Performance Comparison of Three Rapid Tests for the Diagnosis of Drug-Resistant Tuberculosis

<div><p>Background</p><p>The aim of this study was to compare the performance of several recently developed assays for the detection of multi- and extensively drug-resistant tuberculosis (M/XDR-TB) in a large, multinational field trial.</p><p>Methods</p><p>Samples from 1,128 M/XDR-TB suspects were examined by Line Probe Assay (LPA), Pyrosequencing (PSQ), and Microscopic Observation of Drug Susceptibility (MODS) and compared to the BACTEC MGIT960 reference standard to detect M/XDR-TB directly from patient sputum samples collected at TB clinics in India, Moldova, and South Africa.</p><p>Results</p><p>Specificity for all three assays was excellent: 97–100% for isoniazid (INH), rifampin (RIF), moxifloxacin (MOX) and ofloxacin (OFX) and 99–100% for amikacin (AMK), capreomycin (CAP) and kanamycin (KAN) resistance. Sensitivities were lower, but still very good: 94–100% for INH, RIF, MOX and OFX, and 84–90% for AMK and CAP, but only 48–62% for KAN. In terms of agreement, statistically significant differences were only found for detection of RIF (MODS outperformed PSQ) and KAN (MODS outperformed LPA and PSQ) resistance. Mean time-to-result was 1.1 days for LPA and PSQ, 14.3 days for MODS, and 24.7 days for MGIT.</p><p>Conclusions</p><p>All three rapid assays evaluated provide clinicians with timely detection of resistance to the drugs tested; with molecular results available one day following laboratory receipt of samples. In particular, the very high specificity seen for detection of drug resistance means that clinicians can use the results of these rapid tests to avoid the use of toxic drugs to which the infecting organism is resistant and develop treatment regiments that have a higher likelihood of yielding a successful outcome.</p></div

Flowchart of patient enrollment, clinical sample processing for Line Probe Assay (LPA), Microscopic Observation of Drug Susceptibility (MODS), and Pyrosequencing (PSQ) for seven anti-TB drugs: isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin (AMK), kanamycin (KAN), and capreomycin (CAP).

<p>Includes one null PSQ sample result (denoted as 'a'). R: Resistant, S: Susceptible, and I: Indeterminate.</p

Sensitivity, specificity and percent agreement between three rapid drug susceptibility tests and MGIT for seven drugs: isoniazid (INH), rifampin (RIF), moxifloxacin (MOX), ofloxacin (OFX), amikacin (AMK), kanamycin (KAN), and capreomycin (CAP).

<p>Mean values and 95% confidence intervals for each comparison are represented in the figure; full data is included as a supplementary table.</p

Time to Test Results (TTR).

<p>Criteria for inclusion in the time-to-result calculations: tests worked for all drugs tested on the first attempt unless otherwise noted. Only results from the culture positive pooled (P1) samples were used. For the growth-based assays MGIT DST and MODS, TTR was the period from sample processing through test completion. For the genotypic tests, TTR was sample processing through DNA extraction and PCR/test set up through completion, excluding time DNA was stored for batching or lab convenience.</p