Nonvolatile multilevel adjustable optical switch based on plasmonic slot waveguide and GST segmented structure.

Optical computing has gradually demonstrated its efficiency in handling increasingly complex computational demands, attracting widespread attention. Optical switches can effectively control and modulate optical signals, providing flexibility and efficiency for optical computing systems. However, traditional optical switches face performance issues such as power consumption, switching speed, and compactness, severely limiting the implementation of large-scale photonic integrated circuits and optical neural networks. This paper proposes an innovative design structure for a non-volatile multi-level adjustable optical switch by combining a plasmonic slot waveguide with segmented phase-change materials. Modulation of waveguide light transmission is achieved by adjusting the phase state of Ge2Sb2Te5(GST). At a wavelength of 1550 nm, a low insertion loss of 0.5dB has been achieved, with approximately an 85% difference in optical transmittance between amorphous state (aGST) and crystalline state (cGST). The high transmittance difference contributes to achieving a wide range of weight variations and supports precise weight updates. Based on this design, we successfully implemented a handwritten digit recognition task with an accuracy of 95%, laying the foundation for future more efficient memory computing neural morphic networks.

Design, synthesis and triglyceride-lowering activity of tricyclic matrine derivatives for the intervention of non-alcoholic fatty liver disease.

Thirty new tricyclicmatrinic derivatives were successively synthesized and evaluated for their inhibitory activity on the accumulation of triglycerides (TG) in AML12 cells, using 12 N-m-trifluoromethylbenzenesulfonyl matrine (1) as the hit compound. Among the analogues, compound 7n possessing 11-trimethylbutylamine quaternary exerted the highest in vitro TG-lowering potency, as well as a good safety profile. 7n significantly attenuated the hepatic injury and steatosis, and ameliorated dyslipidemia and dysglycemia in the mice with non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet. Primary mechanism study revealed that upregulation of peroxisome proliferator-activated receptors α (PPARα)-carnitine palmitoyltransferase 1A (CPT1A) pathway mediated the efficacy of 7n. Our study provides powerful information for developing this kind of compound into a new class of anti-NAFLD candidates, and compound 7n is worthy of further investigation as an ideal lead compound.

Distribution and associations of anterior lens zonules lengths in patients with cataract.

PURPOSE: To investigate the characteristics and associations of anterior lens zonules lengths in cataract patients via ultrasound biomicroscope (UBM) measurement. METHODS: Patients with age-related cataracts and high myopic cataracts who planned to undergo cataract surgery were included in the study. After routine ophthalmic examinations, the UBM was performed on both eyes to get images of the anterior lens zonules, and Image J software was used to measure the lengths of the lens zonules. Axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and white-to-white (WTW) diameter of both eyes were obtained by IOL Master 700. Univariate and multivariate regression analyses were used to assess associated factors of anterior lens zonules lengths. RESULTS: Forty-nine patients with age-related cataracts and 33 patients with high myopic cataracts were enrolled. High myopic cataract patients were younger and had longer anterior lens zonules. Multivariate regression analysis showed that anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.036, P = 0.029; nasal location: ß = 0.034, P = 0.011; superior location: ß = 0.046, P = 0.002) and ACD (inferior location: ß = 0.305, P = 0.016) in right eyes. In left eyes, anterior lens zonules lengths were associated with axial lengths (temporal location: ß = 0.028, P = 0.017; inferior location: ß = 0.026, P = 0.016; nasal location: ß = 0.033, P < 0.001) and ACD (inferior location: ß = 0.215, P = 0.030; superior location: ß = 0.290, P = 0.011). CONCLUSIONS: High myopic cataract patients have longer anterior lens zonules. AL and ACD contributed to the lengths of anterior lens zonules. Thus, for patients with long AL and deeper ACD, lens zonules measurement was crucial. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn identifier is ChiCTR2300071397.

Atorvastatin reduces renal interstitial fibrosis caused by unilateral ureteral obstruction through inhibiting the transcriptional activity of YAP.

