Spatiotemporal and direct capturing global substrates of lysine-modifying enzymes in living cells.

Protein-modifying enzymes regulate the dynamics of myriad post-translational modification (PTM) substrates. Precise characterization of enzyme-substrate associations is essential for the molecular basis of cellular function and phenotype. Methods for direct capturing global substrates of protein-modifying enzymes in living cells are with many challenges, and yet largely unexplored. Here, we report a strategy to directly capture substrates of lysine-modifying enzymes via PTM-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner. By integrating enzymatic PTM-mechanisms, and genetically encoding residue-selective photo-crosslinker into PTM-enzymes, our strategy expands the substrate profiles of both bacterial and mammalian lysine acylation enzymes, including bacterial lysine acylases PatZ, YiaC, LplA, TmcA, and YjaB, as well as mammalian acyltransferases GCN5 and Tip60, leading to discovery of distinct yet functionally important substrates and acylation sites. The concept of direct capturing substrates of PTM-enzymes via residue crosslinking may extend to the other types of amino acid residues beyond lysine, which has the potential to facilitate the investigation of diverse types of PTMs and substrate-enzyme interactive proteomics.

Role of comprehensive geriatric assessment in screening for mild cognitive disorders.

BACKGROUND: The role of comprehensive geriatric assessment (CGA) in screening for mild cognitive disorders was not known. AIM: To evaluate the role of CGA in screening for mild cognitive disorders. METHODS: A total of 100 elderly people who underwent health examinations in our hospital and community between January 2020 and December 2021 were included for analysis. Using Petersen as the diagnostic gold standard, healthy individuals were included in the control group and patients with mild cognitive impairment were assigned to the study group. The correlation between the cognitive function of the patients and their baseline clinical profiles was analyzed. Patients' Montreal Cognitive Assessment (MoCA) and CGA screening results were compared, and the sensitivity and specificity were calculated to assess the screening role of CGA. RESULTS: CGA assessment yielded higher diagnostic accuracy than MoCA. The results of the multivariate regression analysis showed no correlation of gender, age, body mass index and literacy with cognitive function. Patients with mild cognitive impairment obtained significantly lower MoCA scores than healthy individuals (P < 0.05). In the CGA scale, patients with mild cognitive impairment showed significantly lower Mini-mental State Examination, Miniature Nutritional Assessment and Berg Balance Scale scores, and higher Activity of Daily Living, Instrumental Activities of Daily Living Scale and Frailty Screening Inventory scores than healthy individuals (P < 0.05), whereas the other assessment scales showed no significant differences (P > 0.05). The CGA provides higher diagnostic sensitivity and specificity than the MoCA (P < 0.05). CONCLUSION: CGA allows accurate identification of mild cognitive impairment with high sensitivity and specificity, facilitating timely and effective intervention, and is thus recommended for clinical use.

Aortic intramural hematoma presenting as paraplegia progressed into segmental aortic dissection.

Intramural hematoma (IMH) is a newly defined disease entity and the optimal management is still controversial as the disease shows varied clinical course. We present a case of type B IMH, initially presenting with paraplegia progressing to segmental aortic dissection (SAD) which the formed dissection displayed as a segmental distribution pattern. To our knowledge, it may become a new progression pattern of IMH progression. The SAD was successfully treated with both thoracic and abdominal endovascular aortic repair (TEVAR plus EVAR). In 1-year follow-up, the patient recovered almost completely with moderately neurological deficit and the blood pressure is in control.

Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation.

The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

Toxic Epidermal Necrolysis Induced by Sintilimab: A Case Report

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Preoperative Evaluation and Endovascular Procedure of Intraoperative Aneurysm Rupture During Thoracic Endovascular Aortic Repair.

