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Objective·To investigate the impact of complications on the prognosis and lung injury of patients with tuberculosis..Methods·A retrospective cohort study was used for analysis, to select a total of 450 smear-positive tuberculosis (TB) patients, 323 males (71.8%) and 127 females (28.2%), from January to December 2018 at Shanghai Pulmonary Hospital, Tongji University School of Medicine, which were divided into non-complication group and complication group (diabetes, hypertension, liver diseases, kidney diseases and gallbladder diseases). Overall treatment outcomes and lung injuries in TB patients with and without complications were analyzed by using χ2 test. Stratified analysis of the impact of each comorbidity on the prognosis and lung injury of TB patients was performed. Kaplan-Meier analysis was used to analyze the temporal correlation between complications and tuberculosis prognosis.Results·Four hundred and fifty patients with a median age of 33 years were included, 173 of whom had complications: diabetes in 49 cases, hypertension in 23 cases, liver diseases in 83 cases, kidney diseases in 35 cases, and gallbladder diseases in 17 cases. The cure rate of TB patients without complications was 80.5%, which was significantly higher than that of the group with complications (P

Carbapenemase-producing Enterobacterales (CPE) have emerged as important nosocomial pathogens and are a global public health concern because of the high prevalence of CRE infection and its associated mortality rate. Currently, [...]

Background: Daptomycin non-susceptible Staphylococcus aureus (DNS) strains pose a serious clinical threat, yet their characteristics remain poorly understood. Methods: DNS derivatives were generated by exposing S. aureus strains to subinhibitory concentrations of daptomycin. Competition experiment and growth kinetics experiment were used to observe the growth of bacteria. Galleria mellonella larvae and mouse skin abscess models were used to observe the virulence of bacteria. Transmission electron microscopy (TEM), cytochrome C experiment and biofilm formation experiment were used to observe the drug resistance phenotype. And homologous recombination was used to study the role of mutations. Results: Phenotypic profiling of DNS strains revealed impaired growth, increased cell wall thickness, enhanced biofilm formation, reduced negative surface charge, and attenuated virulence compared to their wild-type strains. Whole genome sequencing identified mutations in mprF , cls2 , and saeR in DNS strains. Allelic replacement experiments validated the roles of MprF L341F and Cls2 F60S substitutions in augmenting daptomycin non-susceptibility in Newman. Deletion of saeR in the NewmanMprFL341F strain and complementation of saeR in the Newman-DNS strain did not directly alter daptomycin susceptibility. However, the deletion of saeR was found to enhance competitive fitness under daptomycin pressure. Conclusion: This work validates adaptive laboratory evolution (ALE) for modeling clinical DNS strains and uncovers contributions of mprF , cls2 , and saeR mutations to the adaptation and resistance mechanisms of S. aureus against daptomycin. These findings enrich our understanding of how S. aureus acquired resistance to daptomycin, thus paving the way for the development of more effective treatment strategies and offering potential molecular markers for resistance surveillance. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the emergence and characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that demonstrate resistance to multiple antibiotics, including aminoglycosides and tigecycline, in a Chinese hospital. Methods: A group of ten CRKP strains were collected from the nine patients in a Chinese hospital. Antimicrobial Susceptibility Testing (AST) and phenotypic inhibition assays precisely assess bacterial antibiotic resistance. Real-time quantitative PCR (RT-qPCR) was used to analyze the mRNA levels of efflux pump genes (acrA/acrB and oqxA/oqxB) and the regulatory gene (ramA). The core-genome tree and PFGE patterns were analyzed to assess the clonal and horizontal transfer expansion of the strains. Whole-genome sequencing was performed on a clinical isolate of K. pneumoniae named Kpn20 to identify key resistance genes and antimicrobial resistance islands (ARI). Results: The CRKP strains showed high resistance to carbapenems, aminoglycosides (CLSI, 2024), and tigecycline (EUCAST, 2024). The mRNA expression levels of efflux pump genes and regulatory genes were detected by RT-qPCR. All 10 isolates had significant differences compared to the control group of ATCC13883. The core-genome tree and PFGE patterns revealed five clusters, indicating clonal and horizontal transfer expansion. Three key resistance genes (blaoxa-232, blaCTX-M-15, and rmtF) were observed in the K. pneumoniae clinical isolate Kpn20. Mobile antibiotic resistance islands were identified containing blaCTX-M-15 and rmtF, with multiple insertion sequences and transposons present. The coexistence of blaoxa-232 and rmtF in a high-risk K. pneumoniae strain was reported. Conjugation assay was utilized to investigate the transferability of blaoxa-232-encoding plasmids horizontally. Conclusion: The study highlights the emergence of ST15-KL112 high-risk CRKP strains with multidrug resistance, including to aminoglycosides and tigecycline. The presence of mobile ARI and clonal and horizontal transfer expansion of strains indicate the threat of transmission of these strains. Future research is needed to assess the prevalence of such isolates and develop effective control measures. [ABSTRACT FROM AUTHOR]

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β-lactam/β-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae. Methods: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability. Results: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of blaKPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants. Discussion: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying blaKPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible. [ABSTRACT FROM AUTHOR]

Suppressing shock-induced flow separation has been a long-standing problem in the design of supersonic vehicles. To reduce the structural and design complexity of control devices, a passive control technique based on micro-serrations is proposed and its controlling effects are preliminarily investigated under test conditions in which the Mach number is 2.5 and the ramp creating an incident shock is 15 deg. Meanwhile, a vorticity-based criterion for assessing separation scales is developed to resolve the inapplicability of the zero skin friction criterion caused by wall unevenness. The simulations demonstrate that the height of the first stair significantly influences the separation length. Generally, the separation length is shorter at higher stairs, but when the height is greater than half of the thickness of the incoming boundary layer, the corresponding separation point moves upstream. A stair with a height of only 0.4 times the thickness of the boundary layer reduces the separation length by 2.69%. Further parametric analysis reveals that while the remaining serrations have limited effects on the flow separation, an optimization of their shape (depth and width) can create more favorable spanwise vortices and offer a modest improvement of the overall controlling performance. Compared to the plate case, a 9.13% reduction in the separation length can be achieved using a slightly serrated design in which the leading stair is 0.1 high and the subsequent serrations are 0.2 deep and 0.05 wide (nondimensionalized, with the thickness of the incoming boundary layer). Meanwhile, the micro-serration structure even brings less drag. Considering the minor modification to the structure, the proposed method has the potential for use in conjunction with other techniques to exert enhanced control on separations. [ABSTRACT FROM AUTHOR]