Multicenter evaluation of the biochip assay for rapid detection of mycobacterial isolates in smear-positive specimens

Objectives: The objective of this study was to conduct a multicentre evaluation of the performance of the biochip assay in the rapid identification of mycobacteria in smear-positive sputum specimens. Methods: A total of 1751 sputum specimens were obtained from 7 cities in Zhejiang, China. All of the specimens were used for the discrimination of Mycobacterium species using the biochip assay, and the results were compared to the golden standard method of culture, hsp65, 16S rRNA and rpoB sequence analysis. Results: In the 1751 sputum specimens, 1685 samples were cultured successfully; among these samples, 1361 were Mycobacterium tuberculosis, 323 were NTM and 1 was Nocadia farcinica. Of the 323 NTM, most of them were Mycobacterium intracellulare(52.5%) followed by Mycobacterium abscessus (20.7%), Mycobacterium avium (11.7%), Mycobacterium kansasii (9.6%) and Mycobacterium fortuitum (1.9%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the biochip assay to differentiate TB and NTM from AFB positive specimens were 99.8%, 99.7%, 99.9%, 99.1%, 98.8%, 1, 1, and 99.7%, respectively. The concordance between the biochip assay and mycobacterial culture for the identification of NTM species was 95.4%. Conclusions: The biochip assay is a reliable tool for the rapid identification of most mycobacteria in clinical sputum specimens. This assay can be helpful for physicians in the early diagnosis and treatment of mycobacterium infections. Keywords: Mycobacterium tuberculosis, Nontuberculous mycobacteria, Species identification, Molecular diagnosis, Biochip Assay, Sputu

Clinical characteristics and antimicrobial susceptibility profiles of Mycobacterium abscessus and Mycobacterium massiliense pulmonary infection

Objectives: Mycobacterium abscessus complex (MABC) is the most common rapidly growing Mycobacterium species in structural pulmonary diseases and can be life-threatening. This study aimed to assess the clinical characteristics and drug-susceptibility statuses of different M. abscessus (MAB) subspecies in the Zhejiang Province. Methods: DNA sequencing was used to differentiate clinical MABC subspecies isolates. The Clinical and Laboratory Standards Institute guidelines were used to determine in vitro susceptibility of imipenem-relebactam (IMP-REL), omadacycline, and other conventional antibiotics. Patient clinical characteristics were collected and analysed. Results: In total, 139 M. abscessus, 39 Mycobacterium massiliense, and 1 Mycobacterium bolletii isolates were collected, accounting for 77.7%, 21.8%, and 0.5% of the MABC isolates, respectively. Patients with M. abscessus pulmonary disease (M.ab-PD) had higher proportions of older adults, tuberculosis history, chronic pulmonary disease, and malignancy than those with M. massiliense pulmonary disease (M.ma-PD). Patients with M.ab-PD had higher rates of bilateral middle- and lower-lobe involvement than patients with M.ma-PD. Both subspecies showed high resistance rates to doxycycline and moxifloxacin, and clarithromycin-induced resistance was more common in M.ab than in M.ma. IMP-REL resulted in a twofold reduction in the minimum inhibitory concentration (MIC) value compared with imipenem alone among MAB; furthermore, the MIC was lower in M.ab than in M.ma. Omadacycline and tigecycline had comparable in vitro susceptibility, and the MIC showed no statistically significant difference between M.ab and M.ma. Conclusions: M.ab is the most prevalent MABC subspecies in the Zhejiang Province. Patients with M.ab-PD have complex underlying diseases and broader lobar lesions. IMP-REL and omadacycline are promising antibiotics for MABC infection treatment

Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation

ABSTRACTWith the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen

Randomized control study of the use of faropenem for treating patients with pulmonary tuberculosis

ABSTRACT: Objectives: Faropenem has antituberculosis activity in vitro but its utility in treating patients with tuberculosis (TB) is unclear. Methods: We conducted an open-label, randomized trial in China, involving newly diagnosed, drug-susceptible pulmonary TB. The control group was treated with the standard 6-month regimen. The experimental group replaced ethambutol with faropenem for 2 months. The primary outcome was the treatment success rate after 6 months of treatment. Noninferiority was confirmed if the lower limit of a 95% one-sided confidence interval (CI) of the difference was greater than −10%. Results: A total of 227 patients eligible for the study were enrolled in the trial group and the control group in a ratio of 1:1. Baseline characteristics of participants were similar in both groups. In the modified intention-to-treat population, 88.18% of patients in the faropenem group achieved treatment success, and 85.98% of those in the control group were successfully treated, with a difference of 2.2% (95% CI, −6.73-11.13). In the per-protocol population, treatment success was 96.04% in the faropenem group and 95.83% in the control group, with a difference of 2.1% (95% CI, −5.31-5.72). The faropenem group showed noninferiority to the control group in the 6-month treatment success rates. The faropenem group had significantly fewer adverse events (P <0.01). Conclusions: Our study proved that oral faropenem regimen can be used for the treatment of TB, with fewer adverse events. (Chinese Clinical Trial Registry, ChiCTR1800015959)

Broad-Spectrum Antimicrobial Supramolecular Assemblies with Distinctive Size and Shape

With the increased prevalence of antibiotic-resistant infections, there is an urgent need for innovative antimicrobial treatments. One such area being actively explored is the use of self-assembling cationic polymers. This relatively new class of materials was inspired by biologically pervasive cationic host defense peptides. The antimicrobial action of both the synthetic polymers and naturally occurring peptides is believed to be complemented by their three-dimensional structure. In an effort to evaluate shape effects on antimicrobial materials, triblock polymers were polymerized from an assembly directing terephthalamide-bisurea core. Simple changes to this core, such as the addition of a methylene spacer, served to direct self-assembly into distinct morphologiesspheres and rods. Computational modeling also demonstrated how subtle core changes could directly alter urea stacking motifs manifesting in unique multidirectional hydrogen-bond networks despite the vast majority of material consisting of poly(lactide) (interior block) and cationic polycarbonates (exterior block). Upon testing the spherical and rod-like morphologies for antimicrobial properties, it was found that both possessed broad-spectrum activity (Gram-negative and Gram-positive bacteria as well as fungi) with minimal hemolysis, although only the rod-like assemblies were effective against Candida albicans