Thoracic aortic aneurysms are now routinely repaired with endovascular repair if anatomically feasible because of advantages in safety and recovery. However, intraoperative aneurysm rupture is a severe complication which may have an adverse effect on the outcome of treatment. Comprehensive preoperative assessment and considerate treatment are keys to success of endovascular aneurysm repair, especially during unexpected circumstances. Few cases have reported on intraoperative aortic rupture, which were successfully managed by endovascular treatment. Here, we present a rare case of an intraoperative aneurysm rupture during endovascular repair of thoracic aortic aneurysm with narrow neck and angulated aorta arch (coarctation-associated aneurysm), which was successfully treated using double access route approach and iliac limbs of infrarenal devices. LEVEL OF EVIDENCE: Level 5.

A multicenter analysis of bacteria distribution and antimicrobial resistance of bloodstream infection in Yunnan, 2017-2021 / 中国热带医学

@#Abstract: Objective　To analyze the distribution and drug resistance evolution characteristics of pathogenic bacteria of bloodstream infection in nine tertiary hospitals in Yunnan Province from 2017 to 2021, so as to provide reliable basis for rational selection of antibiotics in clinic. Methods Using the drug sensitive paper method or instrument method, the bacteria identification and drug sensitivity test were carried out in nine tertiary hospitals in different regions according to the unified technical scheme. The results were judged according to the Clinical and Laboratory Standards Institute (CLSI) breakpoint standard in 2021, and use WHONET5.6 for data statistical analysis. Results A total of 12 003 strains of pathogenic bacteria were isolated from bloodstream infection samples in the past five years, including 7 442 strains of Gram-negative bacteria (62.0%) and 4562 strains of Gram-positive bacteria (38.0%), with an increasing trend in the number of isolated strains; of these, 163 strains (1.4%) were isolated from outpatients and 11 840 strains (98.6%) were isolated from inpatients. The top three gram-negative bacteria were Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, of which 309 strains (4.2%) were carbapenem-resistant Klebsiella pneumoniae (CR-KPN), 29 strains (0.4%) carbapenem-resistant Escherichia coli and 19 strains (0.3%) carbapenem-resistant Enterobacter cloacae, and the number of CR-KPN was on the rise year by year. The top three Gram-positive bacteria were coagulase-negative staphylococci, Staphylococcus aureus and Enterococcus faecium, of which methicillin-resistant Staphylococcus aureus (MRSA) was detected for 213 strains, accounting for 27.7%, and decreased from 40.0% in 2017 to 23.4% in 2021, showing a downward trend year by year. No vancomycin-resistant staphylococci and enterococci were found. Conclusions The detection and composition of bloodstream infection pathogenic bacteria in multicenter have not changed much in the past five years, but each hospital has its own characteristics. The number of carbapenem resistant Enterobacteriaceae increased year by year, which should be paid more attention.

Report of a case of Leuconostoc lactis bacteremia following intestinal perforation with literature review / 中华全科医师杂志

A 24-year female with abdominal pain and fever for 4 days was admitted. The blood culture showed Leuconostoc growth, and sputum culture showed positive Acinetobacterbaumannii. The diagnosis Leuconostoclactis bacteremia following small intestinal perforation was confirmed; surgical treatment was performed and the infection was controlled by piperacillin sodium and tazobactam combined with tegacycline. Wanfang database, CNKI, PubMed and Embase database up to September 2020 were searched with the keywords of " Leuconostoc lactis" "infection" "bacteraemia" for relevant literature. A total of 32 cases were reported in the literature, of whom 13 (39.4%) were infants, 17 (51.5%) had catheter-related bloodstream infection, and one healthy adult male had bacteremia through gastrointestinal perforation. In 20 patients treated with penicillins-based antibiotics, 18 were cured with an effective rate of 90.0%. The results suggest that Leuconostoc infection is likely to occur in the infants, but adults can still get community-acquired Leuconostoc infection. Most β-lactams are susceptible to Leuconostoc, but some exhibit resistance, so it is recommended to select antimicrobial agents based on drug susceptibility.

N-methyl-N'-nitro-N-nitrosoguanidine sensitivity, mutator phenotype and sequence specificity of spontaneous mutagenesis in FEN-1-deficient cells.

