Drug Non-Adherence And Reasons Among Multidrug-Resistant Tuberculosis Patients In Guizhou, China: A Cross-Sectional Study

Figures & data

Table 1 Drug, Daily Dosage, Price, Classification In China’s National Basic Medical Insurance List And Recommended In The Standardized Treatment Regimen

Group	Description	Drug (Abbrev.)	Daily Dosage (mg) By Patient Weight			Range Of Monthly Cost (CNY)	Included In National Basic Medical Insurance List			Recommended In Standardized Treatment Regimen
			<50 kg	≥50 kg	Maximum		Yes		No^c
							Most preferred^a	Preferred^b
1	First-line oral anti-TB drugs	Pyrazinamide (Z)	1500	1750	2000	58–96	√			√
		Ethambutol (E)	750	1000	1500	21–34	√			√
2	Injectable anti-TB drugs	Amikacin (Am)	400	400–600	800	72–108	√			√
		Capreomycin (Cm)	750	750	750	712		√		√
		Kanamycin (Km)	500	750	1000	1500			√	√
3	Fluoroquinolones (FQs)	Ofloxacin (Ofx)	400	600	800	110–165	√
		Levofloxacin (Lfx)	400	500	600	60–110	√			√
		Moxifloxacin (Mfx)	400	400	400	698		√		√
4	Oral bacteriostatic second-line anti-TB drugs	Prothionamide (Pto)	600	600–800	800	40–53		√		√
		p-aminosalicylic acid (PAS)	8000	10,000	12,000	600–900	√			√
		Cycloserine (Cs)	500	750	1000	1620–1920		√		√
5	Anti-TB drugs with limited data on efficacy and/or long-term safety in the treatment of drug-resistant TB	Amoxicillin/Clavulanate (Amx/Clv)	1125	1,500	1500	1260–1680	√
		Clarithromycin (Clr)	500	750	1000	126–252		√
		Linezolid (Lzd)	300	300–600	600	9600–19,200		√
		Clofazimine (Cfz)	100	100	100	1248		√

Notes: ^aMost preferred: totally reimbursed by insurance ;^13,15 bPreferred: partially reimbursed by insurance system;^13,15 cNo: paid out-of-pocket.

Abbreviations: MDR-TB, multidrug-resistant tuberculosis; CNY, Chinese yuan.

Table 2 Comparison Of Patient Characteristics Among The Three Groups

Characteristic	Total Registered Patients At The Hospital (n=268)	Patients Interviewed At The Hospital (n=202)	Patients Interviewed At Their Home (n=111)
	n (%)	n (%)	n (%)
Gender
Female	83 (31.0)	67 (33.2)	34 (30.6)
Male	185 (69.0)	135 (66.8)	77 (69.4)
Age (Median, IQR)	37 (27, 49)	36 (26, 48)	38 (27, 48)
Ethnic group
Han	199 (74.3)	140 (69.3)	83 (74.8)
Other	69 (25.7)	62 (30.7)	28 (25.2)
Occupation before MDR-TB
Migrant worker	55 (20.5)	52 (25.7)	26 (23.4)
Farmer	103 (38.4)	61 (30.2)	40 (36.0)
Government worker	15 (5.6)	15 (7.4)	5 (4.5)
Company worker	37 (13.8)	37 (18.3)	17 (15.3)
Student	26 (9.7)	26 (12.9)	16 (14.4)
Unemployed	32 (11.9)	11 (5.4)	7 (6.3)
Area of residence
Urban	46 (17.2)	41 (20.3)	19 (17.1)
Rural	222 (82.8)	161 (79.7)	92 (82.9)
Classification of MDR-TB
Primary	24 (9.0)	21 (10.4)	11 (9.9)
Secondary	244 (91.0)	181 (89.6)	100 (90.1)
Duration of treatment (months)
<12	76 (28.4)	60 (29.7)	35 (31.5)
12–24	192 (71.6)	142 (70.3)	76 (68.5)
Marital status
Single	–	78 (38.6)	38 (34.2)
Married	–	124 (61.4)	73 (65.8)
Education level
Primary school or less	–	60 (29.7)	39 (35.1)
Middle school	–	68 (33.7)	30 (27.0)
High school	–	55 (27.2)	35 (31.5)
University	–	19 (9.4)	7 (6.3)
Occupational status after getting MDR-TB
Still working	–	62 (30.7)	31 (27.9)
Lost job or could not work	–	103 (51.0)	57 (51.4)
Student/unemployed	–	37 (18.3)	23 (20.7)
Per capita annual income (Median, IQR)	–	1761 (1172, 3258)	1574 (1003, 3168)
Insurance scheme
UEBMI	–	22 (10.9)	8 (7.2)
URBMI	–	6 (3.0)	4 (3.6)
NRCMS	–	169 (83.7)	99 (89.2)
None		5 (2.5)	0
Monthly drug costs before reimbursement (Mean, SD)	–	240.6, 160.2	245.4, 166.6
Monthly OOP of drug costs (Mean, SD)	–	149.5, 157.3	152.6, 166.2
In debt due to MDR-TB	–	120 (59.4)	66 (59.5)
Received DOT	–	56 (27.7)	30 (27.0)
Baseline co-morbidity	–	40 (19.8)	27 (24.3)
DM	–	18 (8.9)	12 (10.8)
Hepatitis B	–	6 (3.0)	3 (2.7)
COPD	–	5 (2.5)	4 (3.6)
Others^a	–	11(5.4)	8 (7.2)

