Table 1

Clinical profiles, treatment regimens, and major side effectsa

Patient identifier: sex/age (yr)b/initial body wt (kg)/resistance patternLZD dosage in mg in chronological order (duration in mo) plus other drugscInitial sputum smearInitial findings on chest X-rayOnset of sputum culture conversiond (no. of mo)Total treatment duration [follow-upe] (no. of mo)Major side effect(s)f
A: male/61/61.5/XDR800 OD (3.75) plus INH*/Pto*/Cy*/Cm/Z/Lv; 1,200 TIW (2.5) plus INH*/Pto*/Cy*/Cm/Z/Lv; 1,200 TIW (5.25) plus INH*/Pto*/Cy*/Z/Lv; 1,200 TIW (6.5) plus INH*/Pto*/Cy*/LvPosCavitary, >RUL, <right lung2.518.0 [24.0]Hb < 10 g/dl during daily LZD dosing
B: male/22/69.5/FQ-resistant MDR800 OD (3) plus INH*/E*/Km*/Cy*/PAS*/Lv; 1,200 TIW (3) plus INH*/E*/Km*/Cy*/PAS*/Lv; 1,200 TIW (1) plus INH*/E*/Km*/Cy*/Lv; 1,200 TIW (11) plus INH*/E*/Cy*/LvNegNoncavitary, <RUL0.518.0 [24.5]No
C: male/43/52/XDR800 OD (4) plus INH*/Cy*/PAS/Pto/Lv; 1,200 TIW (12) plus INH*/Cy*/PAS/Pto/Lv; 600 TIW (4) plus INH*/Cy*/PAS/Pto/LvPosCavitary, >right lung1.520.0 [19.5]Mild PN
D: male/49/58.5/XDR800 OD (1.75) plus INH*/Cy*/Lv; 800 OD (2.5) plus INH*/Cy*/PAS/Lv; 1,200 TIW (13.75) plus INH*/Cy*/LvPosCavitary, <RUL3.018.0 [18.5]No
E: female/41/54.6/XDR800 OD (3.75) plus INH*/Cy/Z/Lv; 1,200 TIW (4.75) plus INH*/Cy/Z/Lv; 1,200 TIW (0.5) plus INH*/Z/Lv; 1,200 TIW (2.75) plus INH*/Lv; 600 TIW (4.25) plus INH*/LvPosCavitary, <RUL2.516.0 [21.5]Hb < 10 g/dl during daily LZD dosing; mild PN
F: male/31/54.5/XDR600 BD (0.5) plus PAS*/Cy/Am/Mox; 800 OD (3.0) plus PAS*/Cy/Pto/Am/Lv; 800 OD (0.75) plus INH*/PAS*/Cy/Pto/Lv; 1,200 OD (1)g plus INH*/PAS*/Cy/Pto/Lv; 1,200 TIW (3.5) plus INH*/PAS*/Lv; 600 TIW (6.0) plus INH*/PAS*/Lv; 600 TIW (3.25) plus INH*/LvPosCavitary, >right lung4.018.0 [12.0]Hb < 10 g/dl during daily LZD dosing; mild PN
G: male/53/54/XDR800 OD (0.75) plus PAS*/Cfz/Cm/Cy/Lv; 800 OD (1.5) plus Pto*/PAS*/Cfz/Cm/Lv; 800 OD (0.75) plus Pto*/PAS*/Cfz/Lv; 1,200 TIW (2.0) plus Pto*/PAS*/Lv; 1,200 TIW (7.5) plus INH*/PAS*/Lv; 1,200 TIW (5.5) plus INH*/LvNegCavitary, <RUL1.018.0 [9.0]No
H: female/49/39.7/XDR800 OD (2.5) plus Pto*/PAS*/Cy/Lv; 1,200 TIW (8.5) plus INH*/Pto*/PAS*/Lv; 1,200 TIW (2.25) plus INH*/Pto*/Lv; 1,200 TIW (3.0) plus INH*/LvPosCavitary, <RUL5.016.25 [10.5]No
I: female/32/53/FQ-resistant MDR800 OD (1.25) plus Km*/Pto*/Cy*/PAS*/Lv; 1,200 TIW (0.75) plus Km*/Pto*/Cy*/PAS*/Lv; 1,200 TIW (2.25) plus Km*/Pto*/Lv; 1,200 TIW (2.5) plus Km*/PAS*/Lv; 1,200 TIW (5.25) plus PAS*/LvNegNoncavitary, <RUL<0.5 (within 3 days)12.0 [6.0]No
Jh: male/31/51.5/FQ-resistant MDR600 BD (0.5) plus Z*/Am*/Cy*/Mox; 800 OD (2.75) plus Z*/Am*/Pto*/Cy*/Lv; 1,200 TIW (6.0) plus Z*/Pto*/Cy*/Lv; Nil (8.0) plus INH*/Z*/Pto*/Cy*/Lv; Nil (6.0) plus INH*/Z*NegNoncavitary, <RUL2.023.25 [16.0]Hb < 10 g/dl throughout daily LZD dosing; severe PN
  • a Seven patients (A to G) had previous treatment failure of XDR-TB or relapse of FQ-resistant MDR-TB/XDR-TB. Linezolid was previously given for 2 to 4 months in four patients (A, B, C, E) and stopped because of side effects. Abbreviations: Am, amikacin; BD, twice daily; Cfz, clofazimine; Cm, capreomycin; Cy, cycloserine; DST, drug susceptibility testing; E, ethambutol; FQ, fluoroquinolone; Hb, hemoglobin; INH, isoniazid; Km, kanamycin; Lv, levofloxacin; LZD, linezolid; MDR, multidrug resistant; Mox, moxifloxacin; Neg, negative; OD, once daily; PAS, para-aminosalicylic acid; Pos, positive; Pto, prothionamide; PN, peripheral neuropathy; RUL, right upper lobe; TIW, thrice weekly; XDR, extensively drug resistant; Z, pyrazinamide.

  • b Age when linezolid-containing regimen was started.

  • c An asterisk denotes the presence of in vitro activity according to drug susceptibility testing. Isoniazid is considered as having in vitro activity if its MIC is >0.2 mg/liter and ≤1 mg/liter.

  • d Counted from start of treatment. Sputum culture conversion was defined as having two sets of consecutive negative cultures, from samples collected at least 30 days apart (16).

  • e Counted from treatment completion to the last date of clinical assessment involving sputum and chest radiographic examination.

  • f A dagger denotes partial improvement in peripheral neuropathy.

  • g Instead of giving linezolid at 1,200 mg thrice weekly immediately after linezolid at 800 mg once daily, linezolid at 1,200 mg 5 times per week was given because sputum acid-fast bacillus smear was positive, with subsequent culture found to be negative.

  • h Patient J also had graft-versus-host disease after receiving a bone marrow transplant for leukemia. He also received thalidomide when peripheral neuropathy occurred. Linezolid was stopped in view of good clinical progress and severe peripheral neuropathy.