazinamide) can be hepatotoxic. In patients being treated for tuberculosis, the most important step is to determine all potential causes of hepatitis, and stop all nonessential medications that could be causing drug-induced hepatitis. If tuberculosis medications are the suspected culprit(s), it is recommended that all antituberculosis treatment be stopped. If the patient is critically ill from tuberculosis, a nonhepatotoxic regimen can be substituted, including ethambutol, streptomycin, and a fluoroquinolone.

References:

1. Tweed CD, Wills GH, Crook AM, et al. Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study. BMC Med. 2018;16:46.
2. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63:e147-e195.
3. WHO. Treatment of Tuberculosis: Guidelines. 4th ed. Geneva, Switzerland: World Health Organization; 2010.