In vitro Synergism of Six Antituberculosis Agents Against Drug-Resistant Mycobacterium tuberculosis Isolated from Retreatment Tuberculosis Patients

Figures & data

Table 1 The Checkerboard Titration Arrangement on 96-Well Plates for Triple-Drug Susceptibility Testing

	1	2	3	4	5	6	7	8	9	10	11	12
A	No drug	Pa0.0075	P0.015	P0.03	P0.06	P0.125	P0.25	P0.5	P1	P2	P4	P8
B	MFX0.03	P0.0075+M0.03	P0.015+M0.03	P0.03+M0.03	P0.06+M0.03	P0.125+M0.03	P0.25+M0.03	P0.5+M0.03	P1+M0.03	P2+M0.03	P4+M0.03	P8+M0.03
C	M0.06	P0.0075+M0.06	P0.015+M0.06	P0.03+M0.06	P0.06+M0.06	P0.125+M0.06	P0.25+M0.06	P0.5+M0.06	P1+M0.06	P2+M0.06	P4+M0.06	P8+M0.06
D	M0.125	P0.0075+M0.125	P0.015+M0.125	P0.03+M0.125	P0.06+M0.125	P0.125+M0.125	P0.25+M0.125	P0.5+M0.125	P1+M0.125	P2+M0.125	P4+M0.125	P8+M0.125
E	M0.25	P0.0075+M0.25	P0.015+M0.25	P0.03+M0.25	P0.06+M0.25	P0.125+M0.25	P0.25+M0.25	P0.5+M0.25	P1+M0.25	P2+M0.25	P4+M0.25	P8+M0.25
F	M0.5	P0.0075+M0.5	P0.015+M0.5	P0.03+M0.5	P0.06+M0.5	P0.125+M0.5	P0.25+M0.5	P0.5+M0.5	P1+M0.5	P2+M0.5	P4+M0.5	P8+M0.5
G	M1	P0.0075+M1	P0.015+M1	P0.03+M1	P0.06+M1	P0.125+M1	P0.25+M1	P0.5+M1	P1+M1	P2+M1	P4+M1	P8+M1
H	M2	P0.0075+M2	P0.015+M2	P0.03+M2	P0.06+M2	P0.125+M2	P0.25+M2	P0.5+M2	P1+M2	P2+M2	P4+M2	RFB/RFP

Notes: The final concentrations of RFB added to the whole plate except well A1 were 0.125, 0.25, 0.5, 1, and 2 μg/mL, while the corresponding final concentrations of RFP were 1, 2, 4, 8, and 16 μg/mL, respectively.

Table 2 Comparison of MICs for Each Drug Before and After Combinations from Dual-Drug Susceptibility Testing

Drug Combination	MIC (Mg/Liter)			P value
	50%	90%	Range
INH+RIF
INH	4	16	0.125 to 16
inh	2	8	0.125 to 16	<0.001
RIF	24	64	0.03 to 64
rif	1	32	0.03 to 64	<0.001
Pa+RFB
Pa	2	16	0.015 to 32
pa	0.5	4	0.0075 to 16	<0.001
RFB	4	8	0.0625 to 8
rfb	0.125	2	0.03125 to 4	<0.001
Pa+RFP
Pa	2	16	0.015 to 32
pa	0.25	4	0.0075 to 8	<0.001
RFP	32	64	0.5 to 64
rfp	4	16	0.25 to 16	<0.001
MXF+Pa
MXF	0.5	1	0.03 to 4
mxf	0.5	2	0.03 to 2	0.012
Pa	8	16	0.015 to 32
pa	0.0075	4	0.0075 to 16	<0.001

Notes: INH, MIC of INH tested alone; inh, MIC of INH tested with RIF in combination; RIF, MIC of RIF tested alone; rif, MIC of RIF tested with INH in combination. The rest of the upper- and lower-case letters are the same (dual-drug susceptibility testing); data in bold indicate that the P values were statistically significant.

Table 3 Distribution and Comparison of FICI of 90 Strains from Four Dual-Drug Combinations

FICI Value	INH+RIF^a	Pa+RFB^b	Pa+RFP^c	MXF+Pa^d
≤0.5	10 (11.1)^e	26 (28.9)	45 (50.0)	5 (5.6)
0.5< and ≤4	80 (88.9)	62 (68.9)	45 (50.0)	85 (94.4)
>4	0	2 (2.2)	0	0

Notes: P value for a vs b comparison was 0.0127; P value for a vs c comparison was <0.0001; P value for a vs d comparison was 0.2807; P value for b vs c comparison was 0.0021; P value for b vs d comparison was 0.0004; P value for c vs d comparison was <0.0001; e, the data in and outside the brackets represented the percentages and frequencies.