Intact pZ189 DNA was allowed to replicate in FL-FEN-1(-) cell line that was established in this laboratory in which the expression of FEN-1 gene was blocked by dexamethasone-inducible expression of antisense RNA to FEN-1. E. coli MBM7070 was transfected with the replicated plasmid, and those with mutations in the supF gene were identified. The frequency of mutants that did not contain recognizable changes in the electrophoretic mobility of the plasmid DNA was scored. The frequency of such mutants was 19.1 x 10(-4) (34/17781), significantly higher than those of 2.9 x 10(-4) (4/13668) and 3.0 x 10(-4) (3/9857) in the corresponding controls, respectively. Sequence analysis of the supF genes of these mutants showed that all (37/37) the base substitutions occurred at C:G base pairs; 68% (23/37) of the base substitutions were base transversions, while 32% (12/37) were transitions. Approximately 76% (23/37) of these base substitutions occurred frequently at nine positions; two of these sites contain triple pyrimidine (T or C) repeat upstream to the mutated base; four of these sites consist of 5'-TTN1N2 and mutations occurred at N1 site sequence; another two sites have the characteristics of triple A flanked at both 5' and 3' side by TCT, with the base substitution occurring at C in the context sequence. These data suggested that these sites are the hot spot of mutagenesis in plasmid replicated in FEN-1-deficient cells. Besides the mutator phenotype of the FEN-1-deficient cell, it was also demonstrated that FEN-1-deficient cell exhibited an increased N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) sensitive phenotype.

Establishment of Cell Line with the FEN-1 Gene Blocked by Its Antisense.

FEN-1 is a structure-specific endo/exonuclease, which is involved in the process of both DNA duplication and DNA repair. In this work a mammalian expression vector expressing antisense FEN-1 gene fragment pMAMneoAmp(-)FNB(-) was constructed, after cloning the NcoI-BamHI fragment of FEN-1 gene into the mammalian expression vector pMAMneoAmp(-) in antisense orientation. After FL cell was transfected with pMAMneoAmp(-)FNB(-) and selected by G418, the FL-FEN-1(-) cell line, in which the FEN-1 gene expression was blocked, was established. It was found that the growth of FL-FEN-1(-) was decreased upon the induction with dexamethasone and its T(D) was 3.03 d, while the T(D) of controls FL and FL-M induced with dexamethasone was 2.03 and 2.22 d, respectively, and the T(D) of the FL-FEN-1(-) cell without dexamethasone was 2.38 d.

The Influence of FEN-1 Gene on Cell Cycle and Genetic Stability.

FEN-1 is essential in the cell replication, repair and in the maintenance of cellular genetic stability. In this report, it was verfied that FEN-1 antisense mRNA fragment was expressed in the cell line FL-FEN-1(-),constructed in our lab, blocking FEN-1 gene expression. It was found by the flow cytometer analysis that the cell cycle of FL-FEN-1(-) cells was delayed in the S-phase DNA synthesis process and arrested in G(1) phase. In a mutation assay, based on the shuttle-plasmid pZ189, the spontaneous mutation frequency of SupF tRNA gene in the plasmid in the FL-FEN-1(-) cells was 19.1x10(4),while it was 2.9x10(4) and 3.0x10(4) in the control cells FL and FL-M, respectively. Further study showed that nontargeted mutation frequency of the FL-FEN-1(-) cell induced by MNNG was almost the same as the control, indicating that the mutants derived from the block of FEN-1 gene and the nontargeted mutants may be formed through different passways. The FL-FEN-1(-) cells exhibit increased sensitivity to alkylating agent MNNG.

Synthesis of AHPN Derivatives and Their Combining Activities with RARγ / 中国药学杂志

OBJECTIVE: To study the synthesis and activities of AHPN derivatives. METHODS: Starting from p-bromophenol and 1-adamantanol, a series of AHPN derivatives were synthesized by substitution reaction, condensation reaction, oxidation reaction and reduction reaction. These new compounds were characterized by 1H-NMR, 13CNMR and HR-MS. Biacore technique was used to test the derivatives' combining activities with RARγ. RESULTS: Four compounds, 7c, 6c, 6e, and 6h, exhibited significant combining activities with RARγ compared with AHPN. The introduction of phosphoric acid groups and nitrogen heterocyclic ring increased the activities of these compounds. CONCLUSION: Compounds 7c, 6c, 6e, and 6h show significant combining activities with RARγ, which are worthy of further study.

