Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002–2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.

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Carbapenem-resistant (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible, ,, or infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by (73.9%), followed by (16.6%) and (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against than against (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among and The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.

h i g h l i g h t sWe propose a novel hybrid model to forecast PM 2.5 pollution.Using trajectory based geographic parameter as an extra input to ANN model. Applying prediction strategy at different scales and then sum them up. The model is capable to predict the high peaks of PM 2.5 concentrations. a b s t r a c tIn the paper a novel hybrid model combining air mass trajectory analysis and wavelet transformation to improve the artificial neural network (ANN) forecast accuracy of daily average concentrations of PM 2.5 two days in advance is presented. The model was developed from 13 different air pollution monitoring stations in Beijing, Tianjin, and Hebei province (Jing-Jin-Ji area). The air mass trajectory was used to recognize distinct corridors for transport of "dirty" air and "clean" air to selected stations. With each corridor, a triangular station net was constructed based on air mass trajectories and the distances between neighboring sites. Wind speed and direction were also considered as parameters in calculating this trajectory based air pollution indicator value. Moreover, the original time series of PM 2.5 concentration was decomposed by wavelet transformation into a few sub-series with lower variability. The prediction strategy applied to each of them and then summed up the individual prediction results. Daily meteorological forecast variables as well as the respective pollutant predictors were used as input to a multi-layer perceptron (MLP) type of back-propagation neural network. The experimental verification of the proposed model was conducted over a period of more than one year (between September 2013 and October 2014). It is found that the trajectory based geographic model and wavelet transformation can be effective tools to improve the PM 2.5 forecasting accuracy. The root mean squared error (RMSE) of the hybrid model can be reduced, on the average, by up to 40 percent. Particularly, the high PM 2.5 days are almost anticipated by using wavelet decomposition and the detection rate (DR) for a given alert threshold of hybrid model can reach 90% on average. This approach shows the potential to be applied in other countries' air quality forecasting systems.

Objectives Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) have been increasingly reported in China. Here, a multicentre, longitudinal surveillance study on CR-hvKP is described. Methods We retrospectively investigated carbapenem-resistant K. pneumoniae (CRKP) in 56 centres across China during 2015–17 and screened the virulence genes (iucA, iroN, rmpA and rmpA2) for the presence of virulence plasmids. Hypermucoviscosity, serum killing and Galleria mellonella lethality experiments were conducted to identify CR-hvKP among strains with all four virulence genes. Capsule typing, fitness and plasmid features of CR-hvKP were also investigated. Results A total of 1052 CRKP were collected. Among these, 34.2% (360/1052) carried virulence genes and 72 of them had all four of the virulence genes tested. Fifty-five (76.4%) were considered to be CR-hvKP using the G. mellonella infection model, with KPC-2-producing K64-ST11 being the most common type (80%, 44/55). Prevalence of CR-hvKP differed greatly between regions, with the highest in Henan (25.4%, 17/67) and Shandong (25.8%, 25/97). A significant increase in CR-hvKP among KPC-2-producing ST11 strains was observed, from 2.1% (3/141) in 2015 to 7.0% (23/329) in 2017 (P=0.045). Alarmingly, compared with classic CRKP, no difference in growth was found among CR-hvKP (P=0.7028), suggesting a potential risk for dissemination. The hybrid virulence and resistance-encoding plasmid evolved from pLVPK and the resistance plasmid harbouring blaKPC-2, indicating evolution existed between the hypervirulence and hyper-resistance plasmid. Conclusions CR-hvKP were more frequently detected than previously assumed, especially among KPC-2-producing ST11. Dissemination of hypervirulence could be extremely rapid due to limited fitness cost. Also, the evolution of resistance genes into hypervirulence plasmids was identified, presenting significant challenges for public health and infection control.