Table 2.
Treatment Outcomes in Relation to the Pattern of Initial and Acquired Resistance to Second-Line Injectable Drugs and Fluoroquinolones, the Number of Companion Drugs with Resistance, and Resistance to Individual Antituberculosis Drugs Among 1244 Patients With Multidrug-Resistant Tuberculosis in 9 Countries, 2005–2010
| Drug Resistance Pattern | Successful vs Poor Outcomes Among Patients With Known Outcomes (n = 973) |
Patients With Known Outcomes vs Patients Lost To Follow-Up (n = 1205)a |
|||||
|---|---|---|---|---|---|---|---|
| Successful Outcomes, No. (Row %) | Poor Outcomes, No. (Row %) | P Value for Trend | Risk Ratio (95% CI) for Treatment Success | Total With Known Outcome, No. (Row %) | Lost to Follow-up, No. (Row %) | P Value for Trend | |
| Drug resistance pattern in 5 broad categories of initial and acquired resistance | |||||||
| Drug resistance patternb | |||||||
| Plain MDR tuberculosis | 591 (85.8) | 98 (14.2) | <.001 | Reference | 689 (79.9) | 173 (20.1) | .27 |
| Initial pre-XDR tuberculosis | 92 (69.7) | 40 (30.3) | 0.81 (.72–.91) | 132 (81.0) | 31 (19.0) | ||
| Acquired pre-XDR tuberculosis | 15 (37.5) | 25 (62.5) | 0.44 (.29–.65) | 40 (88.9) | 5 (11.1) | ||
| Initial XDR tuberculosis | 17 (29.3) | 41 (70.7) | 0.34 (.23–.51) | 58 (84.1) | 11 (15.9) | ||
| Acquired XDR tuberculosis | 7 (13.0) | 47 (87.0) | 0.15 (.08–.30) | 54 (81.8) | 12 (18.2) | ||
| Drug resistance pattern including all 9 logical combinations of initial and acquired resistance to SLIs and FQs | |||||||
| Plain MDR | |||||||
| No acquired resistance | 591 (85.8) | 98 (14.2) | <.001 | Reference | 689 (79.9) | 173 (20.1) | .24 |
| Initial Pre-XDR | |||||||
| Initial SLI resistance | 57 (71.3) | 23 (28.8) | 0.83 (.72–.96) | 80 (79.2) | 21 (20.8) | ||
| Initial FQ resistance | 35 (67.3) | 17 (32.7) | 0.78 (.65–.95) | 52 (83.9) | 10 (16.1) | ||
| Acquired pre-XDR | |||||||
| Acquired SLI resistance | 10 (43.5) | 13 (56.5) | 0.51 (.32–.81) | 23 (88.5) | 3 (11.5) | ||
| Acquired FQ resistance | 5 (29.4) | 12 (70.6) | 0.34 (.16–.72) | 17 (89.5) | 2 (10.5) | ||
| Initial XDR | |||||||
| Initial XDR tuberculosis | 17 (29.3) | 41 (70.7) | 0.34 (.23–.51) | 58 (84.1) | 11 (15.9) | ||
| Acquired XDR | |||||||
| Acquired SLI and FQ resistance | 2 (20.0) | 8 (80.0) | 0.23 (.07–.81) | 10 (76.9) | 3 (23.1) | ||
| Acquired SLI resistance | 1 (12.5) | 7 (87.5) | 0.15 (.02–.91) | 36 (83.7) | 7 (16.3) | ||
| Acquired FQ resistance | 4 (11.1) | 32 (88.9) | 0.13 (.05–.33) | 8 (80.0) | 2 (20.0) | ||
| Resistance to companion drugs among patients with plain MDR tuberculosis and those with additional resistance to SLI or FQ | |||||||
| No. of companion drugs with resistance in patients with plain MDRc | |||||||
| 0 | 207 (87.7) | 29 (12.3) | .10 | Reference | 236 (78.1) | 66 (21.8) | .13 |
| 1 | 288 (86.2) | 46 (13.8) | 0.98 (.92–1.05) | 334 (79.5) | 86 (20.5) | ||
| ≥2 | 96 (80.7) | 23 (19.3) | 0.92 (.83–1.02) | 119 (85.0) | 21 (15.0) | ||
| No. of companion drugs with resistance in patients with any SLI or FQ resistance | |||||||
| 0 | 43 (58.1) | 31 (41.9) | .02 | Reference | 74 (91.4) | 7 (8.6) | .050 |
| 1 | 61 (43.9) | 78 (56.1) | 0.76 (.58–.98) | 139 (80.3) | 34 (19.6) | ||
| ≥2 | 27 (38.0) | 44 (62.0) | 0.65 (.46–.93) | 71 (79.8) | 18 (20.2) | ||
| Resistance to individual drugs | |||||||
