Waste to worth: diagnostic accuracy of Xpert MTB/XDR on contaminated liquid cultures to salvage the detection of drug-resistant tuberculosis.

Unlabelled: Mycobacterium Growth Indicator Tube (MGIT) 960 culture is critical for tuberculosis (TB) drug susceptibility testing (DST) but is vulnerable to contamination. We evaluated the accuracy of Xpert MTB/XDR, a molecular DST for isoniazid, fluoroquinolone, amikacin, and ethionamide, on to-be-discarded contaminated growth. Xpert MTB/XDR was applied to acid-fast-bacilli-negative, contaminated cultures from sputum from people with rifampicin-resistant TB when Xpert MTB/XDR on sputum was unsuccessful (not resistant or susceptible for all drugs), either at diagnosis (Cohort A) or during treatment monitoring (Cohort B).

Waste to Worth: A diagnostic accuracy of Xpert MTB/XDR on contaminated liquid cultures to salvage the detection of drug-resistant tuberculosis.

Introduction: Mycobacterium Growth Indicator Tube (MGIT) 960 culture is critical for tuberculosis (TB) drug susceptibility testing (DST) but vulnerable to contamination. We evaluated the accuracy of Xpert MTB/XDR, a molecular DST for isoniazid, fluoroquinolone, amikacin, and ethionamide, on to-be-discarded contaminated growth.

Methods: Xpert MTB/XDR was applied to acid-fast bacilli-negative contaminated cultures from sputum from people with rifampicin-resistant TB when Xpert MTB/XDR on sputum was unsuccessful (not resistant or susceptible for all drugs) 1) at diagnosis (Cohort A) or 2) during treatment monitoring (Cohort B).

Diagnostic Accuracy of LiquidArray MTB-XDR VER 1.0 for the Detection of Mycobacterium tuberculosis Complex, Fluoroquinolone, Amikacin, Ethambutol, and Linezolid Susceptibility.

Background: Drug susceptibility testing (DST) is essential for starting people on effective tuberculosis (TB) regimens. No published data exist for the high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects Mycobacterium tuberculosis complex (MTBC) and fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility (the latter 2 have no rapid DSTs available).

Methods: We enrolled people (N = 720) with presumptive TB who provided 2 sputum samples for an Xpert MTB/RIF Ultra assay and a culture (MTBC reference standard).

C-Reactive Protein-based Screening of People with Tuberculosis Symptoms: A Diagnostic Accuracy Study.

C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV. However, its performance among people without HIV and in diverse settings is unknown. In a multicountry study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ⩾ 90%, specificity ⩾ 70%) for an effective TB screening test.

Diagnostic accuracy of LiquidArray MTB-XDR VER1.0 for the detection of complex, fluoroquinolone, amikacin, ethambutol, and linezolid susceptibility.

Drug susceptibility testing (DST) is essential for effectively starting people on effective tuberculosis (TB) regimens. No accuracy data exists for the new high-throughput LiquidArray MTB-XDR (LA-XDR) test, which detects complex (MTBC) and susceptibility to the fluoroquinolones, amikacin, ethambutol, and linezolid (the latter two drugs have no rapid molecular DSTs available). We enrolled (n=720) people with presumptive TB who provided two sputa for Xpert MTB/RIF Ultra and culture (MTBC reference standard).

An independent, multi-country head-to-head accuracy comparison of automated chest x-ray algorithms for the triage of pulmonary tuberculosis.

Background: Computer-aided detection (CAD) algorithms for automated chest X-ray (CXR) reading have been endorsed by the World Health Organization for tuberculosis (TB) triage, but independent, multi-country assessment and comparison of current products are needed to guide implementation.

Methods: We conducted a head-to-head evaluation of five CAD algorithms for TB triage across seven countries. We included CXRs from adults who presented to outpatient facilities with at least two weeks of cough in India, Madagascar, the Philippines, South Africa, Tanzania, Uganda, and Vietnam.

C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study.

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown.

Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study.

Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART).

Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study.

Background: Bedaquiline is a life-saving tuberculosis drug undergoing global scale-up. People at risk of weak tuberculosis drug regimens are a priority for novel drug access despite the potential source of Mycobacterium tuberculosis-resistant strains. We aimed to characterise bedaquiline resistance in individuals who had sustained culture positivity during bedaquiline-based treatment.

Xpert MTB/RIF Ultra on contaminated liquid cultures for tuberculosis and rifampicin-resistance detection: a diagnostic accuracy evaluation.