Antimicrobial resistance profile of clinical isolates in hospitals across China: report from the CHINET Surveillance Program, 2017 / 中国感染与化疗杂志

Objective To investigate the antimicrobial resistance profile of the clinical isolates collected from selected hospitals across China. Methods Twenty-nine general hospitals and five children's hospitals were involved in this program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Results were interpreted according to CLSI 2017 breakpoints. Results A total of 190 610 clinical isolates were collected from January to December 2017, of which gram negative organisms accounted for 70.8％ (134 951/190 610) and gram positive cocci 29.2％ (55 649/190 610). The prevalence of methicillin-resistant strains was 35.3％ in S. aureus (MRSA) and 80.3％ in coagulase negative Staphylococcus (MRCNS) on average. MR strains showed much higher resistance rates to most of the other antimicrobial agents than MS strains. However, 91.6％ of MRSA strains were still susceptible to trimethoprim-sulfamethoxazole, while 86.2％ of MRCNS strains were susceptible to rifampin. No staphylococcal strains were found resistant to vancomycin. E. faecalis strains showed much lower resistance rates to most of the drugs tested (except chloramphenicol) than E. faecium. Vancomycin-resistant Enterococcus (VRE) was identified in both E. faecalis and E. faecium. The identified VRE strains were mainly vanA, vanB or vanM type based on phenotype or genotype. The proportion of PSSP or PRSP strains in the non-meningitis S.pneumoniae strains isolated from children decreased but the proportion of PISP strains increased when compared to the data of 2016. Enterobacteriaceae strains were still highly susceptible to carbapenems. Overall, less than 10％ of these strains (excluding Klebsiella spp.) were resistant to carbapenems. The prevalence of imipenem-resistant K. pneumoniae increased from 3.0％ in 2005 to 20.9％ in 2017, and meropenem-resistant K. pneumoniae increased from 2.9％ in 2005 to 24.0％ in 2017, more than 8-fold increase. About 66.7％ and 69.3％ of Acinetobacter (A. baumannii accounts for 91.5％) strains were resistant to imipenem and meropenem, respectively. Compared with the data of year 2016, P. aeruginosa strains showed decreasing resistance rate to carbapenems. Conclusions Bacterial resistance is still on the rise. It is necessary to strengthen hospital infection control and stewardship of antimicrobial agents. The communication between laboratorians and clinicians should be further improved in addition to surveillance of bacterial resistance.

Interferences and suppression methods in use of medical electronic devices / 医疗卫生装备

Objective To explore the methods for suppressing the interferences during the application of medical electronic devices.Methods Kinds of signal sources interfering medical electronic devices were analyzed,and the suppression methods were discussed from the aspects of shielding protection,selection of ground point,filtering,circuit design and etc.Results Interference suppression could be executed by proper grounding,shielding protection,component protection and etc.Conclusion Suppression methods have to be selected according to inference source during the clinical application of medical electronic devices.

Investigation of antimicrobial susceptibility of Pseudomonas aeruginosa of Yunnan,China in 2014 / 国际检验医学杂志

