Background
Methods
Study design and specimen inclusion criteria
Analytical testing of rifampin resistance detection performance
Clinical studies
Laboratory testing
Study number | Geographical location/collection site | Xpert MTB/RIF Assay Testing Site | Specimen Used for Xpert MTB/RIF Assay Testinga | Specimen Processing for Smear & Culture | AFB Smear Method on Processed Sputuma | Culture Methoda | TB Identification Methoda | DST Methoda | |
---|---|---|---|---|---|---|---|---|---|
CS1 | Peru | NJMS | Archived (Frozen) | Raw Sputum | NALC-NaOH | ZN | LJ and MGIT | CapilliaTB-Neo | LJ Proportions |
South Africa, Vietnam, Bangladeshb,c | NJMS | Archived (Frozen) | Raw Sputum | NALC- NaOH | ZN | LJ and MGIT | GenoType® MTBC | MGIT SIRE | |
CS2 | New York | New York | Archived (4 °C) | Pellet | NaOH | ZN | 7H10 and MGIT | In house RT-PCR | MB Proportions |
CS3 | New York | New York | Fresh | Pellet | NaOH | ZN | 7H10 and MGIT | In house RT-PCR | MB Proportionsd |
California | California | Fresh | Pellet | NALC- NaOH | AuRho | 7H10 and MGIT | AccuProbe MTBC | MB Proportionsd | |
Florida | Florida | Fresh | Pellet or Raw Sputum | NALC-NaOH | AccuProbe | MB Proportionsd | |||
AuO + ZN | LJ and MGIT | AccuProbe MTBC | |||||||
CS4 | Tijuana, Mexico | California | Fresh | Raw Sputum | NALC-NaOH | AuRho | LJ and MGIT | AccuProbe MTBCe | MB Proportionse |
Clinical study case definitions
Statistical analysis
Results
Specimen inclusion and clinical demographics
Analytical study
Clinical studies
Xpert performance
Analytical study
a. Analytical study | |||
DST Result | Xpert MTB/RIF assay result | Number | Sequence resulta |
RIF-resistant | MTB not detected | 3 | MTB |
RIF-susceptible | MTB not detected | 1 | MTB |
RIF-resistant | RIF Resistance not detected | 2 | 2 of 2 wild type rpoB core |
RIF-susceptible | RIF Resistance detected | 9 | 8 of 9 with resistance associated mutations in rpoB core: three with 531 ttg, three with 526 tgc, one with 516 gtc, one with 526 ctc 1 of 9 wild type rpoB core |
b. Combined clinical studies | |||
Culture/DST result | Xpert MTB/RIF assay result | Number | Bi-directional sequencing |
Smear-positive specimens
| |||
MTB positive | MTB not detected | 1 | MTB |
MTB negativeb | MTB detected | 1 | N/A |
Smear-negative specimens
| |||
MTB positive | MTB not detected | 28 | MTB |
MTB negativec | MTB detected | 7 | N/A |
Rifampin resistance results
| |||
MTB positive/RIF- resistant | MTB detected; RIF Resistance NOT detected | 1 | Resistance associated mutation in rpoB core: 531 ttg with evidence of wild type mixture |
MTB positive/RIF- susceptible | MTB detected; RIF Resistance detected | 4 | 2 of 4 with resistance associated mutations in rpoB core: both with 533 ccg |
2 of 4 with susceptible associated rpoB core: one wild-type and one 514 ttt (silent) mutation. |
Clinical studies
Subject demographics
Xpert assay performance for detection of MTB
AFB Smear-positive subjects | AFB Smear-negative subjects | All samples | |
---|---|---|---|
Specimen Collection Methoda | |||
Expectorated Sputum (n = 535) | |||
Sensitivity | 99.6% (271/272)b | 79.0% (75/95)c | 94.3% (346/367)d |
95% CI: 97.9 – 99.9% | 95% CI: 69.7 – 85.9% | 95% CI: 91.4 – 96.2% | |
Specificity | 97.6% (164/168)b | ||
95% CI: 94.0 – 99.1% | |||
Induced Sputum (n = 234) | |||
Sensitivity | 100% (15/15)b | 40.0% (4/10)c | 76% (19/25)d |
95% CI: 79.6 – 100% | 95% CI: 16.8 – 68.7% | 95% CI: 56.6 – 85.5% | |
Specificity | 99.0% (207/209)b | ||
95% CI: 96.6 – 99.7% | |||
Specimen Type | |||
Raw Sputum (n = 606) | |||
Sensitivity | 99.7% (285/286)b | 79.4% (77/97)e | 94.5% (362/383)b |
95% CI: 98.0 – 99.9% | 95% CI: 70.3 – 86.2% | 95% CI: 91.8% - 96.4% | |
Specificity | 97.8% (218/223)b | ||
95% CI: 94.9 – 99.0% | |||
Concentrated Sputum Sediment (n = 490) | |||
Sensitivity | 100% (65/65)b | 60.0% (12/20)e | 90.6% (77/85)b |
95% CI: 94.4 – 100% | 95% CI: 38.7 – 78.1% | 95% CI: 82.5% - 95.2% | |
Specificity | 99.3% (402/405)b | ||
95% CI: 97.8 – 99.7% |
Xpert assay performance for detection of RIF resistance
Positive predictive value (PPV) and negative predictive value (NPV) for Xpert detection of MTB and RIF resistance
Prevalence of MTB culture positive | Probability of MTB culture positive among | Probability of MTB culture negative among | |
---|---|---|---|
Xpert MTB detected AFB Smear Pos. | Xpert MTB detected AFB Smear Neg. | Xpert MTB not detected | |
1% | 82.9 | 14.4 | 99.9 |
2% | 90.8 | 25.4 | 99.9 |
3% | 93.7 | 34.1 | 99.8 |
4% | 95.2 | 41.0 | 99.7 |
5% | 96.2 | 46.8 | 99.7 |
10% | 98.2 | 65.0 | 99.3 |
11.8%
|
98.5%
|
69.1%
|
99.2%
|
20% | 99.2 | 80.7 | 98.5 |
40% | 99.7 | 91.8 | 96.1 |
50% | 99.8 | 94.4 | 94.2 |
Prevalence of MTB culture positive | Prevalence of RIF resistance among MTB culture positive | Probability of RIF Resistance among Xpert results “MTB detected RIF Resistance detected” | Percent of Xpert results “MTB detected RIF Resistance detected” in the population | Probability of RIF Resistance among Xpert results “MTB detected, RIF Resistance not detected” |
---|---|---|---|---|
5% | 1.0% | 48.4% | 0.09% | 0.04% |
1.5% | 58.6% | 0.11% | 0.06% | |
2.0% | 65.5% | 0.13% | 0.08% | |
10% | 91.2% | 0.47% | 0.45% | |
50% | 98.9% | 2.17% | 3.39% | |
11.8%
| 1.0% | 48.4% | 0.21% | 0.05% |
1.5%
|
58.6%
|
0.26%
|
0.07%
| |
2.0%
|
65.5%
|
0.31%
|
0.10%
| |
10% | 91.2% | 1.11% | 0.51% | |
50% | 98.9% | 5.11% | 4.16% | |
20% | 1.0% | 48.4% | 0.35% | 0.05% |
1.5% | 58.6% | 0.44% | 0.07% | |
2.0% | 65.5% | 0.52% | 0.10% | |
10% | 91.2% | 1.88% | 0.54% | |
50% | 98.9% | 8.66% | 4.46% |