Xpert MTB/RIF Ultra Assay Using Stool: an Effective Solution for Bacilli Identification from Adult Pulmonary Tuberculosis Suspects without Expectorated Sputum.

This study evaluated the diagnostic performance of stool-based Xpert MTB/RIF Ultra assay (Xpert-Ultra, Cepheid, USA) against other tests using respiratory tract specimens (RTS) and stool for diagnosing adult pulmonary tuberculosis. A prospective study on patients with presumptive pulmonary tuberculosis was conducted in Beijing Chest Hospital from June to November 2021. The smear test, MGIT960 liquid culture, and Xpert MTB/RIF (Xpert, Cepheid, USA) were performed simultaneously on RTS, and smear, culture Xpert, and Xpert-Ultra were performed simultaneously using stool. Patients were grouped based on the outcomes of RTS examination and other tests. In total, 130 eligible patients were enrolled that included 96 pulmonary tuberculosis and 34 non-TB patients. The sensitivity of smear, culture, Xpert, and Xpert-Ultra using stool was 10.96%, 23.28%, 60.27%, and 79.45%, respectively. The specificities of Xpert and Xpert-Ultra using RTS and stool were all 100% (34/34). Notably, all five confirmed cases detected by bronchoalveolar lavage fluid (BALF) examination yielded Xpert-Ultra positive outcomes with the stool specimens. Xpert-Ultra assay on stool sample harbors comparable sensitivity with Xpert on RTS. Thus, the Xpert-Ultra testing on stool specimens could be a very promising and practical strategy to improve pulmonary tuberculosis (PTB) diagnosis, especially among patients who could not expectorate sputum. IMPORTANCE This study is aimed at assessing the value of Xpert MTB/RIF Ultra (Xpert-Ultra) in PTB on stool in adult in low HIV settings and Xpert-Ultra assay on stool sample harboring comparable sensitivity with Xpert MTB/RIF on respiratory tract specimens. Although the yield in stool samples by Xpert-Ultra is lower than RTS, it may be useful in detecting disease in presumptive TB patients who cannot expectorate sputum and are not open to BALF collection. In addition, Xpert-Ultra with a "trace call" on stool in adult was highly supportive of PTB.

In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis.

Background: Sudapyridine (WX-081) has exhibited equivalent efficacy than its counterpart parent drug bedaquiline (BDQ) but better safety profile against Mycobacterium tuberculosis (Mtb). Our study was aimed to evaluate in vitro activity of WX-081 against the clinical isolates of Mtb with different drug-resistance profiles and the intracellular bactericidal activity against the reference strain. Methods: The minimum inhibitory concentrations (MICs) of WX-081 and BDQ were tested against 114 Mtb clinical isolates. The intracellular activity of WX-081 and BDQ against the Mtb reference strain H37Rv in THP-1 cells was also evaluated in parallel. Results: The MICs for WX-081 of the enrolled isolates ranged from 0.0156 µg/mL to 1 µg/mL. The MIC50 and MIC90 of WX-081 were, respectively, 0.25 µg/mL and 0.5 µg/mL, with 95.6% of the enrolled strains having MICs ≤0.25 µg/mL. For a given strain, the MIC value of WX-081 was generally equivalent to or 2-fold than MIC of BDQ. The intracellular bacterial killing was acquired with the tested drug concentrations that were presumed attainable during clinical usage. Conclusion: WX-081 exhibited potent efficacy against the clinical isolates in vitro. The intracellular killing effect of sudapyridine against the reference strain supports its potential efficacy in treating TB patients.

In Vitro Activity of the Sudapyridine (WX-081) against Non-Tuberculous Mycobacteria Isolated in Beijing, China.

Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows an anti-tuberculosis activity but, unlike BDQ, did not prolong QT interval (QT) in animal model studies. This study evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM). Fifty reference strains of different mycobacterial species, and 132 NTM clinical isolates from four commonly isolated NTM species were recruited. The microplate alamarBlue assay was performed to determine the MIC of WX-081 and BDQ. Cytotoxicity assay was performed for both drugs using the THP-1 cells, and the minimum bactericidal concentrations (MBCs) of both drugs against the reference strains of five selected NTM species were also determined. All the tested reference strains had MICs lower than 0.5 µg/mL, with the majority having MICs far below 0.1 µg/mL for WX-081. The epidemiological cut-offs of WX-081 ranged from 0.0156 µg/mL to 0.25 µg/mL against commonly isolated NTM, and this value was comparable with that of BDQ. The MBC/MIC ratios suggest a bacteriostatic activity for both drugs against the five selected NTM species. Cytotoxicity assays indicated that THP-1 cells had nearly 100% viability when exposed to WX-081 for 24 h below 4 µg/mL, 200- to 300-fold the MICs of Mycobacterium intracellulare, Mycobacterium avium, and Mycobacterium kansasii. WX-081 has a strong antimicrobial activity against different NTM species with low cytotoxicity and therefore has the potential to be used for treating NTM infections. IMPORTANCE Due to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. Over 200 species or subspecies of NTM have been reported, whereas pulmonary diseases in humans are caused mainly by M. avium complex (MAC), M. kansasii, and M. abscessus. Treatment of NTM infection is often challenging as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant-tuberculosis (MDR-TB) may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the antituberculosis efficacy but eliminate the severe side effect of BDQ. This study initially evaluated the antimicrobial activity of this novel drug against non-tuberculous mycobacteria (NTM).

Bone Penetration of Cycloserine in Osteoarticular Tuberculosis Patients of China.

The cycloserine concentrations in plasma and bone that were collected during operations on 28 osteoarticular tuberculosis (TB) patients treated daily with a 500-mg cycloserine-containing regimen were determined. The median concentrations in plasma and bone were 16.29 µg/mL (interquartile range [IQR], 6.47 µg/mL) and 24.33 µg/g (IQR, 14.68 µg/g), respectively. The median bone/plasma penetration ratio was 0.76 (range, 0.33 to 1.98). Cycloserine could effectively penetrate bone and acquire concentrations comparable to those in plasma, which favors its usage in osteoarticular TB treatment.