Notes: All costs are in United States dollars. Column 2 is a subgroup of column 1, and column 3 is a subgroup of column 2. ^aOthers: in group 2, 11 patients included gastritis (n=3), uarthritis (n=3), hypertension (n=2), hyperuricemia (n=2), coronary heart disease (n=1). In group 3, 8 patients included gastritis (n=2), uarthritis (n=2), hypertension (n=1), hyperuricemia (n=2), coronary heart disease (n=1).

Abbreviations: DOT, directly observed treatment; IQR, interquartile range; SD, standard deviation; MDR-TB, multidrug-resistant tuberculosis; NRCMS, New Rural Cooperative Medical Scheme; OOP, out-of-pocket; UEBMI, Urban Employee Basic Medical Insurance; URBMI, Urban Resident Basic Medical Insurance; DM, diabetes; COPD, chronic obstructive pulmonary disease.

Table 3 Frequency Of Treatment Interruption And Main Reason For Serious Interruption By Specific Drug Received (n=202 Patients)

Type Of Interruption And Specific Drug Interrupted	Number Of Patients Under Treatment By Drug Received	Number Of Patients With Interruption n (%) (a=b+c)	Duration Of Interruptionn (%)		Main Reason For Serious Interruption, n (%)
			Short Interruption (1–14 Days) (b)	Serious interruption (>14 days) (c=d+e+f)	Adverse Drug Reaction^a (d)	Financial Hardship (e)	Other^b (f)
Overall	202	134 (66.3)	76 (37.6)	58 (28.7)	41 (20.3)	11 (5.4)	6 (3.0)
Single drug interruption	202	48 (23.8)	20 (9.9)	28 (13.9)	23 (11.4)	5 (2.5)	0 (0.0)
Amikacin	202	37 (18.3)	16 (7.9)	21 (10.4)	21 (10.4)	0 (0.0)	0 (0.0)
Cycloserine	59	6 (10.2)	1 (1.7)	5 (8.5)	0 (0.0)	5 (8.5)	0 (0.0)
Pyrazinamide	169	4 (2.4)	2 (1.2)	2 (1.2)	2 (1.2)	0 (0.0)	0 (0.0)
Amoxicillin/Clavulanate	35	1 (2.9)	1 (2.8)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Completely drug interruption	202	86 (42.6)	56 (27.7)	30 (14.9)	18 (8.9)	6 (3.0)	6 (3.0)

Notes: ^aAdverse drug reaction: hepatotoxicity (n=13), hematoma/pain at the injection site (n=12), ototoxicity (n=9), gastrointestinal disturbance (n=4), erythra (n=2), and dizziness (n=1). ^bOthers include feeling better (n=3), no confidence in treatment (n=2), and insufficient drug (n=1).