Objective To investigate the distribution and antibiotic resistance of clinical Pseudomonas aeruginosa in Yunnan provincal of China in 2014.Methods Pseudomonas aeruginosa were collected from 28 hospitals in Yunnan surveillance of China.All hospitals were carried with the unified solution for bacteria culture,isolation,identification and antibiotic sensitivity tests according to CLSI M100-S24.The data of 2 873 strains pseudomonas aeruginosa were analyzed by WHONET5.6 software.Results 2 873 clinical strains of non-repetitive Pseudomonas aeruginosa isolates,90.36%were isolated from hospitalized patients and 60.32% from sputum,8.42% from urine,8.11% from secretion,4.70% from abscess,2.92% from blood,etc.The sensitive rates of common antimicrobial agents of Pseudomonas aeruginosa in top five were turn amikacin (88.7%),piperacillin/he azole temple (85.0%),tobramycin (83.1%),piperacillin (80.3%) and cefepime (80.1%).59.0% of the Pseudomonas aeruginosa strains were resistant to Aztreonam.20.9%-29.7% of the Pseudomonas aeruginosa strains were resistant to Imipenem,Ceftazidime,Meropenem,Ciprofloxacin and Levofloxacin.The Pseudomonas aeruginosa isolates showed the lowest resistance rate (10.3%-19.9%) to Piperacillin,Gentamicin,Cefepime,Tobramycin,Piperacillin/Tazobactam and Amikacin.Conclusion The antimicrobial susceptibility pattern varies widly with Pseudomonas aeruginosa isolated in Yunnan of China in 2014.Antimicrobial resistance sur-Monitoring the antibiotic resistant trend of Pseudomonas aeruginosa and implementing the nosocomial infection control policy become more important in hospital management setting.

The Distribution and Drug-resistance of Gram-negative Bacilli among Blood Stream Infection in Yunnan Province of China during 2012 ～ 2014 / 昆明医科大学学报

Objective To learn the species distrilbution and drug-resistance of Gram-negative bacilli among bloodstream infections (BSI) in Yunnan province of China during 2012 to 2014.Methods Bloodstream infected Gram-negative bacilli were collected from 28 general hospitals in Yunan province of China.Data from all hospitals were applied with the same method of bacteria culture,isolation,identification and antibiotic sensitivity tests.WHONET 5.6 was used to perform the statistical analysis.Results A total of 9042 clinical strains of non-repetitive gram-negative bacilli were collected.Enterobacteriaceae and Non-fermenter bacteria accounted for 82.4％ and 17.6％ respectively.Enterobacteriaceae were mainly composed of Escherichia coli and Klebsiella pneumoniae.Non-fermenter bacteria were mainly composed of Acinetobacter baumannii and Pseudomonas aerouginosa.Escherichia coli accounted for the majority 49.29％,other species were Klebsiella pneumoniae 13.17％,Acinetobacter baumannii 4.04％ and Pseudomonas aeroginosa 3.85％.The susceptible rate of Enterobacteriaceae strains to the first generation cephalosporin was lower than 60％.The susceptible rate of E coli and Klebsiella pneumoniae to impenem was close to 100％,to Amikacin was more than 85％,to piperacillin-tazobactam was more than 70％,to Cefepime was more than 70％.But the susceptible rate of Klebsiella pneumoniae to impnem and amikacin decreased year by year from 2012 to 2014.The susceptible rate of Enterobacter cloacae to Amikacin was 86.4％ ～ 93.6％,Ciprofloxacin 70.5 ～ 76％,Cefepime 72.1 ～ 82.8％.It was less than other Enterobacteriaceae.The susceptible rate of Non-fermenter bacteria to normal antibiotics was much lower than Enterobacteriaceae.The susceptible rates of Pseudomonas aeroginosa to Impnem was 58.9％,Tobramycin 85％,Ciprofloxacin 71.7％,Amikacin 82.9％,Piperacillintazobactam 75.3％,Piperacillin59.6％,Atreonam 46.5％,Ceftazidime 69.1％ and Cefepime 68.9％ respectively.Furthermore,Acinetobacter baumannii's durg-resistance was more severe.The susceptible rate of Acinetobacter baumannii was lower than 30％,to the third and fourth generation cephalosporin,the susceptible rate of Ampicillin/Sulbactam,Cefoperazone/Sulbactam,Carbapenems,Piperacillin/Tazuobatan,Quinolones and Carbapenems was less than 40％.Conclusion Gram-negative bacilli have low susceptibilities among BSI.E.coli is the most common pathegon among BSI.The resistant rate of Non-fermenter bacteria to normal antibiotics is severe in hospitals.