Renal interstitial fibrosis is the primary pathological basis for the progression and development of various chronic kidney diseases, ultimately leading to renal failure. Obstructive kidney disease caused by conditions such as kidney stones, is a common cause of renal fibrosis. The Hippo pathway is a crucial signaling pathway that senses mechanical forces and is involved in the pathophysiology of fibrosis. In this study, we established a mouse model of obstructive kidney disease induced by unilateral ureteral obstruction (UUO). The UUO procedure significantly upregulated YAP and fibrosis-related gene expression in a time-dependent manner. Morphologically, the renal fibrotic lesions associated with hydronephrosis progressively worsened over time in the UUO group. Atorvastatin, which is widely used to lower blood cholesterol levels, has recently been shown to inhibit Yes1 associated protein (YAP). We treated UUO mice with atorvastatin for 3 and 10 days and observed a decrease in the expression of YAP and fibrosis-related genes at the mRNA and protein levels, along with a reduction in the renal fibrosis analyzed by Masson's staining. These findings suggest that atorvastatin may serve as a preventive agent for fibrosis associated with obstructive kidney disease.

High-yield production of FK228 and new derivatives in a Burkholderia chassis.

FK228 (romidepsin) is the only natural histone deacetylases (HDACs) inhibitor approved by FDA to treat cutaneous and peripheral T-cell lymphoma. However, the limited supply and severe cardiotoxicity of FK228 underscore the importance to develop an effective synthetic biology platform for the manufacturing and fine-tuning of this drug lead. In this work, we constructed a Burkholderia chassis for the high-yield production of FK228-family (unnatural) natural products. By virtue of the optimized Burkholderia-specific recombineering system, the biosynthetic gene cluster (BGC) encoding the FK228-like skeleton thailandepsins (tdp) in Burkholderia thailandensis E264 was replaced with an attB integration site to afford the basal chassis KOGC1. The tdp BGC directly captured from E264 was hybridized with the FK228-encoding BGC (dep) using the versatile Red/ET technology. The hybrid BGC (tdp-dep) was integrated into the attB site of KOGC1, resulting in the heterologous expression of FK228. Remarkably, the titer reached 581 mg/L, which is 30-fold higher than that of native producer Chromobacterium violaceum No. 968. This success encouraged us to further engineer the NRPS modules 4 or 6 of hybrid tdp-dep BGC by domain units swapping strategy, and eight new FK228 derivatives (1-8) varying in the composition of amino acids were generated. Especially, the titers of 2 and 3 in KOGC1 were up to 985 mg/L and 453 mg/L, respectively. 2 and 3 displayed stronger cytotoxic activity than FK228. All in all, this work established a robust platform to produce FK228 and its new derivatives in sufficient quantities for anticancer drug development.

LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.

Proinflammatory stimuli elicit rapid transcriptional responses via transduced signals to master regulatory transcription factors. To explore the role of chromatin-dependent signal transduction in the atherogenic inflammatory response, we characterized the dynamics, structure, and function of regulatory elements in the activated endothelial cell epigenome. Stimulation with tumor necrosis factor alpha prompted a dramatic and rapid global redistribution of chromatin activators to massive de novo clustered enhancer domains. Inflammatory super enhancers formed by nuclear factor-kappa B accumulate at the expense of immediately decommissioned, basal endothelial super enhancers, despite persistent histone hyperacetylation. Mass action of enhancer factor redistribution causes momentous swings in transcriptional initiation and elongation. A chemical genetic approach reveals a requirement for BET bromodomains in communicating enhancer remodeling to RNA Polymerase II and orchestrating the transition to the inflammatory cell state, demonstrated in activated endothelium and macrophages. BET bromodomain inhibition abrogates super enhancer-mediated inflammatory transcription, atherogenic endothelial responses, and atherosclerosis in vivo.

Brd4 participates in epigenetic regulation of the extinction of remote auditory fear memory.

