Linezolid-Associated Neuropathy in Patients with MDR/XDR Tuberculosis in Shenzhen, China

Figures & data

Table 1 Participant demographic and clinical characteristics

Age (mean ± SD), years	37.6±13.93
Sex
Male	47 (64%)
Female	26 (36%)
History of treated tuberculosis	7 (10%)
Comorbidities
HBV coinfection	6 (8%)
Diabetes mellitus	5 (7%)
End-stage renal disease (on dialysis)	1 (1%)
Liver cirrhosis	1 (1%)
Kidney transplantation	2 (3%)
BMI on presentation, mean ± SD, kg/m^2	20.8±1.4
Albumin level on presentation, mean ± SD, g/L	40.89±4.103
eGFR on presentation, mean ± SD, mL/min	101.41±28.24
Drug resistance
RR-TB	10 (14%)
MDR-TB	56 (77%)
Pre-XDR	5 (7%)
XDR-TB	2 (3%)
Type of tuberculosis
Pulmonary	66 (90%)
Extrapulmonary TB	1 (1%)
Pulmonary and extrapulmonary	6 (8%)
Reported neuropathy	29 (40%)

Abbreviations: HBV, hepatitis B virus; BMI, body-mass index; eGFR, estimated glomerular filtration rate; RR-TB, rifampicin-resistant tuberculosis; MDR-TB, multidrug-resistant tuberculosis; pre-XDR, pre–extensively drug-resistant tuberculosis; XDR-TB, extensively drug-resistant tuberculosis.

Table 2 Regimen composition with duration >1 month

Drug*	n (%)
Linezolid	73 (100%)
Bedaquiline	10 (14%)
Isoniazid	3 (4%)
Ethambutol	6 (8%)
Ethionamide	8 (11%)
Levofloxacin	33 (45%)
Moxiflaxacin	52 (71%)
Cycloserine	65 (89%)
Amikacin	5 (7%)
Pyrazinamide	52 (71%)
Clofazimine	58 (79%)

Notes: *Regimen composition was tailored for every participant based on results of drug-susceptibility testing, guidelines from the WHO and Antituberculosis Committee of China, and affordability of drugs in reference to patients’ financial well-being.

Table 3 Univariate analysis of determinants of neuropathic development

	Neuropathic	Not neuropathic	P
	n=29	n=44
Age, mean ± SD, years	37.54±13.89	37.7±14.26	0.961
Diabetes mellitus	0	5	0.068
End-stage renal disease (on dialysis)	1	0	0.403
BMI, mean ± SD, kg/m^2	20.6±2.2	21±1.5	0.124
Albumin level at presentation, mean ± SD, g/mL	42.28±3.96	40.02±3.99	0.017
eGFR at presentation, mean ± SD, mL/min	93.44±28.9	105.60±27.33	0.111
Trough linezolid concentration >2 mg/L, n (%)	17 (59)	13 (30)	0.013

Figure 1 Serum trough concentration (C_min) in patients on daily linezolid dosages of 300 mg and 600 mg.

Table 4 Clinical characteristics of linezolid-associated neuropathy

	Peripheral neuropathy, n=20	Optic neuropathy, n=7	Both, n=2	P
	n (%)*	n (%)	n (%)
Linezolid trough concentration				0.120
>2 mg/L	14 (70)	3 (43)	0
≤2 mg/L	6 (30)	4 (57)	2 (100)
Time to onset from treatment initiation				0.735
≤2 months	5 (25)	3 (43)	0
>2 to ≤6 months	13 (65)	4 (57)	1 (50)
>6 months	2 (10)	0	1 (50)
Therapy modification				0.001
None	6 (30)	3 (43)	0
Dose lowered to 300 mg/day	10 (50)	4 (57)	2 (100)
Discontinuation of linezolid	4 (20)	0	0
Months from linezolid withdrawal to recovery (median)	6	4	4	0.643