New All-Oral Short-term Regimen for Multidrug-Resistant Tuberculosis: A Semi-randomized Controlled Trial Conducted in China.

Background: This study aimed to evaluate the efficacy and safety of an all-oral short-term regimen for treating multidrug-resistant tuberculosis (MDR-TB).

Methods: In this semirandomized, controlled, multicenter clinical study, patients with MDR-TB who were sensitive to fluoroquinolones were assigned to treatment groups at enrollment. Patients were assigned to group C (4-6 months: bedaquiline + linezolid + clofazimine + moxifloxacin + cycloserine; 5 months: clofazimine + moxifloxacin + cycloserine) unless this protocol was unsuitable or unacceptable, in which case they were randomly assigned to group A (4-6 months: isoniazid + ethambutol + pyrazinamide + protionamide + amikacin + clofazimine + moxifloxacin; 5 months: ethambutol + pyrazinamide + clofazimine + moxifloxacin) or group B (4-6 months: isoniazid + ethambutol + pyrazinamide + protionamide + linezolid + clofazimine + moxifloxacin; 5 months: ethambutol + pyrazinamide + clofazimine + moxifloxacin).

In vitro monitoring of drug resistance emergence during stepwise induction of bedaquiline and clofazimine, alone and in combination: a phenotypic and genotypic analysis.

Objectives: The co-resistance between bedaquiline and clofazimine raises significant concerns, as they are commonly co-administered as core drugs in drug-resistant TB regimens. The present study aimed to monitor drug resistance-associated gene mutations and the phenotypic change in Mycobacterium tuberculosis (Mtb) under a stepwise drug resistance induction in vitro using bedaquiline, clofazimine or combined drugs.

Methods: Drug-resistant Mtb strains were gradually induced in vitro on a drug-containing solid medium with a 2-fold increasing concentration of bedaquiline, clofazimine and their combination.

Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

Background: Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission.

Methods: Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases.

Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

Purpose: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays.

Methods: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared.

Artificial intelligence-driven computer aided diagnosis system provides similar diagnosis value compared with doctors' evaluation in lung cancer screening.

Objective: To evaluate the consistency between doctors and artificial intelligence (AI) software in analysing and diagnosing pulmonary nodules, and assess whether the characteristics of pulmonary nodules derived from the two methods are consistent for the interpretation of carcinomatous nodules.

Materials And Methods: This retrospective study analysed participants aged 40-74 in the local area from 2011 to 2013. Pulmonary nodules were examined radiologically using a low-dose chest CT scan, evaluated by an expert panel of doctors in radiology, oncology, and thoracic departments, as well as a computer-aided diagnostic(CAD) system based on the three-dimensional(3D) convolutional neural network (CNN) with DenseNet architecture(InferRead CT Lung, IRCL).

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

Objective: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB).

Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto).

Efflux pump effects on levofloxacin resistance in .

) inherently displays resistance to most antibiotics, with the underlying drug resistance mechanisms remaining largely unexplored. Efflux pump is believed to play an important role in mediating drug resistance. The current study examined the potential of efflux pump inhibitors to reverse levofloxacin (LFX) resistance in .

Comparison of the antibacterial activity of ofloxacin, levofloxacin, moxifloxacin, sitafloxacin, finafloxacin, and delafloxacin against strains isolated in China.

Objective: The resistance of () to currently available fluoroquinolones (FQs), namely ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), renders the treatment of TB infections less successful. In this study, we aimed to evaluate the susceptibility and intracellular killing assay of to next-generation FQs and determine the correlation of FQs resistance and newly detected mutations in by molecular docking.

Methods: Antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations (MICs) of six FQs, including currently available FQs (OFX, LFX, and MFX) and next-generation FQs, i.

Clinical Utility of Contezolid-Containing Regimens in 25 Cases of Linezolid-Intolerable Tuberculosis Patients.

Objective: Linezolid is increasingly used in the treatment of multidrug-resistant (MDR) (TB) with good efficacy; however, its clinical use is limited by intolerable adverse events (AEs). This usually results in dose adjustment or even discontinuation. Contezolid is a new oxazolidinone antibiotic with in vitro antibacterial activity against MDR TB equivalent to linezolid, but its safety and efficacy in MDB TB treatment has not been established.

Antibacterial activity of the novel compound Sudapyridine (WX-081) against .

Objective: This study aimed to investigate sudapyridine (WX-081) antibacterial activity against and its effect on bacterial growth and host survival using a zebrafish model of infection.

Methods: WX-081 antibacterial activity was assessed based on growth inhibition of standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of growth were assessed after fluorescently labelled bacilli and drugs were injected into zebrafish.

Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) against .

Objective: To evaluate contezolid (MRX-I) antibacterial activity against and and to assess whether MRX-I treatment can prolong survival of infected zebrafish.

Methods: MRX-I inhibitory activity against was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled . Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on growth inhibition using one-way ANOVA.

