Table 4.

Hematologic and Neurologic Events During Treatment With Bedaquiline, Pretomanid, and Linezolid (n = 68)

Event and Patient Descriptions	Linezolid Trough Concentration
Both hematologic and neurologic events requiring linezolid change or discontinuation (n = 1)
69 y female with diabetes, breast cancer (treatment unknown), baseline hemoglobin 10.6 g/dL, and peripheral neuropathy (in fingers and toes); reported blurry vision and received transfusion after 13 d of linezolid 600 mg/d; high serum trough concentration; linezolid changed to 600 mg TIW; no further transfusions or symptoms and full BPaL regimen completed	11.6 µg/mL
Only hematologic events requiring linezolid change or discontinuation (n = 3)
83 y female, with diabetes, untreated hypothyroidism, and baseline hemoglobin 8.0 g/dL; required transfusions before and 10 d after starting linezolid at 600 mg/d; platelet counts “decreasing”; high serum trough concentration; linezolid changed from 600 mg/d to 600 mg TIW; no further transfusions or symptoms and full BPaL regimen completed	9.96 µg/mL
70 y male with baseline gout; admitted with transaminitis, pancreatitis, and anemia on rifampin, isoniazid, pyrazinamide, and ethambutol; after improvement, treatment was changed to BPaL (linezolid, 600 mg/d); in 5th week of BPaL, readmission with recurrent transaminitis, pancreatitis, and anemia requiring 1-unit transfusion of RBCs; steroids given for possible autoimmune etiology; with high trough concentration, linezolid changed to 600 mg TIW; around wk 23, linezolid was discontinued owing to hemoglobin level of 6.9 g/dL; bedaquiline and pretomanid treatment completed	2.9 µg/mL
63 y male with alcoholic cirrhosis, oxygen-dependent lung disease, and baseline anemia with hemoglobin level 8 g/dL, required transfusion before starting linezolid 600 mg/d and again 1 mo after starting; dosage changed to linezolid 600 mg TIW through completion of BPaL regimen	Not done
Only hematologic events not requiring linezolid change or discontinuation (n = 2)
76 y male; linezolid changed empirically from 600 mg/d to 600 mg TIW after 12 d, owing to baseline untreated diabetes and renal disease; low linezolid trough at 48 h; later in therapy, hemoglobin decreased from baseline of 15.4 to 12.3 g/dL and platelet count decreased from 173 109/L to 97 × 109/L, then stabilized; BPaL regimen completed without further linezolid changes	0.39 µg/mL
58 y male with diabetes and chronic hepatitis B; linezolid 900 mg/d started 5 mo before bedaquiline and pretomanid; hemoglobin level of 14.2 g/dL 6 mo after linezolid initiation; linezolid trough was trace; 2 mo later, provider documented “anemia”; linezolid was continued at 900 mg/d, and 26 wk of BPaL treatment was completed	Trace
Only neurologic symptoms requiring linezolid change or discontinuation (n = 3)
76 y male with diabetes, stage 3 chronic kidney disease, and baseline peripheral neuropathy; reported blurry vision after starting linezolid 600 mg/d, but vision examination and Isahara test results were unchanged; vision resolved with change to 600 mg TIW; full BPaL regimen completed	9.3 µg/mL
81 y female with diabetes, hypothyroidism, and vitamin B12 deficiency; started linezolid 600 mg/d; discontinued linezolid at 12 wk for worsened neuropathy despite 1-wk trial of 600 mg TIW; completed bedaquiline and pretomanid treatment	1.13 µg/mL
50 y female with smoking-related chronic lung disease, hypothyroidism, and opioid use disorder; developed persistent hand numbness and discontinued linezolid 600 mg/d at 24 wk without trial of 600 mg TIW; completed bedaquiline and pretomanid treatment	0.3 µg/mL
Neurologic symptoms not requiring change or discontinuation of linezolid (n = 5)
18 y female reported new numbness in toes; linezolid continued at 600 mg/d; symptoms resolved after completion of BPaL regimen	3.3 µg/mL
50 y female with baseline anxiety; reported transient tingling in face and scalp and intermittent numbness/tingling in eyes and fingers; symptoms resolved; linezolid continued at 600 mg/d until completion of BPaL treatment	2.4 µg/mL
25 y male; no symptoms on 600 mg/d but reported numbness and tingling in 2 toes approximately 10 wk after linezolid was increased to 900 mg/d; symptoms persisted throughout treatment but resolved after BPaL completion	1.5 and 2.03 µg/mLa
37 y male with HIV; linezolid increased from 600 to 1200 mg TIW based on TDM, with linezolid trough of 0.1 µg/mL at 48 h; reported arm numbness and weakness that resolved by the end of BPaL treatment	0.1 µg/mL
56 y female with vitamin B12 deficiency; experienced 2 d of tingling in fingertips when gardening, which never recurred; completed BPaL treatment with linezolid 600 mg/d	1.3 µg/mL

Abbreviations: BPaL, bedaquiline, pretomanid, and linezolid; DOT, directly observed therapy; HIV, human immunodeficiency virus; RBCs, red blood cells; TDM, therapeutic drug monitoring; TIW, thrice weekly (Monday, Wednesday, and Friday).