BACKGROUND: Inaccurate fear memories can be maladaptive and potentially portrait a core symptomatic dimension of fear adaptive disorders such as post-traumatic stress disorder (PTSD), which is generally characterized by an intense and enduring memory for the traumatic events. Evidence exists in support of epigenetic regulation of fear behavior. Brd4, a member of the bromodomain and extra-terminal domain (BET) protein family, serves as a chromatin "reader" by binding to histones in acetylated lysine residues, and hence promotes transcriptional activities. However, less is known whether Brd4 participates in modulating cognitive activities especially memory formation and extinction. Here we provide evidence for a role of Brd4 in modulation of auditory fear memory. Auditory fear conditioning resulted in a biphasic Brd4 activation in the anterior cingulate cortex (ACC) and hippocampus of adult mice. Thus, Brd4 phosphorylation occurred 6 h and 3-14 days, respectively, after auditory fear conditioning. Systemic inhibition of Brd4 with a BET inhibitor, JQ1, impaired the extinction of remote (i.e., 14 days after conditioning) fear memory. Further, conditional Brd4 knockout in excitatory neurons of the forebrain impaired remote fear extinction as observed in the JQ1-treated mice. Herein, we identified that Brd4 is essential for extinction of remote fear in rodents. These results thus indicate that Brd4 potentially plays a role in the pathogenesis of PTSD.

BET bromodomain proteins regulate enhancer function during adipogenesis.

Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation. Inhibition of the bromodomain and extraterminal domain (BET) family of bromodomain-containing proteins impedes BRD4 occupancy at these de novo enhancers and disrupts transcription of Pparg and Cebpa, thereby blocking adipogenesis. Furthermore, silencing of these BRD4-occupied distal regulatory elements at the Pparg locus by CRISPRi demonstrates a critical role for these enhancers in the control of Pparg gene expression and adipogenesis in 3T3L1s. Together, these data establish BET bromodomain proteins as time- and context-dependent coactivators of the adipocyte cell state transition.

In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015-2018.

BACKGROUND: Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. METHODS: In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. RESULTS: In 2015-2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. CONCLUSIONS: Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.

Bromodomain-containing protein 4 contributes to renal fibrosis through the induction of epithelial-mesenchymal transition.

Fibrosis is a common pathology in renal disease. Hypertensive nephropathy (HN) is one of the most common secondary nephropathies that often progresses to severe renal fibrosis with limited treatment options beyond hypertension control. Bromodomain-containing protein 4 (Brd4) was recently recognized as a target in signaling pathways that underlie the pathologies of inflammatory diseases and tumors. A recently developed inhibitor of Brd4, JQ1, has been shown to exert antifibrotic effects and is being clinically explored as an anti-inflammatory and antitumor drug. Here, using human kidney biopsies and Angiotensin II-induced mouse fibrotic kidney samples, we show that Brd4 was upregulated in renal tissue from HN patients and hypertensive mouse models. In mice, JQ1 alleviated Angiotensin II-induced kidney fibrosis and blocked epithelial-mesenchymal transition (EMT) by altering the expression of EMT-related proteins. Using an in vitro model of HK2 cells exposed to Angiotensin II, we also demonstrated that JQ1 suppressed the protein expression of fibrotic genes in these cells. These results further implicate Brd4 in the fibrotic response in HN and reveal that Brd4 is a potential antifibrotic target. BET inhibitors are currently being investigated in clinical trials as antitumor agents and show potent pharmacological effects. Our findings suggest that BET inhibitors may also be potential translational therapies for HN.

Lovastatin attenuates angiotensin II induced cardiovascular fibrosis through the suppression of YAP/TAZ signaling.

