Co-occurrence of hypervirulence and KPC-2 carbapenem resistant phenotypes in a highly-transmissible ST11 clone of Klebsiella pneumoniae has elicited deep concerns from public health stand point. To address this puzzle, we conducted a large-scale epidemiological, clinical and genomic study of K. pneumonia ST11 clones with both hypervirulence and carbapenem resistance in two tertiary hospitals in Zhejiang province. Most of the patients (15/23) were diagnosed with exclusively carbapenem-resistant K . pneumoniae (CRKP) infections. Ten death cases were reported, some of which are due to the failure of antibiotic therapies. As a result, we identified one new rare sequence types (ST449) to KPC-2-producing CRKP, in addition to the dominant ST11. These clinical isolates of K. pneumoniae are multi-drug resistant and possess a number of virulence factors. Experimental infections of wax moth larvae revealed the presence of hypervirulence at varied level, suggesting the complexity in bacterial virulence factors. However, plasmid curing assays further suggested that the rmpA2 -virulence plasmid is associated with, but not sufficient for neither phenotypic hypermucoviscosity nor virulence of K . pneumoniae . Intriguingly, all the rmpA2 genes were found to be inactive due to genetic deletion. In total, we reported 21 complete plasmid sequences comprising 13 rmpA2 -positive virulence plasmids and 8 bla KPC-2 -harboring resistance plasmids. In addition to the prevalent pLVKP-like virulence plasmid variants (~178kb), we found an unexpected diversity among KPC-2-producing plasmids whose dominant form is IncFII-IncR type (~120kb), rather than the previously anticipated version of ~170kb. These findings provide an updated snapshot of convergence of hypervirulence and carbapenem resistance in ST11 K. pneumoniae.

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To evaluate the safety and efficacy of total percutaneous closure of the femoral artery access site after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with the Perclose ProGlide device.This retrospective observational study during an almost 2-year period included 21 patients who underwent VA-ECMO in whom the femoral artery puncture site was closed percutaneously with Perclose ProGlide devices. Technical success was defined as successful arterial closure of the common femoral artery, without the need for additional surgical or endovascular procedures. Access site complications were recorded at 24 hours and 30 days after arterial closure, such as major bleeding requiring transfusion or surgical intervention, minor bleeding, groin infection, pseudoaneurysm, and lymphocele.Technical success was achieved in 20 patients (95.2%). One patient required surgical repair for an access site pseudoaneurysm. Eighteen femoral arteries were closed with 2 devices each, while 3 patients required the use of a third device for femoral artery access site closure to achieve adequate hemostasis. No arterial thrombosis, arterial dissection, arterial stenosis, groin infection, or arteriovenous fistula occurred during the periprocedural period (within 24 hours of arterial closure) or during 30-day follow-up.Percutaneous closure with the Perclose ProGlide device is a feasible procedure for closing femoral arterial access sites after VA-ECMO, with a low incidence of access site complications.

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ObjectivesThere are many studies of acute kidney injury (AKI) diagnosis models lack of external validation and prospective validation. We constructed the models using three databases to predict severe AKI within 48 hours in intensive care unit (ICU) patients.DesignA retrospective and prospective cohort study.SettingWe studied critically ill patients in our database (SHZJU-ICU) and two other public databases, the Medical Information Mart for Intensive Care (MIMIC) and AmsterdamUMC databases, including basic demographics, vital signs and laboratory results. We predicted the diagnosis of severe AKI in patients in the next 48 hours using machine-learning algorithms with the three databases. Then, we carried out real-time severe AKI prediction in the prospective validation study at our centre for 1 year.ParticipantsAll patients included in three databases with uniform exclusion criteria.Primary and secondary outcome measuresEffect evaluation index of prediction models.ResultsWe included 58 492 patients, and a total of 5257 (9.0%) patients met the definition of severe AKI. In the internal validation of the SHZJU-ICU and MIMIC databases, the best area under the receiver operating characteristic curve (AUROC) of the model was 0.86. The external validation results by AmsterdamUMC database were also satisfactory, with the best AUROC of 0.86. A total of 2532 patients were admitted to the centre for prospective validation; 358 positive results were predicted and 344 patients were diagnosed with severe AKI, with the best sensitivity of 0.72, the specificity of 0.80 and the AUROC of 0.84.ConclusionThe prediction model of severe AKI exhibits promises as a clinical application based on dynamic vital signs and laboratory results of multicentre databases with prospective and external validation.

Purpose Ceftazidime/avibactam (CAZ/AVI) monotherapy and polymyxin B-based combination therapy are currently two treatment options for patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection; however, few studies have contrasted the relative efficacy of the two antibiotic regimens. The purpose of this study was to compare the effectiveness of CAZ/AVI and polymyxin B against CRPA infection and analyze the independent predictors of 30-day mortality or survival. Patients and Methods This single-center retrospective observational study included patients with CRPA infection treated with CAZ/AVI or polymyxin B between January 2018 and December 2020. The primary outcomes were the 14-day and 30-day mortality. The secondary outcomes were in-hospital mortality and bacterial clearance. Baseline characteristics and outcomes were compared between the two groups, and COX regression analysis was used to identify predictors of 30-day mortality. Results A total of 136 patients with CRPA infection were enrolled, including 51 patients in the CAZ/AVI group and 85 patients in the polymyxin B group. The 14-day mortality (5.9% vs 27.1%, p=0.002), 30-day mortality (13.7% vs 47.1%, p<0.001) and in-hospital mortality (29.4% vs 60.0%, p=0.001) in the CAZ/AVI group were significantly lower than the polymyxin B group. The bacterial clearance rate (45.1% vs 12.9%, p<0.001) in the CAZ/AVI group were higher than in the polymyxin B group. After adjustment by propensity score matching, the CAV/AVI group still had lower 30-day mortality (14.3% vs 42.9%, p=0.018) and higher bacterial clearance rate (42.9% vs 14.3%, p=0.018) than the polymyxin B group. The multivariate COX analysis showed that the age was identified as independent predictor of 30-day mortality while CAZ/AVI therapy and central venous catheterization emerged as independent predictors of 30-day survival. Conclusion CAZ/AVI therapy was superior to polymyxin B therapy for patients with CRPA infection, and provided significant survival benefits, but further larger studies were needed to substantiate our findings.

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