Changing susceptibility ofKlebsiella strains in hospitals across China：data from the CHINET Antimicrobial Resistance Surveillance Program, 2005-2014 / 中国感染与化疗杂志

Objective To evaluate the changing pattern of antibiotic resistance inKlebsiella strains isolated from the patients in 19 hospitals across China based on the data from CHINET Antimicrobial Resistance Surveillance Program during the period from 2005 through 2014.Methods Kirby-Bauer disk diffusion and automated susceptibility testing methods were used to test the susceptibility ofKlebsiella isolates to the commonly used antibiotics. The results were interpreted according to the criteria of the Clinical and Laboratory Standards Institute (CLSI) Performance Standards for Antimicrobial Susceptibility Testing (CLSI-2014).Results A total of 61 406Klebsiella strains were identified between 2005 and 2014, includingK. pneumoniae (56 281 strains), K. oxytoca(4 779),Klebsiella pneumoniae subsp.Ozaenae (300) and otherKlebsiella species (46). Most (89.0%, 54 664/61 406) of theKlebsiella strains were isolated from inpatients, and 60.0% (36 835/61 406) were from respiratory tract speciems. About 16.7% (10 248/61 406) of the strains were isolated from pediatric patients aged 0-17 years and 83.3% (51 158/61 406) from adult patients. The prevalence ofKlebsiella spp. increased with time from 10.1% in 2005 to 14.3% in 2014. Based on the surveillance data during the 10-year period, we found a marked increase of resistance to imipenem (2.9% to 10.5%) and meropenem (2.8% to 13.4%) inKlebsiella spp. The prevalence of ESBLs-producing isolates inK. pneumoniae andK. oxytoca decreased from 39.0% in 2005 to 30.1% in 2014. The resistance to amikacin, ceftazidime, ciprolfoxacin, pipracillin-tazobactam and cefoperazone-sulbactam was on decline. The resistance rate to cefotaxime remained high about 49.5%. Carbapenem resistantance was identiifed in 5 796 (9.4%) of the isolates, including 5 492 strains ofK. pneumoniae and 280 strains ofK. oxytoca. Overall, 4 740 (7.8%) strains were identiifed as extensively-drug resistant (XDR), including 4 520 strains ofK. pneumoniae and 202 strains ofK. oxytoca. The carbapenem-resistant strains showed high (>60%) resistance rate to majority of the antimicrobial agents tested, but relatively low resistance to tigecycline (16.8%), amikacin (54.4%), and trimethoprim-sulfamethoxazole (55.5%).Conclusions During the 10-year period from 2005 through 2014, carbapenem resistance amongKlebsiella isolates has increased dramatically in the hospitals across China. The level of resistance to other antibiotics remains stable.

Antibiotic resistance profile of Enterobacter in hospitals across China：data from CHINET Antimicrobial Resistance Surveillance Program from 2005 through 2014 / 中国感染与化疗杂志

Objective To investigate the distribution and antibiotic resistance proifle of clinicalEnterobacter isolates using the data from CHINET during the period from 2005 through 2014.Methods A total of 20 558 clinical strains ofEnterobacter spp. were collected from 2005 to 2014 in CHINET Antimicrobial Resistance Surveillance Program. Antimicrobial susceptibility testing was performed with Kirby-Bauer or minimum inhibitory concentration method. The results were analyzed according to CLSI 2014 breakpoints.ResultsEnterobacter cloacae andEnterobacter aerogenes accounted for 71.1% (14 617/20558) and 20.1% (4 129/20 558) of all theEnterobacterisolates, respectively. The proportion ofEnterobacter spp. increased with time from 3.5% in 2005 to 4.3% in 2014. The main source of the isolates was respiratory tract, accounting for 55.2% (11 358/20 558). More than 90% of theEnterobacterisolates were resistant to cefazolin and cefoxitin, but less than 30% of the strains were resistant to cefepime, piperacillin-tazobactam, cefoperazone-sulbactam, amikacin, gentamicin, ciprolfoxacin, meropenem, imipenem and ertapenem. TheEnterobacterisolates showed a trend of declining resistance to most antibiotics except ertapenem and meropenem. The resistance proifle ofEnterobacterisolates varied with departments where they were isolated. The strains from ICU and Department of Surgery were relatively more resistant to antibiotics. The prevalence of multi-drug resistant (MDR) strains was decreasing, but the prevalence of carbapenem-resistantEnterobacter (CRE, resistant to any of imipenem, meropenem or ertapenem) was increasing. The MDR and CRE strains were primarily isolated from ICU and Department of Surgery. At least 30% of the MDREnterobacter strains were resistant to any of the antimicrobial agents tested except meropenem, imipenem and ertapenem and at least 35% of the CRE strains were resistant to any of the antimicrobial agents tested except amikacin and ciprolfoxacin.Conclusions TheEnterobacter isolates in CHINET Antimicrobial Resistance Surveillance Program showed decreasing resistance to most of the antimicrobial agents tested since 2011, but the prevalence of CRE strains increased progressively. Effective measures should be carried out to prevent the spread of CRE strains in hospitals.