Table 4 Comparison of MICs for Each Drug Before and After Combinations from Triple-Drug Susceptibility Testing

Drug Combination	MIC (Mg/Liter)			P value
	50%	90%	Range
MXF+Pa+RFB
MXF	0.5	1	0.03 to 4
mxf	0.25	2	0.03 to 2	0.129
Pa	2	16	0.015 to 32
pa	0.0075	0.5	0.0075 to 16	<0.001
RFB	4	8	0.0625 to 8
rfb	0.125	0.2375	0.03125 to 1	<0.001
MXF+Pa+RFP
MXF	0.5	1	0.03 to 4
mxf	0.25	2	0.03 to 2	0.719
Pa	2	16	0.015 to 32
pa	0.0225	4	0.0075 to 16	<0.001
RFP	32	64	0.5 to 64
rfp	1	1	0.5 to 4	<0.001

Notes: MXF, MIC of MXF tested alone; mxf, MIC of MXF tested with the combination of Pa with RFB; Pa, MIC of Pa tested alone; pa, MIC of Pa tested with the combination of MXF with RFB; RFB, MIC of RFB tested alone; rfb, MIC of RFB tested with the combination of MXF with Pa; The rest of the upper- and lower-case letters are the same (triple-drug susceptibility testing); data in bold indicate that the P values were statistically significant.

Table 5 Distribution and Comparison of FICI of 90 Strains from Two Triple-Drug Combinations

FICI Value	MXF+Pa+RFB^a	MXF+Pa+RFP^b
≤0.75	16 (17.8)^c	21 (23.3)
0.75< and ≤4	64 (71.1)	57 (63.3)
>4	10 (11.1)	12 (13.3)

Notes: P value for a vs b comparison was 0.5319; c, the data in and outside the brackets represented the percentages and frequencies.

Table 6 Distribution and Comparison of FICI of 54 XDR-MTB Strains from Four Dual-Drug Combinations

FICI Value	INH+RIF^a	Pa+RFB^b	Pa+RFP^c	MXF+Pa^d
≤0.5	6 (11.1)^e	11 (20.4)	28 (51.9)	3 (5.6)
0.5< and ≤4	48 (88.9)	41 (75.9)	26 (48.1)	51 (94.4)
>4	0	2 (3.7)	0	0

Notes: P value for a vs b comparison was 0.4658; P value for a vs c comparison was <0.0001; P value for a vs d comparison was 0.4862; P value for b vs c comparison was 0.0004; P value for b vs d comparison was 0.0001; P value for c vs d comparison was <0.0001; e, the data in and outside the brackets represented the percentages and frequencies.

Table 7 Distribution and Comparison of FICI of 54 XDR-MTB Strains from Two Triple-Drug Combinations

FICI Value	MXF+Pa+RFB^a	MXF+Pa+RFP^b
≤0.75	8 (14.8)^c	9 (16.7)
0.75< and ≤4	38 (70.4)	37 (68.5)
>4	8 (14.8)	8 (14.8)

Notes: P value for a vs b comparison was 0.9646; c, the data in and outside the brackets represented the percentages and frequencies.

Table 8 Distribution and Comparison of FICI of 29 MDR-MTB Strains from Four Dual-Drug Combinations

FICI Value	INH+RIF^a	Pa+RFB^b	Pa+RFP^c	MXF+Pa^d
≤0.5	4 (13.8)^e	9 (31.0)	10 (34.5)	1 (3.4)
0.5< and ≤4	25 (86.2)	20 (69.0)	19 (65.5)	28 (96.6)
>4	0	0	0	0

Notes: P value for a vs b comparison was 0.2079; P value for a vs c comparison was 0.125; P value for a vs d comparison was 0.1417; P value for b vs c comparison was >0.99; P value for b vs d comparison was 0.015; P value for c vs d comparison was 0.0074; e, the data in and outside the brackets represented the percentages and frequencies.

Table 9 Distribution and Comparison of FICI of 29 MDR-MTB Strains from Two Triple-Drug Combinations

FICI Value	MXF+Pa+RFB^a	MXF+Pa+RFP^b
≤0.75	7 (24.1)^c	10 (34.5)
0.75< and ≤4	20 (69.0)	15 (51.7)
>4	2 (6.9)	4 (13.8)

Notes: P value for a vs b comparison was 0.3847; c, the data in and outside the brackets represented the percentages and frequencies.