Background: Xpert MTB/RIF Ultra (Ultra) is a widely used rapid front-line tuberculosis and rifampicin-susceptibility testing. Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture is used as an adjunct but is vulnerable to contamination. We aimed to assess whether Ultra can be used on to-be-discarded contaminated cultures.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective diagnostic accuracy study.

Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection.

Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms.

Non-actionable Results, Accuracy, and Effect of First- and Second-line Line Probe Assays for Diagnosing Drug-Resistant Tuberculosis, Including on Smear-Negative Specimens, in a High-Volume Laboratory.

Background: Rapid tuberculosis (TB) drug susceptibility testing (DST) is crucial. Genotype MTBDRsl is a widely deployed World Health Organization (WHO)-endorsed assay. Programmatic performance data, including non-actionable results from smear-negative sputum, are scarce.

An All-Oral 6-Month Regimen for Multidrug-Resistant Tuberculosis: A Multicenter, Randomized Controlled Clinical Trial (the NExT Study).

Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e.

Frequent Suboptimal Thermocycler Ramp Rate Usage Negatively Impacts GenoType MTBDRsl VER 2.0 Performance for Second-Line Drug-Resistant Tuberculosis Diagnosis.

Strengthening second-line drug-resistant tuberculosis (TB) detection is a priority. GenoType MTBDRplus VER 2.0 performance is reduced with non-recommended ramp rate usage (temperature change speed between PCR cycles); however, ramp rate's effect on GenoType MTBDRsl VER 2.

Diagnostic accuracy of the FluoroType MTB and MTBDR VER 2.0 assays for the centralized high-throughput detection of Mycobacterium tuberculosis complex DNA and isoniazid and rifampicin resistance.

Objectives: To evaluate the accuracy of two new molecular diagnostic tests for the detection of drug-resistant tuberculosis, the FluoroType MTB and MTBDR VER 2.0 assays, in combination with manual and automated DNA extraction methods.

Methods: Sputa from 360 Xpert Ultra Mycobacterium tuberculosis complex (MTBC)-positive patients and 250 Xpert Ultra MTBC-negative patients were tested.

Melting the : Nondetection of Kanamycin Resistance Markers by Routine Diagnostic Tests and Identification of New Promoter Variants.

promoter mutations can confer reduced Mycobacterium tuberculosis kanamycin susceptibility. GenoType MTBDR a widely used assay evaluating this region, wrongly classified 17/410 isolates as promoter wild type. Six out of seventeen isolates harbored mutations known to confer kanamycin resistance, and the remainder harbored either novel promoter mutations (7/11) or disputed mutations (4/11).

Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk.

Xpert MTB/RIF Ultra (Ultra) detects Mycobacterium tuberculosis and rifampicin resistance. Follow-on drug susceptibility testing (DST) requires additional sputum. Extract from the diamond-shaped chamber of the cartridge (dCE) of Ultra's predecessor, Xpert MTB/RIF (Xpert), is useful for MTBDRsl-based DST but this is unexplored with Ultra.

Detection of Second Line Drug Resistance among Drug Resistant Mycobacterium Tuberculosis Isolates in Botswana.

The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates.

Diagnostic Accuracy and Utility of FluoroType MTBDR, a New Molecular Assay for Multidrug-Resistant Tuberculosis.

Most cases of multidrug-resistant (MDR) tuberculosis (TB) are never diagnosed (328,300 of the ∼490,000 cases in 2016 were missed). The Xpert MTB/RIF assay detects resistance only to rifampin, despite ∼20% of rifampin-resistant cases being susceptible to isoniazid (a critical first-line drug). Consequently, many countries require further testing with the GenoType MTBDR assay.

Mycobacterial genomic DNA from used Xpert MTB/RIF cartridges can be utilised for accurate second-line genotypic drug susceptibility testing and spoligotyping.

Xpert MTB/RIF (Xpert) is a widely-used test for tuberculosis (TB) and rifampicin-resistance. Second-line drug susceptibility testing (DST), which is recommended by policymakers, typically requires additional specimen collection that delays effective treatment initiation. We examined whether cartridge extract (CE) from used Xpert TB-positive cartridges was, without downstream DNA extraction or purification, suitable for both genotypic DST (MTBDRplus, MTBDRsl), which may permit patients to rapidly receive a XDR-TB diagnosis from a single specimen, and spoligotyping, which could facilitate routine genotyping.

Comparative diffusion of drugs through bronchial tissue.

The purpose of the study was to investigate the molecular diffusion of drugs across porcine bronchial tissue. Using an in vitro flow-through diffusion system, a series of model compounds were tested. These included theophylline, caffeine, theobromine, enprofylline, salbutamol, ipratropium bromide, and trimethoprim.