Changing resistance proifle ofProteus, Serratia, Citrobacter, Morganella andProvidencia isolates in hospitals across China：data from CHINET Antimicrobial Resistance Surveillance Program 2005-2014 / 中国感染与化疗杂志

Objective To understand the changing resistance proifle ofProteus,Serratia,Citrobacter,Morganella andProvidencia in hospitals across China according to the data from CHINET Antimicrobial Resistance Surveillance Program 2005-2014.Methods Antimicrobial susceptibility was tested by using Kirby-Bauer method or automatic minimum inhibitory concentration determination according to a uniifed protocol.Results A total of 21 663 clinical isolates were collected from January 2005 to December 2014. The proportion ofProteus andSerratia isolates increased with time from 1.41% in 2005 to 2.09% in 2014, and from 0.99% in 2005 to 1.28% in 2014 among all the isolates. No change was found for the proportion ofCitrobacter,Morganella, orProvidencia. Less than 10% of theProteus isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, ceftazidime, cefoxitin, amikacin and tigecycline. Less than 10% of theSerratia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, amikacin and tigecycline. Less than 20% of theCitrobacter isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 10% of theMorganella isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 20% of theProvidencia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, cefoxitin and tigecycline.Conclusions The antibiotic resistance ofProteus,Serratia, Citrobacter,Morganella andProvidencia isolates in hospitals across China is growing during the period from 2005 to 2014. Strengthening infection control and rational antibiotic use are effective to slow the growth of drug resistance.

Resistance profile ofSalmonella isolates in hospital across China：results from CHINET Antimicrobial Resistance Surveillance Program, 2005-2014 / 中国感染与化疗杂志

Objective To investigate the distribution and changing resistance proifle ofSalmonella isolates in hospitals across China during the period from January 2005 to December 2014.Methods Seventeen general hospitals and two children’s hospitals were involved in this program. Antimicrobial susceptibility testing was carried out by means of a unified protocol using Kirby-Bauer method or MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion ofSalmonella isolates increased with time from 0.2% in 2005 to 0.7% in 2014. A total of 3 478Salmonella strains were collected from 19 hospitals. The proportion ofSalmonella typhimurium andSalmonella enteritidis was 27.4% and 24.4%, respectively. During the 10-year period, theSalmonella strains showed highest resistance rate to ampicillin (33.3%-64.8%), but low resistance to cefoperazone-sulbactam (0-5.3%) and ciprofloxacin (2.4%-14.3%).S. typhimurium showed higher resistance rate thanS. typhi,S. paratyphi andS. enteritidis. About 76.8% and 50.5% ofS. typhimurium were resistant to ampicillin and trimethoprim-sulfamethoxazole. The average prevalence of multi-drug resistantSalmonellawas 3.9% in the ten-year period, the highest (7.5%) was in 2005, the lowest (1.5%) in 2013.Conclusions During the period from 2004 to 2015, majority of theSalmonella isolates in hospitals across China wasS. typhimurium andS. enteritidis. Ampicillin and trimethoprim-sulfamethoxazole are no longer appropriate for empirical treatment ofS. typhimurium infection due to high resistance rate.Salmonella isolates are relatively more susceptible to third-generation cephalosporins and quinolones. Ongoing monitoring is necessary to identify multi-drug resistant strains ofSalmonella.