Table 4 Predictors Of Serious Treatment Interruption By Univariate And Multivariate Analysis

Characteristic	Total N (%)	Duration Of Interruption		P Value	Adjusted OR (95% CI)	P-Value (LR Test)
		0–14 Days	>14 days
Total	202 (100.0)	144 (71.3)	58 (28.7)
Gender				0.677	–	–
Female	67 (33.2)	46 (31.9)	21 (36.2)
Male	135 (66.8)	98 (68.1)	37 (63.8)
Age (years)				0.189		0.497
14–25	47 (23.3)	37 (25.7)	10 (17.2)		Ref
25–59	134 (66.3)	95 (66.0)	39 (67.2)		1.23 (0.52–2.89)
≥ 60	21 (10.4)	12 (8.3)	9 (15.5)		2.06 (0.62–6.92)
Marital status				0.355	–	–
Single	78 (38.6)	59 (41)	19 (32.8)
Married	124 (61.4)	85 (59)	39 (67.2)
Education level				0.578	–	–
Primary school or less	60 (29.7)	43 (29.9)	17 (29.3)
Middle school	68 (33.7)	49 (34.0)	19 (32.8)
High school	55 (27.2)	41 (28.5)	14 (24.1)
University	19 (9.4)	11 (7.6)	8 (13.8)
Occupational status after diagnosis				0.713	–	–
Still working	62 (30.7)	45 (31.2)	17 (29.3)
Lost job or could not work	103 (51.0)	71 (49.3)	32 (55.2)
Student/unemployed	37 (18.3)	28 (19.4)	9 (15.5)
In debt due to MDR-TB				1.000	–	–
Yes	120 (59.4)	86 (59.7)	34 (58.6)
No	82 (40.6)	58 (40.3)	24 (41.4)
Weight at baseline				0.246	–	–
≥50kg	119 (58.9)	89 (61.8)	30 (51.7)
<50kg	83 (41.1)	55 (38.2)	28 (48.3)
Duration of treatment (months)					–	–
1–11	60 (29.7)	41 (28.5)	19 (32.8)	0.665
12–24	142 (70.3)	103 (71.5)	39 (67.2)
Underwent DOT				1	–	–
Yes	56 (27.7)	40 (27.8))	16 (27.6)
No	146 (72.3)	104 (72.2)	42 (72.4)
Monthly OOP drug expenses (US$)				0.005		0.020
≤ 250	145 (71.8)	112 (77.8)	33 (56.9)		Ref
>250	57 (28.2)	32 (22.2)	25 (43.1)		2.27 (1.14–4.50)
Baseline co-morbidity				0.002		0.017
No	162 (80.2)	124 (86.1)	38 (65.5)		Ref
Yes	40 (19.8)	20 (13.9)	20 (34.5)		2.53 (1.19–5.38)
Any ADRs during treatment				<0.001		0.003
No	98 (48.5)	82 (56.9)	16 (27.6)		Ref
Yes	104 (51.5)	62 (43.1)	42 (72.4)		2.82 (1.41–5.61)

Abbreviations: ADRs, adverse drug reactions; DOT, directly observed treatment; MDR-TB, multidrug-resistant tuberculosis; OOP, out-of-pocket; OR, odds ratio; CI, confidence interval; LR test, likelihood ratio test; ref, reference group.