Bedaquiline resistance pattern in clofazimine-resistant clinical isolates of tuberculosis patients.

Objectives: Bedaquiline (BDQ) is a potent drug for treating drug-resistant tuberculosis (TB). Here, we analysed the resistance profiles of BDQ in CFZ-resistant clinical isolates and investigated the clinical risk factors of BDQ and CFZ cross/co-resistance.

Methods: The AlarmarBlue microplate assay was performed to determine the minimum inhibitory concentration (MIC) of the CFZ-resistant Mycobacterium tuberculosis (MTB) clinical isolates to CFZ and BDQ.

Diagnostic value of a nanopore sequencing assay of bronchoalveolar lavage fluid in pulmonary tuberculosis.

Background: To determine the diagnostic accuracy of a nanopore sequencing assay of PCR products from a M. tuberculosis complex-specific region for testing of bronchoalveolar lavage fluid (BALF) samples or sputum samples from suspected pulmonary tuberculosis (PTB) patients and compare the results to results obtained for MGIT and Xpert assays.

Methods: Cases with suspected PTB (n = 55) were diagnosed from January 2019 to December 2021 based on results of nanopore sequencing, MGIT culture, and Xpert MTB/RIF testing of BALF and sputum samples collected during hospitalization.

A study of risk factors for tuberculous meningitis among patients with tuberculosis in China: An analysis of data between 2012 and 2019.

Purpose: The present study aimed to explore the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB).

Methods: This retrospective study was conducted on patients with TB who were hospitalized in Beijing Chest Hospital between January 2012 and December 2019. Demographic and clinical data of patients with TB were extracted from electronic medical records using a standardized data collection system.

High accuracy of recombinant fusion protein early secretory antigenic target protein 6-culture filtrate protein 10 skin test for the detection of tuberculosis infection: a phase III, multi-centered, double-blind, hospital-based, randomized controlled trial.

Objectives: To verify the diagnostic utility of recombinant fusion protein ESAT6-CPF10 (EC), a novel skin test reagent to detect Mycobacterium tuberculosis infection.

Methods: A multi-centered, double-blind, randomized controlled trial was conducted from December 17, 2015, to March 2, 2018. Participants involved in this study included those with active tuberculosis (TB), suspected pulmonary TB, or non-TB pulmonary disease.

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.

Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: A multicenter, randomized, phase II trial.

Background And Aims: Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI.

Methods: This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial.

Linezolid Pharmacokinetics/Pharmacodynamics-Based Optimal Dosing for Multidrug-Resistant Tuberculosis.

Objectives: Linezolid can significantly impact drug-resistant tuberculosis (DR-TB) patient outcomes. However, the long-term use of this drug for TB treatment has been limited by adverse reactions and uncertainty regarding optimal dosage regimens for balancing drug efficacy and safety across different populations. This study attempted to find the optimal dosing regimen of linezolid in different populations.

Adjunctive interleukin-2 for the treatment of drug-susceptible tuberculosis: a randomized control trial in China.

Purpose: Evaluation of the efficacy and safety of IL-2 in the treatment of drug-susceptible tuberculosis.

Methods: First, the cases of diagnosed drug-susceptible tuberculosis were randomized into two groups-the control group that received the background regimen of isoniazid, rifampin, pyrazinamide, and ethambutol, and the experimental group that received the background regimen plus IL-2. The efficacy and safety evaluations were performed throughout the therapy process as well as 12 months after the treatment completion.

Xpert MTB/RIF Ultra enhanced tuberculous pleurisy diagnosis for patients with unexplained exudative pleural effusion who underwent a pleural biopsy via thoracoscopy: A prospective cohort study.

Introduction: To evaluate the performance of Xpert MTB/RIF Ultra (Xpert-Ultra) in testing pleural tissue and fluid collected by medical thoracoscopy among patients with unexplained exudative pleural effusion.

Methods: Patients with an undiagnosed exudative pleural effusion were prospectively and consecutively recruited. Pleural tissue and fluid were collected by medical thoracoscopy and subjected to culture, Xpert MTB/RIF (Xpert) and Xpert-Ultra assays.

Carbonyl Cyanide 3-Chlorophenylhydrazone (CCCP) Exhibits Direct Antibacterial Activity Against .

Objective: Treatment choices for () infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against infection are urgently needed. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a member of the lipophilic weak acid class, is known as an efflux pump inhibitor for .

Bipolar Distribution of Minimum Inhibitory Concentration of Q203 Across Mycobacterial Species.

In this study, we conducted an experimental study to evaluate susceptibility of Q203 against , as well as the major pathogenic nontuberculous mycobacterial species. A total of 344 nonduplicate mycobacterium isolates were randomly selected for susceptibility testing. Overall, Q203 exhibited excellent activity against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates, whereas it showed high minimum inhibitory concentration (MIC) values for all nontuberculous mycobacteria (NTM) isolates tested.