Search

Objective: Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, with a broad-spectrum antimicrobial activity, including against carbapenem-resistant gram-negative bacteria (CRGNB). However, the in vitro activity of eravacycline against CRGNB has not been well known in China. In this study, we analysed the antibacterial activity of eravacycline against CRGNB isolates in order to provide a theoretical basis for the clinical treatment. Methods: A total of 346 isolates of CRGNB were collected from two different tertiary care hospitals in Zhejiang, China. Carbapenem resistance genes of all isolates were detected by polymerase chain reaction. And we analysed the in vitro activity of eravacycline against CRGNB by antimicrobial susceptibility tests. In addition, the time-kill curves were generated to evaluate the antibacterial effect of tigecycline and eravacycline. Results: Four different types of carbapenem-resistant isolates were collected, including 50 Escherichia coli isolates, 160 Klebsiella pneumoniae isolates, 42 Enterobacter cloacae complex isolates, and 94 Acinetobacter baumannii isolates. The carbapenem resistance genes were identified in 346 isolates, including blaKPC-2 (48.0%), blaOXA-23 (27.2%), blaNDM-1 (23.1%), and blaNDM-16 (0.3%). The antimicrobial susceptibility testing results showed that the minimum inhibitory concentration (MIC) values of 346 isolates were within the sensitivity range (≤ 0.0625~16 mg/L) and that the MIC50 or MIC90 of eravacycline was generally approximately 2-fold lower than tigecycline. In addition, the time-kill curves showed that the bactericidal effect of eravacycline was stronger than that of tigecycline against four different types of isolates. Conclusion: Our research indicated that eravacycline had a good antibacterial effect on CRGNB, which could provide a theoretical basis for the clinical treatment of drug-resistant bacterial infections in the future. [ABSTRACT FROM AUTHOR]

• The ecosystem service (ES) and basic public service (BPS) trade-off is analyzed. • All the ESs and BPSs exhibited uneven distributions and temporal dynamic. • The overall ES-BPS trade-off in the study area showed a decrease trend. • Land urbanization aggregated the ES-BPS trade-off. • Population and economic urbanization mitigated the ES-BPS trade-off. With continuous urbanization and population growth, the socio-ecological demands of urban and rural residents have been increasingly intensive and diverse. Such demands need to be met by the ecosystem service (ES) provided by natural capital and the basic public service (BPS) provided by social capital together. However, the ES-BPS trade-off and the driving forces have not been fully revealed, which hinders the synergetic management of the ES and BPS. Therefore, we took the Middle and Lower Reach of the Yangtze River Economic Belt, one of the regions undergoing rapid urbanization in China, as the case study area, and explored the spatio-temporal ES-BPS trade-off and the urbanization driving forces during 2005 to 2019. We first quantified and mapped multiple ESs and BPSs, and then quantified the ES-BPS trade-off over the study period. Finally, we used geographically weighted regression model to reveal how three urbanization features (land, population, and economic urbanization) influenced the ES-BPS trade-off. We found that each ES and BPS, and the comprehensive ES and BPS (the overall capacity to provide multiple ESs and BPSs separately) all exhibited uneven spatial distributions. Results indicated that most eastern prefectures showed decreases in the comprehensive ES but great increases in the comprehensive BPS. Moreover, the ES-BPS trade-off in 2005 exhibited a pattern where the values were high in the south but low in the north, while such an interregional difference was weakened by 2019. From 2005 to 2019, the hotspots of ES-BPS trade-off changes appeared in Shanghai municipality and its surrounding areas, while the coldspots were mainly located in the southern part of Zhejiang Province. Although the influence degree of the three urbanization features on the ES-BPS trade-off spatially varied, population and economic urbanization continuously mitigated the ES-BPS trade-off but land urbanization exacerbated the trade-offs for the whole region. Overall, our study can contribute to the understanding of the ES-BPS relationship and its driving forces, which can support synergetic ES-BPS management in regions undergoing rapid urbanization. [ABSTRACT FROM AUTHOR]

The rapidly increasing prevalence of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the bla KPC– 2 gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the bla KPC– 2 gene have not been fully characterized. In this study, we report the complete genome sequences of two novel bla KPC– 2-harboring incompatibility group U (IncU) plasmids, pEC2341-KPC and pEC2547-KPC, from international high-risk clones of Escherichia coli isolated from Zhejiang, China. Two KPC-2-producing E. coli isolates (EC2341 and EC2547) were collected from clinical samples. Whole-genome sequencing (WGS) analysis indicated that EC2341 and EC2547 belonged to the ST410 and ST131 clones, respectively. S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and conjugation experiments confirmed the presence of the bla KPC– 2 gene on the pEC2341-KPC plasmid and that this was a conjugative plasmid, while the bla KPC– 2 gene on the pEC2547-KPC plasmid was a non-conjugative plasmid. In addition, plasmid analysis further revealed that the two bla KPC– 2-harboring plasmids have a close evolutionary relationship. To the best of our knowledge, this is the first report of E. coli strains carrying the bla KPC– 2 gene on IncU plasmids. The emergence of the IncU-type bla KPC– 2-positive plasmid highlights further dissemination of bla KPC– 2 in Enterobacteriaceae. Therefore, effective measures should be taken immediately to prevent the spread of these bla KPC– 2–positive plasmids. [ABSTRACT FROM AUTHOR]

The Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has become a serious problem because the species is wide ranging and there are few treatment options. Fosfomycin has attracted renewed interest in combination therapy for infections caused by KPC-producing K. pneumoniae isolates. Because of the increasing use of fosfomycin, resistant isolates have been continually reported in carbapenem-resistant K. pneumoniae (CRKP). At present, multiple mechanisms can result in fosfomycin resistance. However, there is limited knowledge with respect to plasmid-mediated fosfomycin resistance gene (fosA3) determinants in KPC-producing K. pneumoniae isolates. In this study, a total of 101 CRKP strains were collected from four hospitals in Zhejiang province from January 2013 to August 2014; 28.7% (29/101) of CRKP isolates were resistant to fosfomycin. Gene fosA3 was detected in 29 fosfomycin-resistant KPC-producing K. pneumoniae isolates, whereas genes fosA, fosB, fosB2, fosC, fosC2, and fosX were all negative among the resistant isolates. In addition, among 29 fosfomycin-resistant KPC-producing K. pneumoniae isolates, pulsed-field gel electrophoresis (PFGE) analysis revealed five pulsotypes. S1-PFGE and Southern blot showed that the fosA3 gene was located on an approximately 140-kb plasmid in all isolates. Eight of the 29 isolates (27.6%) tested could successfully transfer their fosfomycin-resistant phenotype to Escherichia coli strain J53. All fosA3-positive isolates were determined to have an identical genetic background, IS26-tetR-cadC-orf1-fosA3-IS26, which is the same as that of the fosA3-positive plasmid pFOS18 in China. The primary resistance mechanism to fosfomycin was caused by a plasmid-mediated fosA3. Furthermore, it is noteworthy that the plasmid genetically carrying a combination of the fosA3 and blaKPC-2 genes could accelerate the spread of antibiotic resistance. Effective and persistent monitoring and surveillance will be vital to prevent further dissemination of these resistance genes. [ABSTRACT FROM AUTHOR]