Table 5 Agreement Between Self-Report And Pill Counts By Drug Received

Amikacin (n=32)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	19	0	0	19 (59.4)
	Correctly used	1	7	0	8 (25.0)
	Overused	0	0	5	5 (15.6)
	Total (n, %)	20 (62.5)	7 (21.9)	5 (15.6)	32 (100.0)
	Kappa = 0.95
Levofloxacin (n=109)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	59	2	0	61 (56.0)
	Correctly used	5	30	0	35 (32.1)
	Overused	0	1	12	13 (11.9)
	Total (n, %)	64 (58.7)	33 (30.3)	12 (11.0)	109 (100.0)
	Kappa = 0.88
Prothionamide (n=106)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	56	2	0	58 (54.7)
	Correctly used	10	26	5	41 (38.7)
	Overused	2	0	5	7 (6.6)
	Total (n, %)	68 (64.2)	28 (26.4)	10 (9.4)	106 (100.0)
	Kappa = 0.69
Pyrazinamide (n=105)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	63	1	0	64 (61.0)
	Correctly used	8	16	11	35 (33.3)
	Overused	0	1	5	6 (5.7)
	Total (n, %)	71 (67.6)	18 (17.1)	16 (15.2)	105 (100.0)
	Kappa = 0.69
Ethambutol (n=92)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	49	3	0	52 (56.5)
	Correctly used	4	23	7	34 (37.0)
	Overused	0	0	6	6 (6.5)
	Total (n, %)	53 (57.6)	26 (28.3)	13 (14.1)	92 (100.0)
	Kappa = 0.78
P-aminosalicylic acid (n=82)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	42	3	3	48 (58.5)
	Correctly used	10	14	3	27 (33.0)
	Overused	0	2	5	7 (8.5)
	Total	52 (63.4)	19 (23.2)	11 (13.4)	82 (100.0)
	Kappa = 0.57
Cycloserine (n=34)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	14	1	0	15 (44.1)
	Correctly used	4	11	2	17 (50.0)
	Overused	0	1	1	2 (5.9)
	Total (n, %)	18 (53.0)	13 (38.2)	3 (8.8)	34 (100)
	Kappa = 0.63
Amoxicillin/ Clavulanate (n=32)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	15	1	0	16 (50.0)
	Correctly used	2	10	0	12 (37.5)
	Overused	0	0	4	4 (12.5)
	Total (n, %)	17 (53.1)	11 (34.4)	4 (12.5)	32 (100.0)
	Kappa = 0.87
Clofazimine (n=11)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	3	0	0	3 (27.3)
	Correctly used	2	5	1	8 (72.7)
	Overused	0	0	0	0 (0.0)
	Total (n, %)	5 (45.5)	5 (45.5)	1 (9.1)	11 (100.0)
	Kappa = 0.52
Moxifloxacin (n=6)		Pill count
	Self-report	Underused	Correctly used	Overused	Total (n, %)
	Underused	2	0	0	2 (33.3)
	Correctly used	0	3	0	3 (50.0)
	Overused	0	1	0	1 (16.7)
	Total (n, %)	2 (33.3)	4 (66.7)	0 (0.0)	6 (100.0)
	Kappa = 0.73

Patients (n=111)		Pill count
	Self-report	Correctly used	Only underuse	Only overuse	Both	Total (n, %)
	Correctly used	4	2	1	1	8 (7.2)
	Only underuse	1	53	0	9	63 (56.8)
	Only overuse	0	1	5	0	6 (5.4)
	Both	1	4	1	28	34 (30.6)
	Total (n, %)	6 (5.4)	60 (54.1)	7 (6.3)	38 (34.2)	111 (100.0)
	Kappa = 0.66

Notes: For k table, the row-wise gives self-report data; the column-wise gives pill count data. For each sub-table, the values in the diagonal cells from left upper corner to right lower corner indicate the number of subjects with agreement in assessment by these two methods.

The list of medicines for national basic medical insurance, industrial injury insurance and maternity insurance. Available from: http://www.nhsa.gov.cn/art/2019/8/20/art_37_1666.html. Accessed 913, 2019

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Policy interpretation of the work plan for adjusting the national directory of insured drugs in 2019. Available from: http://www.nhsa.gov.cn/art/2019/4/17/art_38_1212.html. Accessed 913, 2019

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