Angiotensin II (ANG II) is associated with fibrosis in both clinical and basic studies. Thus, we aimed to explore a mechanism by which ANG II induces fibrosis. 5 µM of ANG II was used in the in vitro study. The mouse cardiovascular fibrosis model was established by infused with AngII (1000 ng/kg/min) for 7 days and cotreated with lovastatin (10 mg/kg daily) or vehicle control (DMSO in saline). We found that ANG II activated yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), two transcription factors that were shown to induce fibrosis. Inhibition of ras homolog gene family member A (RhoA) reduced ANG II-induced YAP/TAZ transcriptional activity, which suggests that the upregulation of YAP/TAZ signaling by ANG II is RhoA-dependent. Furthermore, studies have shown that the inhibition of YAP/TAZ by either siRNA or small molecule inhibitor suppressed ANG II-induced expression of fibrogenic genes, indicating that ANG II upregulates YAP/TAZ to initiate fibrosis. The mevalonate pathway, which is targeted by statins, has also been shown to control YAP/TAZ. Here, we found that the suppression of YAP/TAZ signaling by lovastatin attenuates ANG II-induced fibrosis, both in vitro and in vivo. These data reveal a novel mechanism for ANG II in the induction of fibrosis. In addition, our findings provide a reasonable explanation regarding the mechanism by which statins improve fibrosis in patients with cardiovascular and renal diseases.

Quantitative Proteomic Analysis of Castor (Ricinus communis L.) Seeds During Early Imbibition Provided Novel Insights into Cold Stress Response.

Early planting is one of the strategies used to increase grain yield in temperate regions. However, poor cold tolerance in castor inhibits seed germination, resulting in lower seedling emergence and biomass. Here, the elite castor variety Tongbi 5 was used to identify the differential abundance protein species (DAPS) between cold stress (4 °C) and control conditions (30 °C) imbibed seeds. As a result, 127 DAPS were identified according to isobaric tag for relative and absolute quantification (iTRAQ) strategy. These DAPS were mainly involved in carbohydrate and energy metabolism, translation and posttranslational modification, stress response, lipid transport and metabolism, and signal transduction. Enzyme-linked immunosorbent assays (ELISA) demonstrated that the quantitative proteomics data collected here were reliable. This study provided some invaluable insights into the cold stress responses of early imbibed castor seeds: (1) up-accumulation of all DAPS involved in translation might confer cold tolerance by promoting protein synthesis; (2) stress-related proteins probably protect the cell against damage caused by cold stress; (3) up-accumulation of key DAPS associated with fatty acid biosynthesis might facilitate resistance or adaptation of imbibed castor seeds to cold stress by the increased content of unsaturated fatty acid (UFA). The data has been deposited to the ProteomeXchange with identifier PXD010043.

Carbapenem susceptibilities of Gram-negative pathogens in intra-abdominal and urinary tract infections: updated report of SMART 2015 in China.

BACKGROUND: To evaluate the susceptibility rates of aerobic and facultative Gram-negative bacterial isolates from Chinese intra-abdominal infections (IAI) and urinary tract infections (UTI) focusing on carbapenems and comparing their effectiveness between 2014 and 2015. METHODS: A total of 2318 strains in 2015 (1483 from IAI and 835 from UTI) and 2374 strains in 2014 (1438 from IAI and 936 from UTI) were included in the analysis. Antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. Hospital acquired (HA) IAI and UTI were defined as isolates sampled > 48 h and community acquired (CA) as isolates sampled < 48 h after admission. RESULTS: The main species derived from IAI and UTI in 2015 were Escherichia coli (50.86%) and Klebsiella pneumoniae (19.20%). Susceptibilities of Escherichia coli IAI and UTI strains to imipenem (IPM) and ertapenem (ETP) were > 90% in 2014 and 2015, while the susceptibilities to IPM and ETP of Klebsiella pneumoniae IAI strains were >  80% in 2014 but dropped to ≤80% in 2015 for UTI strains. Susceptibilities of IAI Enterobacteriaceae strains to IPM and ETP in 2015 were lowest in the colon and abscesses, and Enterobacteriaceae susceptibilities of UTI and IAI isolates to IPM and ETP were lowest in medical, pediatric and surgery intensive care units (ICUs) in 2015. CONCLUSIONS: IPM and ETP were effective in vitro against Enterobacteriaceae isolated from IAIs and UTIs in 2014 and 2015, but susceptibility to carbapenems in UTIs markedly decreased in 2015.

