1. Prepared by Sanika Satoskar, MD and reviewed by Claire Knezevic, Ph.D.

A young adult patient is admitted for recurrent respiratory illnesses with symptoms of cough, fevers, aches, and night sweats. During this time, patient has also had poor appetite with weight loss, consist with severe malnutrition. On physical exam, patient is noted to be febrile, cachectic, and ill-appearing. Labs are significant for hyponatremia (130 mmol/L), hypokalemia (3.3 mmol/L), hypophosphatemia (1.9 mg/dL), hypochloremia (93 mmol/L), anemia (Hgb: 8.8 g/dL), elevated LDH (477 U/L), and elevated inflammatory markers (CRP: 11.2 mg/dL). Blood cultures are negative. Imaging is consistent with multiple bilateral pulmonary consolidation and bronchiectasis with centrilobular nodules, concerning for cavitary lesions.

 

Upon further investigation, family history is significant for exposure to active tuberculosis (TB) and possible mold exposure. An extensive infectious workup is performed. T-spot is positive and mycobacterial culture smear comes back heavily positive for acid-fast bacilli. Xpert MTB/RIF is positive for TB and does not show evidence of rifampin resistance. 5-drug TB treatment (RIPE and moxifloxacin) is begun and patient is discharged home for outpatient management.

Patient is admitted back 2 months later due to failure of outpatient therapy with worsening symptoms and most notably, undetectable levels of their TB oral medications. After several repeated undetectable drug levels, dose escalation is performed. Acetylation studies and lymphocyte subset panel are performed and results are below.

N-Acetyltransferase 2 gene testing:NAT2 genotype: NAT2*6/*6

NAT2 phenotype: slow acetylator

Lymphocyte Subset Panel (T-Cell, NK-cell, CD19):CD3+: 82.0%

CD4+: 59.5%

Absolute CD4+: 960 /CUMM

CD8+: 20.5%

CD4/CD8 Ratio: 2.90

CD16+56+: 9.3%

CD19+: 8.5%

Which of the following reasons is the most likely cause of their worsening symptoms?