| Ethambutol | |||||||
| Susceptible | 296 (78.9) | 79 (21.1) | .008 | 1.11 (1.03–1.19) | 162 (20.0) | 648 (80.0) | .35 |
| Resistant | 426 (71.2) | 172 (28.8) | 70 (17.7) | 325 (82.3) | |||
| Streptomycin | |||||||
| Susceptible | 247 (78.9) | 66 (21.1) | .02 | 1.10 (1.02–1.18) | 36 (21.6) | 131 (78.4) | .98 |
| Resistant | 475 (72.0) | 185 (28.0) | 45 (21.4) | 165 (78.6) | |||
| Pyrazinamided | |||||||
| Susceptible | 270 (84.9) | 48 (15.1) | <.001 | 1.26 (1.16–1.37) | 318 (76.3) | 99 (23.7) | .18 |
| Resistant | 254 (67.5) | 122 (32.4) | 376 (82.6) | 79 (17.4) | |||
| Unknown | 198 (71.0) | 81 (29.0) | 279 (83.8) | 54 (16.2) | |||
| Kanamycin | |||||||
| Susceptible | 649 (80.0) | 162 (20.0) | <.001 | 1.78 (1.49–2.11) | 36 (21.6) | 131 (78.4) | .54 |
| Resistant | 73 (45.1) | 89 (54.9) | 129 (19.4) | 535 (80.6) | |||
| Amikacin | |||||||
| Susceptible | 663 (79.6) | 170 (20.4) | <.001 | 1.89 (1.55–2.30) | 36 (21.6) | 131 (78.4) | .11 |
| Resistant | 59 (42.1) | 81 (57.9) | 30 (15.1) | 169 (84.9) | |||
| Capreomycin | |||||||
| Susceptible | 692 (79.3) | 181 (20.7) | <.001 | 2.64 (1.95–3.57) | 36 (21.6) | 131 (78.4) | .26 |
| Resistant | 30 (30.0) | 70 (70.0) | 48 (17.3) | 230 (82.7) | |||
| ≥1 SLI | |||||||
| Susceptible | 644 (80.6) | 155 (19.4) | <.001 | 1.80 (1.52–2.13) | 36 (21.6) | 131 (78.4) | .42 |
| Resistant | 78 (44.8) | 96 (55.2) | 196 (18.9) | 842 (81.1) | |||
| All 3 SLIs | |||||||
| Susceptible | 697 (78.8) | 188 (21.2) | <.001 | 2.78 (2.0–3.87) | 885 (81.0) | 207 (19.0) | .41 |
| Resistant | 25 (28.4) | 63 (71.6) | 88 (77.9) | 25 (22.1) | |||
| FQs | |||||||
| Susceptible | 669 (78.3) | 186 (21.8) | <.001 | 1.74 (1.42–2.13) | 24 (16.2) | 124 (83.8) | .32 |
| Resistant | 53 (44.9) | 65 (55.1) | 208 (19.7) | 849 (80.3) | |||
| Thioamides | |||||||
| Susceptible | 591 (75.7) | 190 (24.3) | .04 | 1.11 (1.0–1.23) | 40 (16.3) | 206 (83.7) | .18 |
| Resistant | 131 (68.2) | 61 (31.8) | 192 (20.0) | 767 (80.0) | |||
| Para-aminosalicylic acid | |||||||
| Susceptible | 676 (76.0) | 213 (24.0) | <.001 | 1.39 (1.14–1.69) | 119 (21.0) | 448 (79.0) | .15 |
| Resistant | 46 (54.8) | 38 (45.2) | 113 (17.7) | 525 (82.3) | |||
Abbreviations: CI, confidence interval; FQ, fluoroquinolone; MDR, multidrug-resistant; SLI, second-line injectable drug; XDR, extensively drug-resistant.
a Risk ratios comparing patients with known outcomes versus those patients lost to follow-up are not presented because most of the differences were not statistically significant.
b Pre-XDR tuberculosis was defined as MDR tuberculosis plus resistance to either an SLI or an FQ but not both, irrespective of resistance to other drugs; XDR tuberculosis, as MDR tuberculosis plus resistance to an SLI and an FQ, irrespective of resistance to other drugs.
c Companion drugs include ethambutol, thioamides (prothionamide or ethionamide, analyzed together as the same drug), serine analogues (cycloserine or terizidone).
d Pyrazinamide phenotypic drug susceptibility testing (DST) and pncA gene sequencing at the Centers for Disease Control and Prevention (CDC) have not yet been completed; therefore, all available phenotypic DST results for pyrazinamide from both CDC and local laboratories have been combined; all phenotypic DST for pyrazinamide was determined using the Mycobacterial Growth Indicator Tube 960 method.