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The global proliferation of carbapenemase-producing bacteria (CPB) has garnered significant attention worldwide. Early diagnosis of CPB and accurate identification of carbapenemases are crucial for preventing the spread of CPB and ensuring targeted antibiotic therapy. Therefore, efficient and accurate identification of carbapenemases is paramount in clinically treating diseases associated with CPB. In this study, 58 CPB strains were collected and detected using the DNA endonuclease-targeted CRISPR trans reporter (DETECTR) method, a rapid detection platform based on CRISPR-Cas12a gene editing and isothermal amplification. Additionally, four conventional methods (the APB/EDTA method, PCR, NG-test Carba 5, and GeneXpert Carba-R) were employed and compared against whole genome sequencing (WGS) results, considered the gold standard, to evaluate their efficacy in detecting carbapenemases. Detection by the APB/EDTA method revealed that 29 strains were positive for Class A serine endopeptidases, while 29 strains were positive for Class B metalloenzymes. The classification of these zymotypes was consistent with the sequencing result. All target carbapenemases for KPC were identified with 100% sensitivity using NG-test Carba 5, PCR, DETECTR, and GeneXpert Carba-R. In the case of NDM, both Xpert Carba-R and DETECTR showed a sensitivity of 100%. In contrast, NG-test Carba 5 and PCR had a slightly lower sensitivity of 96.7%, each missing one target carbapenemase. n this study, the APB/EDTA method is capable of identifying the zymotype classification but not the specific resistant genes, while Xpert Carba-R and DETECTR are able to detect all target carbapenemases.

Whooping cough (pertussis) is a contagious respiratory illness caused by Bordetella pertussis. The introduction of the whole-cell vaccine (WCV) successfully decreased the incidence of pertussis. Although vaccination has been successful, [...]

ObjectivesLevofloxacin is widely used because of its broad-spectrum antimicrobial activity and convenient dosing schedule. However, the relevance of its use in children remains to be investigated. The purpose of this study is to investigate the efficacy and safety of levofloxacin use in children with severe infections.MethodsWe conducted a retrospective observational study of patients

As one of the most induced genes in activated macrophages, immune-responsive gene 1 (IRG1) encodes a mitochondrial metabolic enzyme catalysing the production of itaconic acid (ITA). Although ITA has an anti-inflammatory property, the underlying mechanisms are not fully understood. Here we show that ITA is a potent inhibitor of the TET-family DNA dioxygenases. ITA binds to the same site on TET2 as the co-substrate α-ketoglutarate, inhibiting TET2 catalytic activity. Lipopolysaccharide treatment, which induces Irg1 expression and ITA accumulation, inhibits Tet activity in macrophages. Transcriptome analysis reveals that TET2 is a major target of ITA in suppressing lipopolysaccharide-induced genes, including those regulated by the NF-κB and STAT signalling pathways. In vivo, ITA decreases the levels of 5-hydroxymethylcytosine, reduces lipopolysaccharide-induced acute pulmonary oedema as well as lung and liver injury, and protects mice against lethal endotoxaemia, depending on the catalytic activity of Tet2. Our study thus identifies ITA as an immune modulatory metabolite that selectively inhibits TET enzymes to dampen the inflammatory responses.

Two independent experiments were performed with three groups each (sepsis control, sepsis, and sepsis with apoE23 treatment) to investigate the anti-inflammatory effect of apolipoprotein 23 (apoE23) in a mouse model of sepsis induced by S. typhimurium. Survival rates; plasma level variations in tumor necrosis factor (TNF)-α, interleukin (IL)-6, and lipopolysaccharide (LPS); S. typhimurium colony-forming units in the spleen tissue; and mRNA and protein expression levels of low-density lipoprotein receptor (LDLR), LDLR-related protein (LRP), syndecan-1, and scavenger receptor B1 were evaluated in the livers of mice from the three groups. Results found that the survival rate of septic mice treated with apoE23 was 100% within 48 h, while it was only 40% in septic mice without apoE23 treatment (P < 0.001). The plasma LPS, TNF-α, and IL-6 levels and the S. typhimurium load in mice in the apoE23-treated group were significantly lower than those in septic mice (P < 0.05). Moreover, apoE23 restored the downregulated expression of LDLR and LRP in the liver tissue of septic mice. So apoE23 exhibits an anti-inflammatory effect in the mouse model of S. typhimurium-induced sepsis. Further studies are required to understand the mechanisms underlying the anti-inflammatory effects of apoE23.

Background: Mechanical ventilation (MV) can cause diaphragmatic injury and ventilator induced diaphragmatic dysfunction (VIDD). Diaphragm ultrasonography (DU) is increasingly used to assess diaphragmatic anatomy, function and pathology of patients receiving MV in the pediatric intensive care unit (PICU). We report the poor contractile ability of diaphragm during ventilation of critically ill patients in our PICU and the association to prolonged length of MV and PICU stay. Methods: Patients who received MV within 24 h of admission to the PICU, expected to undergo continuous MV for more than 48 h and succeeded to extubate were included in the study. DU monitoring was performed daily after the initiation of MV until extubation. Diaphragm thickening fraction (DTF) measured by DU was used as an indicator of diaphragmatic contractile activity. Patients with bilateral DTF = 0% during DU assessment were allocated into the severe VIDD group (n = 26) and the rest were into non-severe VIDD group (n = 29). The association of severe VIDD with individual length of MV, hospitalization and PICU stay were analyzed. Results: With daily DU assessment, severe VIDD occurred on 2.9 ± 1.2 days after the initiation of MV, and lasted for 1.9 ± 1.7 days. Values of DTF of all patients recovered to > 10% before extubation. The severe VIDD group had a significantly longer duration (days) of MV [12.0 (8.0-19.3) vs. 5.0 (3.5–7.5), p < 0.001] and PICU stay (days) [30.5 (14.9–44.5) vs. 13.0 (7.0-24.5), p < 0.001]. The occurrence of severe VIDD, first day of severe VIDD and length of severe VIDD were significantly positively associated with the duration of MV and PICU stay. The occurrence of severe VIDD on the second and third days after initiation of MV significantly associated to longer PICU stay (days) [43.0 (9.0–70.0) vs. 13.0 (3.0–40.0), p = 0.009; 36.0 (17.0-208.0) vs. 13.0 (3.0–40.0), p = 0.005, respectively], and the length of MV (days) was significantly longer in those with severe VIDD on the third day after initiation of MV [16.5 (7.0–29.0) vs. 5.0 (2.0–22.0), p = 0.003]. Conclusions: Daily monitoring of diaphragmatic function with bedside ultrasonography after initiation of MV is necessary in critically ill patients in PICU and the influences and risk factors of severe VIDD need to be further studied. (355 words) [ABSTRACT FROM AUTHOR]