Using the 6RLKu Minichromosome of Rye (Secale cereale L.) to Create Wheat-Rye 6D/6RLKu Small Segment Translocation Lines with Powdery Mildew Resistance.

Long arms of rye (Secale cereale L.) chromosome 6 (6RL) carry powdery mildew resistance genes. However, these sources of resistance have not yet been successfully used in commercial wheat cultivars. The development of small segment translocation chromosomes carrying resistance may result in lines carrying the 6R chromosome becoming more commercially acceptable. However, no wheat-rye 6RL small segment translocation line with powdery mildew resistance has been reported. In this study, a wheat-rye 6RLKu minichromosome addition line with powdery mildew resistance was identified, and this minichromosome was derived from the segment between L2.5 and L2.8 of the 6RLKu chromosome arm. Following irradiation, the 6RLKu minichromosome divided into two smaller segments, named 6RLKumi200 and 6RLKumi119, and these fragments participated in the formation of wheat-rye small segment translocation chromosomes 6DS/6RLKumi200 and 6DL/6RLKumi119, respectively. The powdery mildew resistance gene was found to be located on the 6RLKumi119 segment. Sixteen 6RLKumi119-specific markers were developed, and their products were cloned and sequenced. Nucleotide BLAST searches indicated that 14 of the 16 sequences had 91⁻100% similarity with nine scaffolds derived from 6R chromosome of S. cereale L. Lo7. The small segment translocation chromosome 6DL/6RLKumi119 makes the practical utilization in agriculture of powdery mildew resistance gene on 6RLKu more likely. The nine scaffolds are useful for further studying the structure and function of this small segment.

Super enhancers at the miR-146a and miR-155 genes contribute to self-regulation of inflammation.

Inflammatory response is essential to host defense and repair, and requires tight regulation as excessive and constant inflammatory response is deleterious. We recently identified that one of the general but key mechanisms for inflammatory gene transcription regulation is controlled by the formation of super enhancers mediated by NF-κB, and bromodomain and extraterminal (BET) proteins. Given that microRNA transcription shares a similar mechanism to mRNA, we assume that the inflammatory microRNAs transcription could be NF-κB and BET bromodomain dependent. In the present study, we confirmed that inflammatory stimuli changed human umbilical vein endothelial cells (HUVEC) microRNA profile. Among these microRNAs, miR-146a and miR-155, two well-established inflammatory microRNAs, are both downregulated at transcriptional level by NF-κB and BET bromodomain inhibition. To pursue this mechanism, we analyzed the ChIP-seq data and found that NF-κB, BRD4 and RNA POL II were rapidly distributed at the upstream regions of miR-146a and miR-155, and more importantly mediated the formation of the super enhancers that drive miR-146a and miR-155 transcription. These microRNAs transcription driven by super enhancers in turn downregulate both in vitro and in vivo canonical inflammatory genes expression through targeting inflammatory mediators. This novel finding demonstrated how the host self-regulates inflammatory genes expression at both transcriptional and post-transcriptional level to ensure the appropriate level of the host inflammatory response.

BET bromodomain is a novel regulator of TAZ and its activity.

Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/ß-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood. Here, we found that BET bromodomain inhibition upregulated TAZ protein and its transcriptional output, independent of its well-established role as a mediator of Hippo and Wnt signaling. Additionally, JQ1, a synthetic BET inhibitor, suppressed Wnt/ß-catenin activity by upregulating TAZ. Although JQ1 upregulated TAZ, which is known to promote cell proliferation, it drastically suppressed the growth of colon cancer cells by inducing cell cycle arrest. Collectively, our study identified an unexpected transcriptional repression function of the BET bromodomain and a novel mechanism for TAZ upregulation.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.