Arginine-Enhanced Antimicrobial Activity of Nanozymes against Gram-Negative Bacteria.

The continuous reduction of clinically available antibiotics has made it imperative to exploit more effective antimicrobial therapies, especially for difficult-to-treat Gram-negative pathogens. Herein, it is shown that the combination of an antimicrobial nanozyme with the clinically compatible basic amino acid L-arginine affords a potent treatment for infections with Gram-negative pathogens. In particular, the antimicrobial activity of the antimicrobial nanozyme is dramatically increased by ≈1000-fold after L-arginine stimulation.

Comparative Genomic Analysis of Hypervirulence Carbapenem-Resistant from Inpatients with Infection and Gut Colonization, China.

Background: The emergence and spread of hypervirulent carbapenem-resistant (hv-CRKP) is a potential epidemiological threat that needs to be monitored. However, the transmission and pathogenic characteristics of hv-CRKP in China remain unclear. We investigated the epidemiological characteristics of gut colonized hv-CRKP in a hospital in Guangdong Province, China.

Predominance of Escherichia-Shigella in Gut Microbiome and Its Potential Correlation with Elevated Level of Plasma Tumor Necrosis Factor Alpha in Patients with Tuberculous Meningitis.

Tuberculous meningitis (TBM), the most lethal and disabling form of tuberculosis (TB), may be related to gut microbiota composition, warranting further study. Here we systematically compared gut microbiota compositions and blood cytokine profiles of TBM patients, pulmonary TB patients, and healthy controls. Notably, the significant gut microbiota dysbiosis observed in TBM patients was associated with markedly high proportions of Escherichia-Shigella species as well as increased blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6).

A Peptidomic Approach to Identify Novel Antigen Biomarkers for the Diagnosis of Tuberculosis.

Background: Here, we conducted a peptidomic study in murine model to identify novel antigen biomarkers for the diagnosis of tuberculosis (TB) with improved performance.

Methods: Four recombinant proteins, including protein 32 (MPT32), protein 64 (MPT64), culture filtrate protein 10 (CFP10), and phosphate ABC transporter substrate-binding lipoprotein (PstS1) were expressed and intravenously injected into BALB/c mice. The serum were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

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.

In vitro Antimicrobial Activity Comparison of Linezolid, Tedizolid, Sutezolid and Delpazolid Against Slowly Growing Mycobacteria Isolated in Beijing, China.

Background: The antimicrobial activities of some new oxazolidinones against slowly growing mycobacteria (SGM) have never been well evaluated.

Methods: We evaluate the in vitro susceptibility of 20 reference strains and 157 clinical isolates, pertaining different SGM species, against four oxazolidinones, ie, delpazolid, sutezolid, tedizolid and linezolid. In addition, the association of linezolid resistance and mutations in 23srRNA, were also tested.

Comparison of the in vitro activity of linezolid, tedizolid, sutezolid, and delpazolid against rapidly growing mycobacteria isolated in Beijing, China.

Background: The natural resistance of rapidly growing mycobacteria (RGM) to multiple antibiotics renders the treatment of the infections caused less successful. The objective of this study was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species.

Methods: The microplate alamarBlue assay was performed to identify the minimum inhibitory concentrations (MICs) of four oxazolidinones - delpazolid, sutezolid, tedizolid, and linezolid - for 32 reference strains and 115 clinical strains of different RGM species.

Bone penetration of linezolid in osteoarticular tuberculosis patients of China.

Background: Linezolid presents strong antimicrobial activity against multidrug-resistant (MDR) pulmonary tuberculosis (TB), but its application in osteoarticular tuberculosis treatment remains understudied. Our objective was to analyze the bone penetration efficiency of linezolid in osteoarticular TB patients.

Methods: Osteoarticular TB patients, treated with 600 mg q 24 h linezolid-containing regimens and undergoing surgery, were prospectively and consecutively enrolled.

Population Pharmacokinetic Analysis of Isoniazid among Pulmonary Tuberculosis Patients from China.

The blood concentration of isoniazid (INH) is evidently affected by polymorphisms in -acetyltransferase 2 (NAT2), an enzyme that is primarily responsible for the trimodal (i.e., fast, intermediate, and slow) INH elimination.

Susceptibility Testing of GSK656 against Species.

In this study, we aimed to assess the susceptibility to GSK656 among multiple mycobacterial species and to investigate the correlation between leucyl-tRNA synthetase (LeuRS) sequence variations and susceptibility to GSK656 among mycobacterial species. A total of 187 mycobacterial isolates, comprising 105 isolates and 82 nontuberculous mycobacteria (NTM) isolates, were randomly selected for the determination of susceptibility. For , 102 of 105 isolates had MICs of ≤0.

Penetration of linezolid into bone tissue 24 h after administration in patients with multidrug-resistant spinal tuberculosis.

Background: Linezolid has shown strong antimicrobial activity against multidrug-resistant (MDR)/rifampin-resistant strains of Mycobacterium tuberculosis. Linezolid achieves clinical efficacy mainly through area under the concentration time curve/minimum inhibitory concentration ratio in the infected lesion site. Previous studies mainly focused on the relationship between linezolid concentrations in the blood and infected bone tissue when the blood drug concentration reached the peak 2 h after administration.

Development and Clinical Validation of Multiple Cross Displacement Amplification Combined With Nanoparticles-Based Biosensor for Detection of : Preliminary Results.

Tuberculosis is still a major threat to global public health. Here, a novel diagnosis assay, termed as multiple cross displacement amplification combined with nanoparticle-based lateral flow biosensor (MCDA-LFB), was developed to simultaneously detect IS and IS of (MTB) in DNA extracted from reference strain H37Rv and clinical samples. The amplification can be finished within 30 min at a fixed temperature (67°C), thus the whole procedure, including rapid template preparation (15 min), isothermal reaction (30 min) and result reporting (2 min), can be completed within 50 min.

Para-aminosalicylic acid increases the susceptibility to isoniazid in clinical isolates of .

The purpose of this work was to assess the activity of para-aminosalicylic acid (PAS) in combination with isoniazid (INH) against clinical isolates of (MTB). A total of 72 MTB isolates with differential in vitro drug susceptibilities were included in this study, comprising 24 pan-susceptible, 24 MDR-TB, and 24 extensively drug-resistant (XDR) isolates. A microplate alamarBlue assay was performed to identify the minimal inhibitory concentrations (MICs) of MTB isolates.

Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis.

Delamanid exhibited greater in vitro potency than pretomanid against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates. The pretomanid minimum inhibitory concentration (MIC) values of four MDR-TB isolates were found to be resistant to delamanid ranging from 0.031 to 0.

Activity of PBTZ169 against Multiple Mycobacterium Species.

In this study, we demonstrate that PBTZ169 exhibits significant differences in activity against multiple species. The amino acid polymorphism at codon 387 of decaprenylphosphoryl-beta-d-ribose oxidase (DprE1) can be used as a surrogate marker for susceptibility to PBTZ169 in mycobacteria. In addition, the amino acid substitution at codon 154 in DprE1 may be associated with acquired resistance to PBTZ169 in the mutants.

Comparison of Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China.

Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant In this study, we compared the activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, , and genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates.