Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was ai...Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood(clams) were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden(8 from poultry and 12 from seafood) and 16 were S. Typhimurium(from seafood). All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones(viz., qnrA, qnrB and qnrS) in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.展开更多
Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.H...Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.展开更多
Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the appl...Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the application of broad-spectrum antibiotics in clinical treatment and reducing the occurrence of nosocomial infection.Methods:Retrospective screening and analysis were conducted on the pathogenic strains of hospitalized patients in our hospital in 2022.Results:A total of 2,769 strains of pathogenic bacteria and 390 strains of MDRO were detected and isolated in our hospital in 2022;the detection rate of MDRO was 14.08%.A total of 516 strains(18.64%)Klebsiella pneumoniae(KP)and 62 strains(12.02%)of carbapenem-resistant Klebsiella pneumoniae(CR-KP)were detected;436 strains(15.75%)of Escherichia coli(ECO)were detected,including 8 strains(1.83%)of CR-ECO;342 strains(12.35%)of Pseudomonas aeruginosa(PA)and 116 strains(33.92%)of CR-PA were detected;there were 194 strains(7.01%)of Acinetobacter baumannii(AB),among which 125 strains(64.43%)were CR-AB;there were 291 strains(10.51%)of Staphylococcus aureus,among which 79 strains(27.15%)of methicillin-resistant Staphylococcus aureus(MRSA)were detected;78 strains(2.82%)of Enterococcus faecalis were detected,and vancomycin-resistant enterococcus(VRE)was not detected.The first five MDROs were CR-AB,CR-PA,MRSA,CR-KP,and CR-ECO.The top five departments with the highest MDRO detection rate in 2022 were the ICU(37.44%),the Pulmonology Department(ward 13;31.03%),the Department of Rehabilitation(ward 5;6.67%),the Department of Neurosurgery(ward 11;4.62%),and the Department of General Surgery(ward 10;3.59 The resistance rate of antibacterial drugs is divided into four levels for early warning:30%to 40%,41%to 50%,51%to 75%,and 75%or more.Conclusion:Our hospital should strengthen the monitoring of antimicrobial resistance warning related to MDRO and the abuse of antimicrobial drugs.Based on the results of drug sensitivity and antimicrobial resistance warning,the use of antibiotics should be standardized in clinical practice to reduce nosocomial infection。展开更多
Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the ...Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.展开更多
Objective:To investigate the antimicrobial resistance patterns and prevalence of integrons in Shigella species isolated from children with diarrhea in southwest Iran.Methods:In this study,1530 stool samples were colle...Objective:To investigate the antimicrobial resistance patterns and prevalence of integrons in Shigella species isolated from children with diarrhea in southwest Iran.Methods:In this study,1530 stool samples were collected from children under 15 years with diarrhea referred to teaching hospitals in Ahvaz and Abadan,southwest Iran.Shigella spp.were identified by standard biochemical tests and PCR.The antibiotic resistance pattern of all Shigella isolates was determined by the disk diffusion method and minimum inhibitory concentration(MIC)by E-test.Results:Of 1530 stool samples,91(5.9%,91/1530)were positive for Shigella spp.the most common Shigella isolates were Shigella flexneri 47(51.6%,47/1530).Antibiotic susceptibility tests showed that the highest antibiotic resistance was related to trimethoprimsulfamethoxazole(87.9%,80/91)and ampicillin(86.8%,79/91).Multiplex PCR results revealed that 56%and 86.9%of Shigella isolates carried integron classⅠand integron classⅡgenes,respectively.None of the isolates included the integron classⅢgene.Conclusions:The high prevalence of multi-drug resistance in Shigella isolates in our area increases the concerns about dissemination of the antibiotic-resistant isolates in this bacterium.展开更多
<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicle...<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicles of transmission of pathogenic <em>Listeria</em> strains to humans. This study evaluates the occurrence of <em>Listeria species</em> in faeces of poultry chicken in Lagos. <strong>Methods:</strong> One hundred and fourteen pooled fresh faecal samples from cage-reared broiler chickens were collected from 12 farms in three rural areas in Lagos State from May to August 2019. All samples were analysed for <em>Listeria</em> species detection according to ISO11290-1 standard and confirmed using PCR assay. Susceptibility testing was performed using the Kirby-Bauer disc diffusion technique. <strong>Results:</strong> Twenty-eight (24.6%) <em>Listeria </em>species were detected from 114 faecal samples. The isolated <em>Listeria</em> species were<em> L. monocytogenes</em> 8 (7.0%), <em>L. ivanovii</em> 9 (7.9%),<em> L. grayi </em>7 (6.1%) and<em> L. innocua</em> 4 (3.5%). There was no significant difference in the frequency of occurrence of <em>Listeria</em> species across the different locations (X<sup>2</sup> = 4.98, p = 0.08). The listeria species were susceptible to Augmentin (96.4%), vancomycin (85.7%) and co-trimoxazole (82.1%), but resistant to ceftazidime (100%), tetracycline (75.0%) and ciprofloxacin (71.4%). <strong>Conclusion:</strong> This study reveals high occurrence of multi-drug resistant <em>Listeria</em> species in faecal samples of poultry chickens in Lagos state which may be an important vector in the contamination of the environment and transmission of antibiotic resistant <em>Listeria</em> species to consumers.展开更多
The study is to identify trends and levels of antibiotic resistance of some common Gram-negative strains over time. The samples were collected from Vietnam Military Hospital 103 between 2014 and 2019. A total of 405 &...The study is to identify trends and levels of antibiotic resistance of some common Gram-negative strains over time. The samples were collected from Vietnam Military Hospital 103 between 2014 and 2019. A total of 405 <i>Acinetobacter baumannii</i>., 528 <i>Pseudomonas aeruginosa</i>, 741 <i>Escherichia coli</i>, and 352 <i>Klebsiella pneumoniae</i> strains were identified and antimicrobial susceptibility was by Vitek system and Etest method. The multi-drug resistance (MDR) was major proportion of four common bacteria. In particular, there is a tendency to shift from MDR to Extended drug resistance (XDR) or possibly Pan drug resistant (pPDR). <i>A. baumannii</i> had the highest level of antibiotic resistance, namely, carbapenem (61.5% - 82.5%) and cephalosporin (72.7% - 88.7%). <i>P. aeruginosa</i> resisted most of commonly antibiotics, ranging from 50% to 70%. <i>E. coli</i> had a high resistance with antibiotics like ampicillin (87.2% - 97.6%) and the 3rd generation cephalosporins (up to 79.6%). <i>K. pneumoniae</i> resisted carbapenem from 14.7% to 44.4%, and other antibiotics with the higher rate of 40%. The collected data will be a prerequisite for further studies on mechanisms and factors related to antibiotic resistant bacteria, in order to find out a rational and effective using strategy of antibiotics.展开更多
Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the ant...Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the antibiotic resistance patterns of Gram-negative bacteria from shellfish. We analyzed a total of 540 shellfish (117 clams, 88 oysters, and 136 periwinkles) samples collected from different vendors at Iko and Douglas Creeks in Akwa Ibom State, South-South Nigeria. Conventional cultural techniques, morphological, biochemical characteristics, and PCR amplification were used to identify the bacterial isolates. Antibiotic susceptibility tests (Kirby-Bauer disk diffusion method) and ESBL phenotype (disk) of the isolates were performed. One hundred and thirty-five (135) Gram-negative bacteria comprising 5 genera and 14 species were detected at a prevalence of: <i>Alcaligenes faecalis</i> <i><b>TRB</b></i>-7 38 (28.2%), <i>Pseudomonas oryzihabitans strain <b>KCB</i>005</b> 16 (11.9%), <i>Paenalcaligenes retgerii strain <b>B</i>5</b> 12 (8.9%) <i>Pseudomonas aeruginosa <b>JB</i>2</b> 10 (7.4%), <i>Providencia stuartii <b>DMC</i>-28b</b> 9 (6.7%), <i>Alcaligenes species <b>TLT</i>151</b> 8 (5.9%), <i>Pseudomonas aeruginosa <b>CIFRI DTSB</i>1</b> 7 (5.2%), <i>Paenalcaligenes species <b>UN</i>24</b> 7 (5.2%), <i>Alcaligenes faecalis <b>BT</i>10</b> 7 (5.2%), <i>Vibrio species strain <b>PrVy</i>108</b> 6 (4.4%), <i>Pseudomonas xiamenensis <b>C</i>10-2</b> 5 (3.7%), <i>Providencia vemicola <b>Bu</i>15_38</b> 4 (2.9%), <i>Pseudomonas anguillisceptica</i> <b>4029</b> 3 (2.2%), and <i>Pseudomonas aeruginosa <b>N</i>15-01092</b> 3 (2.2%). All tested isolates showed various degrees of resistance to the thirteen antimicrobials evaluated. High levels of resistance (100%) to cefepime and imipenem were expressed by all isolates except the <i>Providencia</i> species. For the EBSL indicators, all isolates apart from <i>Alcaligenes</i> species were resistant (100%) to ceftriaxone. All <i>Vibrio</i> species were susceptible to norfloxacin, nalidixic acid, and ceftazidime. The identification of antibiotic resistant Gram-negative bacteria (GNARB) from shellfish in this study highlights the risk of disseminated multi-drug resistance—a serious public health concern.展开更多
<b><span style="font-family:Verdana;">Introduction:</span></b><span style="font-family:""><span style="font-family:Verdana;"> In the last two deca...<b><span style="font-family:Verdana;">Introduction:</span></b><span style="font-family:""><span style="font-family:Verdana;"> In the last two decades, the treatment of enteric infections has been complicated by the emergence of antimicrobial resistant strains. Occurrence of multidrug resistant Extended Spectrum Beta Lactamase (ESBL) producing </span><i><span style="font-family:Verdana;">Enterobactaeraceae</span></i><span style="font-family:Verdana;"> pose</span></span><span style="font-family:Verdana;">s</span><span style="font-family:""><span style="font-family:Verdana;"> the greatest risk to public health by raising morbidity and mortality by six folds in developing countries. The present study aims to determine the antibiotics resistance patterns of selected</span><i><span style="font-family:Verdana;"> Entero</span><span style="font-family:Verdana;">bacteriaceae</span></i><span style="font-family:Verdana;"> isolated from commercial poultry production systems i</span><span style="font-family:Verdana;">n Kiamb</span><span><span style="font-family:Verdana;">u County. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A laboratory based cross-sectional study was co</span></span><span style="font-family:Verdana;">nducted in six purposively selected Sub-Counties of Kiambu County from October 2020, to February 2021. A total of 437 fecal samples were collected from each household. The antibiotic susceptibility testing using disk diffusion method w</span></span><span style="font-family:Verdana;">as</span><span style="font-family:""><span style="font-family:Verdana;"> used against </span><i><span style="font-family:Verdana;">E.</span></i></span><i><span style="font-family:""> </span></i><i><span style="font-family:Verdana;">coli</span></i><span style="font-family:""><span style="font-family:Verdana;">;</span><i><span style="font-family:Verdana;"> Salmonella spps.</span></i><span style="font-family:Verdana;">;</span><i><span style="font-family:Verdana;"> Shigella spps.</span></i><span style="font-family:Verdana;">;</span><i> </i><span style="font-family:Verdana;">and</span><i><span style="font-family:Verdana;"> Klebsiella spps. </span></i><span style="font-family:Verdana;">which were isolated and identified th</span></span><span style="font-family:Verdana;">r</span><span style="font-family:""><span style="font-family:Verdana;">ough standard biochemical. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">Out of 437 fecal and stool samples collected, 591 isolates were recovered with </span><i><span style="font-family:Verdana;">E.</span></i></span><i><span style="font-family:""> </span></i><i><span style="font-family:Verdana;">coli</span></i><span style="font-family:""><span style="font-family:Verdana;"> (48.9%) being the most frequently identified, followed by </span><i><span style="font-family:Verdana;">Shigella spps.</span></i><span style="font-family:Verdana;"> (18.8%), </span><i><span style="font-family:Verdana;">Salmonella spps.</span></i><span style="font-family:Verdana;"> (18.3%), and </span><i><span style="font-family:Verdana;">Klebsiella spps.</span></i><span style="font-family:Verdana;"> (14.0%). The study shows there was high prevalence of multiple resistance among isolates especially to Sulfamethoxazole (79%), Trimethoprim (71%), and Tetracyclines (59%), correspondingly. Additionally, the isolates showed </span></span><span style="font-family:Verdana;">the </span><span style="font-family:""><span style="font-family:Verdana;">highest rate of suscep</span><span style="font-family:Verdana;">tibility against Cefuroxime (94%), Gentamicin (93%), Ceftriaxo</span><span style="font-family:Verdana;">ne (91%), Cefepime (89%), Cefotaxime (85%), Ceftazidime (84%), and Chloramphenicol (77%), respectively. </span><b><span style="font-family:Verdana;">Discussion:</span></b><span style="font-family:Verdana;"> Our study indicates that both fecal and stool materials from commercial poultry and humans can be reservoir of multi-drug resistance enteric’s which can be a potential route</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">of transmission of resistance genes, which pose a great risk to public health of Kiambu Residence.展开更多
Objective:To find a proper method to assess colistin resistance in multidrug resistant Gram negative bacteria(MDR-GNB)on a routine basis in resource limited settings.Methods:Clinical samples were processed.MDR-GNB wer...Objective:To find a proper method to assess colistin resistance in multidrug resistant Gram negative bacteria(MDR-GNB)on a routine basis in resource limited settings.Methods:Clinical samples were processed.MDR-GNB were identified and were examined for colistin resistance by colistin broth elution method,colistin agar method,and colistin disk elution screening method.Broth microdilution method was used the gold standard.Results:A total of 10235 clinical samples were processed,in which 857(8.4%)MDR-GNB were identified.The very significant errors,categorical agreement,major errors,positive predictive values,negative predictive values,specificity and sensitivity of all the phenotypic methods were 5.5%,0%,94.4%,100%,99.6%,100%and 94.4%,respectively for the detection of colistin resistance.The colistin elution screening method was cheap and easy to perform with similar results to broth microdilution method.Conclusions:All the evaluation methods for colistin resistance showed similar results.So the laboratories can choose any method for detection of colistin resistance.However,we recommend colistin disk elution screening method because,it is easy and cheap and can be performed in limited resources.展开更多
Objective:To investigate the epidemic characteristics of multidrug resistant tuberculosis in Hainan,China,to provide basic information and theories for the prevention and control of multidrug resistant tuberculosis.Me...Objective:To investigate the epidemic characteristics of multidrug resistant tuberculosis in Hainan,China,to provide basic information and theories for the prevention and control of multidrug resistant tuberculosis.Methods:A retrospective descriptive epidemiological study was conducted.Data of multidrug resistant tuberculosis in Hainan Island from January 1,2014 to December 31,2019 were collected for statistical analysis.The counting data were described by frequency(percentage),and the measurement data were described by mean±standard deviation.Chi square test was used to compare the differences between different groups.If P<0.05,the difference was statistically significant.Results:From 2014 to 2019,the multidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treated tuberculosis,and 44.2%(306/693)in retreatedmultidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treatedtuberculosis,and 44.2%(306/693)in retreated tuberculosis.The multidrug resistant rate of newly-treated tuberculosis decreased by 0.05%per year,while that of retreated tuberculosis increased by 0.03%per year.multidrug resistant tuberculosis was mainly distributed in the city of Haikou(83 cases),Danzhou(44 cases),Wenchang(42 cases),Wanning(37 cases)and Dongfang(32 cases),accounting for 64.5%of all multidrug resistant tuberculosis.Among 369 multidrug resistant tuberculosis,81.0%were male.The proportion of newly-treated cases was 17.1%(63/369),while the proportion of retreated cases was 82.9%(306/369),which was significantly higher than that of newly-treated cases.The multidrug resistant rate of tuberculosis in different years was different.Conclusion:The drug resistance rate of tuberculosis in Hainan Island is higher than the national average level,which needs attention.The epidemiological characteristics of multidrug resistant tuberculosis with different treatment history were different.展开更多
Bangladesh composes the most polluted air with Dhaka securing the top position. The purpose of the study is the enumeration of the prevalence of pathogenic bacteria in Dhaka city’s air and their antibiotic susceptibi...Bangladesh composes the most polluted air with Dhaka securing the top position. The purpose of the study is the enumeration of the prevalence of pathogenic bacteria in Dhaka city’s air and their antibiotic susceptibility to the common antibiotics. For the sample collection, different selective media was exposed in air where the highest and lowest CFU was 137 and 1 respectively. Pathogens were screened through Hemolysis, DNase and Coagulase test and identified by 16s rRNA sequencing followed by antibiotic susceptibility test. 16s rRNA sequencing revealed that the organisms were <em>Bacillus</em> <em>altitudinis</em> strain 41KF2bT.28, <em>Bacillus licheniformis</em> strain QMA46-2, <em>Bacillus altitudinis</em>, <em>Bacillus pumilis </em>strain BJ-DEBCR-34, <em>Staphylococcus aureus </em>strain TPS3156, <em>Bacillus sp </em>CO16, <em>Pseudomonas sp</em> strain 96LC22 and <em>Shigella dysenteriae</em> strain ATCC 13313. <em>Shigella dysenteriae</em>, <em>Staphylococcus aureus</em> were 81.81% and 54.54% resistant to the antibiotics. Whole-genome sequencing would help to observe mutations in the traits as changes in hemolytic activity were found during pathogenecity tests.展开更多
Objective:To explore the effects of bronchoscopy alveolar lavage in the treatment of severe pneumonia caused by multiple drug bacterial infection.Methods:A total of 84 patients with severe pneumonia infected by multi-...Objective:To explore the effects of bronchoscopy alveolar lavage in the treatment of severe pneumonia caused by multiple drug bacterial infection.Methods:A total of 84 patients with severe pneumonia infected by multi-drug resistant bacteria were randomly selected from Kunming Second People's Hospital,which is our hospital from January 2019 to December 2020 for this research.They were divided into a reference group and a study group using a digital table method,with 42 cases in each group.The reference group was given the routine treatment,the research group performed bronchoscopy alveolar lavage on this basis to observe the curative effect.Results:Before treatment,there was no significant difference in serum factor indexes and blood gas analysis indexes between the two groups of patients,P>0.05.After treatment,the time of fever,cough,moist rales disappearing and infection control time in the study group were shorter than those in the reference group,P<0.05.Serum tumor necrosis factorα(TNF-α),interleukin-6(IL-6)and interleukin-8(IL-8)levels were lower than the reference group,and the arterial partial pressure of oxygen(PO2)and oxygen saturation(SO2)were both lower than the reference group,P<0.05.The effective rate of the treatment in the study group was higher than that in the reference group,P<0.05.Conclusion:Bronchoscopic alveolar lavage treatment can effectively improve the clinical symptoms of patients with severe pneumonia caused by multi-drug resistant bacterial infection,and the effects are significant.展开更多
Objective To observe the effects of bak gene on killing MDR bladder cancer cells and to study its mechanisms. Methods Bak gene was transfected into MDR bladder cancer cells by liposome. The mRNA of bak and bcl-2 were ...Objective To observe the effects of bak gene on killing MDR bladder cancer cells and to study its mechanisms. Methods Bak gene was transfected into MDR bladder cancer cells by liposome. The mRNA of bak and bcl-2 were detected by in situ hybridization. The protein of bak and bcl-2 were detected by SABC immunohistochemistry. The growth rate of human bladder cancer cells was studied by constructing the growth curve, cell apoptosis being observed by flow cytometry, and the outline of cells observed by fluorescence stain. Results The expression of bak mRNA was positive in EJ/bak cells (64% ,P【0.05).Bak protein expression of EJ/bak cells was positive (60 % ) and bcl-2 protein expression was de creased (P【0.05). The growth of MDR bladder cancer cells was significantly inhibited by 32% after bak gene was transfected (P 【 0. 05 ). Apoptosis cells increased significantly. The apoptosis rate was 35 %. Apoptotic bodies can be found in these cells on fluorescence stain. Conclusion Bak gene could inhibit the growth展开更多
Background:Coronavirus disease 2019(COVID-19)has now spread to most countries and regions of the world.Risk factors associated with multi-drug resistant organism(MDRO)infections in patients with COVID-19 have not been...Background:Coronavirus disease 2019(COVID-19)has now spread to most countries and regions of the world.Risk factors associated with multi-drug resistant organism(MDRO)infections in patients with COVID-19 have not been well studied yet.In the present study,we aimed to identify the risk factors associated with the MDRO infections and their impact on in-hospital mortality of COVID-19 patients.Methods:This retrospective cohort study was conducted between December 2019 and April 2020 at two tertiary hospitals in Wuhan,China.Data of cases were collected through electronic medical records system.This study was focused on cases with bacterial culture records.Risk factors and outcomes associated with MDRO infections were analyzed using logistic regression model.Results:Of the 2891 patients,370 patients have bacterial culture results,and MDROs were isolated in 38 patients.Respiratory tract infections(67.3%)were the most common hospital acquired infections.Variables independently associated with MDRO infections were dyspnea at admission(odds ratio(OR)4.74;95%confidence interval(CI)2.06-10.88;P<0.001),intensive care unit(ICU)admission(OR 5.02;95%CI 1.99-12.63;P<0.01),and invasive mechanical ventilation(OR 5.13;95%CI 2.15-12.27;P<0.001),adjusted for age and gender.MDROs infection was also a significant risk factor of death for the patients,adjusted for age,gender,severity of illness,ICU admission and mechanical ventilation(OR 1.12,95%CI:0.43-2.96,P=0.817).Conclusion:In our study,dyspnea at admission,ICU admission and invasive mechanical ventilation were associated with the presence of MDRO infections,and clinicians should be alert in MDRO infections in COVID-19 hospitalized patients.展开更多
<span style="font-family:;" "=""><span style="font-family:Verdana;">Antimicrobial resistance refers to the ability of microorganisms to grow in the presence of an antimic...<span style="font-family:;" "=""><span style="font-family:Verdana;">Antimicrobial resistance refers to the ability of microorganisms to grow in the presence of an antimicrobial agent at a concentration that will normally kill or inhibit their growth. Antimicrobial resistance has become a major global threat making treatment of infections tougher especially with high cost of treatment in humans and animals. This study was done to determine the Multiple Antibiotic Resistant Index (MARI) of Gram-negative bacteria from bird droppings in two commercial poultries in Enugu. Forty (40) samples were collected from each of the poultries. Isolates were identified by standard microbiological methods. The isolates identified were </span><i><span style="font-family:Verdana;">Escherichia</span></i> <i><span style="font-family:Verdana;">coli</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Klebsiella</span></i> <i><span style="font-family:Verdana;">pneumoniae</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Pseudomonas</span></i> <i><span style="font-family:Verdana;">aeruginosa</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Citrobacter</span></i><span style="font-family:Verdana;"> spp, </span><i><span style="font-family:Verdana;">Proteus</span></i><span style="font-family:Verdana;"> spp. and, </span><i><span style="font-family:Verdana;">Enterobacter</span></i><span style="font-family:Verdana;"> spp. Antibiotic susceptibility testing was carried out using disc diffusion technique. The organisms were tested against pefloxacin, augmentin (amoxicillin and clavulanic acid), ceftazidime, streptomycin, ciprofloxacin, gentamycin, cephalothin, neomycin and ofloxacin. The result of the susceptibility test showed that </span><i><span style="font-family:Verdana;">Proteus</span></i><span style="font-family:Verdana;"> spp had the highest resistance and MARI value of 0.5 and</span></span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">1.0 respectively. The other MARI values were </span><i><span style="font-family:Verdana;">Escherichia</span></i> <i><span style="font-family:Verdana;">coli</span></i><span style="font-family:Verdana;"> (0.9), </span><i><span style="font-family:Verdana;">Klebsiella</span></i> <i><span style="font-family:Verdana;">pneumonia</span></i><span style="font-family:Verdana;"> (0.9), </span><i><span style="font-family:Verdana;">Pseudomonas</span></i> <i><span style="font-family:Verdana;">aeruginosa</span></i><span style="font-family:Verdana;"> (0.8), </span><i><span style="font-family:Verdana;">Citrobacter</span></i><span style="font-family:Verdana;"> spp (0.8) and </span><i><span style="font-family:Verdana;">Enterobacter</span></i><span style="font-family:Verdana;"> spp (0.7). These results suggest that bacterial organisms from poultry source can contribute significantly to the spread of multi-antibiotic resistant organisms. This could arise from the indiscriminate use of antibiotics in bird feeds in poultries.</span></span>展开更多
Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to...Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to May 2020 were selected for the study,of which 73 carried drug-resistant bacteria.Results:The risk factor network of people infected with multidrug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria,and the interaction between risk factors of the former is stronger.Conclusion:Antibiotics must be used appropriately after surgery.When the elderly was abnormal in indicators such as fever and procalcitonin in the ward,they should be considered as high-risk groups of MDRO infection.They need special care and preventive measures.展开更多
Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients s...Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients suffered from relapsed/refractory disease and had poor survival outcomes.The detailed mechanism underlying R-CHOP resistance has not been well defined.For this review,we conducted a thorough search for literature and clinical trials involving DLBCL resistance.We discussed DLBCL biology,epigenetics,and aberrant signaling of the B-cell receptor(BCR),phosphatidylinositol 3-kinase(PI3K)/Akt,nuclear factor kappa light chain enhancer of activated B-cells(NF-κB),and the Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance.The cell of origin,double-or triple-hit lymphoma and double-protein-expression,clonal evolution,tumor microenvironment,and multi-drug resistance help to contextualize DLBCL resistance in an(epi)genetically and biologically comparative manner.With better understanding of the biological and molecular landscape of DLBCL,a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.展开更多
Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatme...Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatment.Herein,we report a general method to synthesize pH-dissociable calcium carbonate(CaCO_(3))hollow nanoparticles with amorphous CaCO_(3)as the template,gallic acid(GA)as the organic ligand,and ferrous ions as the metallic center via a one-pot coordination reaction.The obtained GA–Fe@CaCO_(3)exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin,yielding drug loaded GA-Fe@CaCO_(3)nanotherapeutics featured in pH-responsive size shrinkage,drug release,and Fenton catalytic activity.Compared to nonresponsive GA-Fe@silica nanoparticles prepared with silica nanoparticles as the template,such GA-Fe@CaCO_(3)confers significantly improved intratumoral penetration capacity.Moreover,both types of drug-loaded GA–Fe@CaCO_(3)nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate(ATP).As a result,it is found that the doxorubicin loaded GA-Fe@CaCO_(3)exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies.This work highlights the preparation of pH-dissociable CaCO_(3)-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.展开更多
Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised populations.The high mortality of systematic fungal infections necessitates novel antifungal drugs and ...Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised populations.The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies.Unfortunately,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two decades.Drug efflux is one of the major contributors to multi-drug resistance,the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance.In this study,we combined structure-based virtual screening and whole-cell based mechanism study,identified a natural product,beauvericin(BEA)as a drug efflux pump modulator,which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette(ABC)transporters;meantime,BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species(ROS).It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole(KTC)and could cure the murine model of disseminated candidiasis.Toxicity evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-a-go-go-related gene)test promised that BEA can be harnessed for treatment of candidiasis,especially the candidiasis caused by ABC overexpressed multi-drug resistant C.albicans.展开更多
文摘Salmonella enterica has been documented as one of the leading causes of salmonellosis throughout the world and is most commonly associated with the consumption of contaminated food products. Thus, this research was aimed at studying the antimicrobial susceptibility pattern and detection of quinolone resistance in Salmonella spp isolated from food of animal origin. Thirty-six Salmonella isolates comprising 8 from poultry and 28 from seafood(clams) were identified, serotyped and characterized for their antimicrobial susceptibility against 10 different antibiotics. Plasmid DNA was isolated from all the isolates by alkaline lysis, quinolone resistant non-typhoidal S. Weltevreden were examined for mutation in the DNA gyrase coding gene. Among the 36 Salmonella isolates, 20 were S. weltevreden(8 from poultry and 12 from seafood) and 16 were S. Typhimurium(from seafood). All the isolates showed multiple resistance to nalidixic acid, tetracycline, co-trimoxazole and nitrofurantoin, but, interestingly, the isolates were 100% susceptible to ampicillin, chloramphenicol and gentamicin. Resistant isolates from the study carried the genes responsible for resistance to respective antibiotics. The strain S130 isolated in the study showed single point mutation,Asp87Gly, at position 87 in quinolone resistance determining region. It revealed mutation in quinolone resistance determining region as a cause for quinolone resistance in non-typhoidal Salmonellae. The occurrence of genes accountable for plasmid mediated resistance to quinolones(viz., qnrA, qnrB and qnrS) in plasmid of non-typhoidal Salmonellae isolates provides evidence for plasmid mediated quinolone resistance.
基金This study was financially supported by the National Key Research and Development Program of China(2022YFC2804100,2021YFF0502400,2022YFC2804300)National Natural Science Foundation of China(82073713,22137006,82104033,82173730,81903499,32070070,82160669)Innovative research team of highlevel local universities in Shanghai(SHSMU-ZDCX20212702,China).We thank Dr.Juncheng Su from Shanghai Jiao-Tong University School of Medicine(Shanghai,China)for providing the LoVo and COLO 320DM cell lines.
文摘Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.
文摘Objective:To determine the clinical distribution of multi-drug resistant organism(MDRO)in Jiangyan Hospital and the monitoring and warning of drug-resistance bacteria to provide an important basis for guiding the application of broad-spectrum antibiotics in clinical treatment and reducing the occurrence of nosocomial infection.Methods:Retrospective screening and analysis were conducted on the pathogenic strains of hospitalized patients in our hospital in 2022.Results:A total of 2,769 strains of pathogenic bacteria and 390 strains of MDRO were detected and isolated in our hospital in 2022;the detection rate of MDRO was 14.08%.A total of 516 strains(18.64%)Klebsiella pneumoniae(KP)and 62 strains(12.02%)of carbapenem-resistant Klebsiella pneumoniae(CR-KP)were detected;436 strains(15.75%)of Escherichia coli(ECO)were detected,including 8 strains(1.83%)of CR-ECO;342 strains(12.35%)of Pseudomonas aeruginosa(PA)and 116 strains(33.92%)of CR-PA were detected;there were 194 strains(7.01%)of Acinetobacter baumannii(AB),among which 125 strains(64.43%)were CR-AB;there were 291 strains(10.51%)of Staphylococcus aureus,among which 79 strains(27.15%)of methicillin-resistant Staphylococcus aureus(MRSA)were detected;78 strains(2.82%)of Enterococcus faecalis were detected,and vancomycin-resistant enterococcus(VRE)was not detected.The first five MDROs were CR-AB,CR-PA,MRSA,CR-KP,and CR-ECO.The top five departments with the highest MDRO detection rate in 2022 were the ICU(37.44%),the Pulmonology Department(ward 13;31.03%),the Department of Rehabilitation(ward 5;6.67%),the Department of Neurosurgery(ward 11;4.62%),and the Department of General Surgery(ward 10;3.59 The resistance rate of antibacterial drugs is divided into four levels for early warning:30%to 40%,41%to 50%,51%to 75%,and 75%or more.Conclusion:Our hospital should strengthen the monitoring of antimicrobial resistance warning related to MDRO and the abuse of antimicrobial drugs.Based on the results of drug sensitivity and antimicrobial resistance warning,the use of antibiotics should be standardized in clinical practice to reduce nosocomial infection。
文摘Background: Infections in ICU’s patients are known to often originate from the colonization of wounds by the patient’s endogenous microbiota, and to eventually lead to secondary sepsis. Aim: to compare in vitro the direct and residual effects after different exposure times of 4% chlorhexidine, and of 0.1% and 0.04% polyhexanide (in gel and solution forms), on ATCC-microorganisms, and too, on bacterial strains obtained from ICU patients. Methods: We used wild multi-drug resistant strains recently obtained from the wounds of patients hospitalized at ICU and reference strains from the American Type Culture Collection (ATCC). Chlorhexidine 4% was studied as a reference solution. The direct and residual effects of the 0.1% and 0.04% polyhexanide, in gel and solution forms, were analyzed using cotton germ carriers. To evaluate the direct effect, we exposed the strains to the antiseptic. To assess the residual effect, the germ-carriers were impregnated with antiseptic and were allowed to dry before we contaminated them. We inoculated the germ carriers in a culture medium with an inhibitor of antiseptic effect to count the number of surviving microorganisms. Findings: 0.1% Polyhexanide solution proved a direct and residual efficacy after 24 hours equivalent to 4% chlorhexidine. Is very important to highlight that this great efficacy did not change according to whether they were ATCC or multidrug-resistant strains. Conclusions: 0.1% polyhexanide demonstrated a great direct and residual efficacy (like 4% chlorhexidine), against multi-drug resistant strains isolated from ICU’s patients. Moreover, due to its few cytotoxicity against keratinocytes and fibroblasts can be an optimal antiseptic for burns, wounds or ulcers.
基金supported by the Vice-Chancellor for Research grant(Grant No.U98-564)of Abadan University of Medical Science
文摘Objective:To investigate the antimicrobial resistance patterns and prevalence of integrons in Shigella species isolated from children with diarrhea in southwest Iran.Methods:In this study,1530 stool samples were collected from children under 15 years with diarrhea referred to teaching hospitals in Ahvaz and Abadan,southwest Iran.Shigella spp.were identified by standard biochemical tests and PCR.The antibiotic resistance pattern of all Shigella isolates was determined by the disk diffusion method and minimum inhibitory concentration(MIC)by E-test.Results:Of 1530 stool samples,91(5.9%,91/1530)were positive for Shigella spp.the most common Shigella isolates were Shigella flexneri 47(51.6%,47/1530).Antibiotic susceptibility tests showed that the highest antibiotic resistance was related to trimethoprimsulfamethoxazole(87.9%,80/91)and ampicillin(86.8%,79/91).Multiplex PCR results revealed that 56%and 86.9%of Shigella isolates carried integron classⅠand integron classⅡgenes,respectively.None of the isolates included the integron classⅢgene.Conclusions:The high prevalence of multi-drug resistance in Shigella isolates in our area increases the concerns about dissemination of the antibiotic-resistant isolates in this bacterium.
文摘<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicles of transmission of pathogenic <em>Listeria</em> strains to humans. This study evaluates the occurrence of <em>Listeria species</em> in faeces of poultry chicken in Lagos. <strong>Methods:</strong> One hundred and fourteen pooled fresh faecal samples from cage-reared broiler chickens were collected from 12 farms in three rural areas in Lagos State from May to August 2019. All samples were analysed for <em>Listeria</em> species detection according to ISO11290-1 standard and confirmed using PCR assay. Susceptibility testing was performed using the Kirby-Bauer disc diffusion technique. <strong>Results:</strong> Twenty-eight (24.6%) <em>Listeria </em>species were detected from 114 faecal samples. The isolated <em>Listeria</em> species were<em> L. monocytogenes</em> 8 (7.0%), <em>L. ivanovii</em> 9 (7.9%),<em> L. grayi </em>7 (6.1%) and<em> L. innocua</em> 4 (3.5%). There was no significant difference in the frequency of occurrence of <em>Listeria</em> species across the different locations (X<sup>2</sup> = 4.98, p = 0.08). The listeria species were susceptible to Augmentin (96.4%), vancomycin (85.7%) and co-trimoxazole (82.1%), but resistant to ceftazidime (100%), tetracycline (75.0%) and ciprofloxacin (71.4%). <strong>Conclusion:</strong> This study reveals high occurrence of multi-drug resistant <em>Listeria</em> species in faecal samples of poultry chickens in Lagos state which may be an important vector in the contamination of the environment and transmission of antibiotic resistant <em>Listeria</em> species to consumers.
文摘The study is to identify trends and levels of antibiotic resistance of some common Gram-negative strains over time. The samples were collected from Vietnam Military Hospital 103 between 2014 and 2019. A total of 405 <i>Acinetobacter baumannii</i>., 528 <i>Pseudomonas aeruginosa</i>, 741 <i>Escherichia coli</i>, and 352 <i>Klebsiella pneumoniae</i> strains were identified and antimicrobial susceptibility was by Vitek system and Etest method. The multi-drug resistance (MDR) was major proportion of four common bacteria. In particular, there is a tendency to shift from MDR to Extended drug resistance (XDR) or possibly Pan drug resistant (pPDR). <i>A. baumannii</i> had the highest level of antibiotic resistance, namely, carbapenem (61.5% - 82.5%) and cephalosporin (72.7% - 88.7%). <i>P. aeruginosa</i> resisted most of commonly antibiotics, ranging from 50% to 70%. <i>E. coli</i> had a high resistance with antibiotics like ampicillin (87.2% - 97.6%) and the 3rd generation cephalosporins (up to 79.6%). <i>K. pneumoniae</i> resisted carbapenem from 14.7% to 44.4%, and other antibiotics with the higher rate of 40%. The collected data will be a prerequisite for further studies on mechanisms and factors related to antibiotic resistant bacteria, in order to find out a rational and effective using strategy of antibiotics.
文摘Antibiotic resistant bacteria pathogens remain the leading cause of shellfish borne diseases and a major health threat to humans worldwide. The objectives of this study were to isolate, identify, and determine the antibiotic resistance patterns of Gram-negative bacteria from shellfish. We analyzed a total of 540 shellfish (117 clams, 88 oysters, and 136 periwinkles) samples collected from different vendors at Iko and Douglas Creeks in Akwa Ibom State, South-South Nigeria. Conventional cultural techniques, morphological, biochemical characteristics, and PCR amplification were used to identify the bacterial isolates. Antibiotic susceptibility tests (Kirby-Bauer disk diffusion method) and ESBL phenotype (disk) of the isolates were performed. One hundred and thirty-five (135) Gram-negative bacteria comprising 5 genera and 14 species were detected at a prevalence of: <i>Alcaligenes faecalis</i> <i><b>TRB</b></i>-7 38 (28.2%), <i>Pseudomonas oryzihabitans strain <b>KCB</i>005</b> 16 (11.9%), <i>Paenalcaligenes retgerii strain <b>B</i>5</b> 12 (8.9%) <i>Pseudomonas aeruginosa <b>JB</i>2</b> 10 (7.4%), <i>Providencia stuartii <b>DMC</i>-28b</b> 9 (6.7%), <i>Alcaligenes species <b>TLT</i>151</b> 8 (5.9%), <i>Pseudomonas aeruginosa <b>CIFRI DTSB</i>1</b> 7 (5.2%), <i>Paenalcaligenes species <b>UN</i>24</b> 7 (5.2%), <i>Alcaligenes faecalis <b>BT</i>10</b> 7 (5.2%), <i>Vibrio species strain <b>PrVy</i>108</b> 6 (4.4%), <i>Pseudomonas xiamenensis <b>C</i>10-2</b> 5 (3.7%), <i>Providencia vemicola <b>Bu</i>15_38</b> 4 (2.9%), <i>Pseudomonas anguillisceptica</i> <b>4029</b> 3 (2.2%), and <i>Pseudomonas aeruginosa <b>N</i>15-01092</b> 3 (2.2%). All tested isolates showed various degrees of resistance to the thirteen antimicrobials evaluated. High levels of resistance (100%) to cefepime and imipenem were expressed by all isolates except the <i>Providencia</i> species. For the EBSL indicators, all isolates apart from <i>Alcaligenes</i> species were resistant (100%) to ceftriaxone. All <i>Vibrio</i> species were susceptible to norfloxacin, nalidixic acid, and ceftazidime. The identification of antibiotic resistant Gram-negative bacteria (GNARB) from shellfish in this study highlights the risk of disseminated multi-drug resistance—a serious public health concern.
文摘<b><span style="font-family:Verdana;">Introduction:</span></b><span style="font-family:""><span style="font-family:Verdana;"> In the last two decades, the treatment of enteric infections has been complicated by the emergence of antimicrobial resistant strains. Occurrence of multidrug resistant Extended Spectrum Beta Lactamase (ESBL) producing </span><i><span style="font-family:Verdana;">Enterobactaeraceae</span></i><span style="font-family:Verdana;"> pose</span></span><span style="font-family:Verdana;">s</span><span style="font-family:""><span style="font-family:Verdana;"> the greatest risk to public health by raising morbidity and mortality by six folds in developing countries. The present study aims to determine the antibiotics resistance patterns of selected</span><i><span style="font-family:Verdana;"> Entero</span><span style="font-family:Verdana;">bacteriaceae</span></i><span style="font-family:Verdana;"> isolated from commercial poultry production systems i</span><span style="font-family:Verdana;">n Kiamb</span><span><span style="font-family:Verdana;">u County. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> A laboratory based cross-sectional study was co</span></span><span style="font-family:Verdana;">nducted in six purposively selected Sub-Counties of Kiambu County from October 2020, to February 2021. A total of 437 fecal samples were collected from each household. The antibiotic susceptibility testing using disk diffusion method w</span></span><span style="font-family:Verdana;">as</span><span style="font-family:""><span style="font-family:Verdana;"> used against </span><i><span style="font-family:Verdana;">E.</span></i></span><i><span style="font-family:""> </span></i><i><span style="font-family:Verdana;">coli</span></i><span style="font-family:""><span style="font-family:Verdana;">;</span><i><span style="font-family:Verdana;"> Salmonella spps.</span></i><span style="font-family:Verdana;">;</span><i><span style="font-family:Verdana;"> Shigella spps.</span></i><span style="font-family:Verdana;">;</span><i> </i><span style="font-family:Verdana;">and</span><i><span style="font-family:Verdana;"> Klebsiella spps. </span></i><span style="font-family:Verdana;">which were isolated and identified th</span></span><span style="font-family:Verdana;">r</span><span style="font-family:""><span style="font-family:Verdana;">ough standard biochemical. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">Out of 437 fecal and stool samples collected, 591 isolates were recovered with </span><i><span style="font-family:Verdana;">E.</span></i></span><i><span style="font-family:""> </span></i><i><span style="font-family:Verdana;">coli</span></i><span style="font-family:""><span style="font-family:Verdana;"> (48.9%) being the most frequently identified, followed by </span><i><span style="font-family:Verdana;">Shigella spps.</span></i><span style="font-family:Verdana;"> (18.8%), </span><i><span style="font-family:Verdana;">Salmonella spps.</span></i><span style="font-family:Verdana;"> (18.3%), and </span><i><span style="font-family:Verdana;">Klebsiella spps.</span></i><span style="font-family:Verdana;"> (14.0%). The study shows there was high prevalence of multiple resistance among isolates especially to Sulfamethoxazole (79%), Trimethoprim (71%), and Tetracyclines (59%), correspondingly. Additionally, the isolates showed </span></span><span style="font-family:Verdana;">the </span><span style="font-family:""><span style="font-family:Verdana;">highest rate of suscep</span><span style="font-family:Verdana;">tibility against Cefuroxime (94%), Gentamicin (93%), Ceftriaxo</span><span style="font-family:Verdana;">ne (91%), Cefepime (89%), Cefotaxime (85%), Ceftazidime (84%), and Chloramphenicol (77%), respectively. </span><b><span style="font-family:Verdana;">Discussion:</span></b><span style="font-family:Verdana;"> Our study indicates that both fecal and stool materials from commercial poultry and humans can be reservoir of multi-drug resistance enteric’s which can be a potential route</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">of transmission of resistance genes, which pose a great risk to public health of Kiambu Residence.
文摘Objective:To find a proper method to assess colistin resistance in multidrug resistant Gram negative bacteria(MDR-GNB)on a routine basis in resource limited settings.Methods:Clinical samples were processed.MDR-GNB were identified and were examined for colistin resistance by colistin broth elution method,colistin agar method,and colistin disk elution screening method.Broth microdilution method was used the gold standard.Results:A total of 10235 clinical samples were processed,in which 857(8.4%)MDR-GNB were identified.The very significant errors,categorical agreement,major errors,positive predictive values,negative predictive values,specificity and sensitivity of all the phenotypic methods were 5.5%,0%,94.4%,100%,99.6%,100%and 94.4%,respectively for the detection of colistin resistance.The colistin elution screening method was cheap and easy to perform with similar results to broth microdilution method.Conclusions:All the evaluation methods for colistin resistance showed similar results.So the laboratories can choose any method for detection of colistin resistance.However,we recommend colistin disk elution screening method because,it is easy and cheap and can be performed in limited resources.
基金National Science and Technology Major Project(No.2018ZX10101003-001-009)theNational Natural Science Foundation of China(No.81960002,81860002)School of Tropical Medicine and Laboratory Medicine,Hainan Medical University/Research Cultivation Fund(No.1021/XPY180017)。
文摘Objective:To investigate the epidemic characteristics of multidrug resistant tuberculosis in Hainan,China,to provide basic information and theories for the prevention and control of multidrug resistant tuberculosis.Methods:A retrospective descriptive epidemiological study was conducted.Data of multidrug resistant tuberculosis in Hainan Island from January 1,2014 to December 31,2019 were collected for statistical analysis.The counting data were described by frequency(percentage),and the measurement data were described by mean±standard deviation.Chi square test was used to compare the differences between different groups.If P<0.05,the difference was statistically significant.Results:From 2014 to 2019,the multidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treated tuberculosis,and 44.2%(306/693)in retreatedmultidrug resistant rate of tuberculosis in Hainan Island was 24.9%(369/1484),8.0%(63/791)in newly-treatedtuberculosis,and 44.2%(306/693)in retreated tuberculosis.The multidrug resistant rate of newly-treated tuberculosis decreased by 0.05%per year,while that of retreated tuberculosis increased by 0.03%per year.multidrug resistant tuberculosis was mainly distributed in the city of Haikou(83 cases),Danzhou(44 cases),Wenchang(42 cases),Wanning(37 cases)and Dongfang(32 cases),accounting for 64.5%of all multidrug resistant tuberculosis.Among 369 multidrug resistant tuberculosis,81.0%were male.The proportion of newly-treated cases was 17.1%(63/369),while the proportion of retreated cases was 82.9%(306/369),which was significantly higher than that of newly-treated cases.The multidrug resistant rate of tuberculosis in different years was different.Conclusion:The drug resistance rate of tuberculosis in Hainan Island is higher than the national average level,which needs attention.The epidemiological characteristics of multidrug resistant tuberculosis with different treatment history were different.
文摘Bangladesh composes the most polluted air with Dhaka securing the top position. The purpose of the study is the enumeration of the prevalence of pathogenic bacteria in Dhaka city’s air and their antibiotic susceptibility to the common antibiotics. For the sample collection, different selective media was exposed in air where the highest and lowest CFU was 137 and 1 respectively. Pathogens were screened through Hemolysis, DNase and Coagulase test and identified by 16s rRNA sequencing followed by antibiotic susceptibility test. 16s rRNA sequencing revealed that the organisms were <em>Bacillus</em> <em>altitudinis</em> strain 41KF2bT.28, <em>Bacillus licheniformis</em> strain QMA46-2, <em>Bacillus altitudinis</em>, <em>Bacillus pumilis </em>strain BJ-DEBCR-34, <em>Staphylococcus aureus </em>strain TPS3156, <em>Bacillus sp </em>CO16, <em>Pseudomonas sp</em> strain 96LC22 and <em>Shigella dysenteriae</em> strain ATCC 13313. <em>Shigella dysenteriae</em>, <em>Staphylococcus aureus</em> were 81.81% and 54.54% resistant to the antibiotics. Whole-genome sequencing would help to observe mutations in the traits as changes in hemolytic activity were found during pathogenecity tests.
基金Fund project no.:2020-SW(reserved)-52Kunming Health Commission 1000 project reserved candidates:Study on the diagnostic value of BALF solution acer sequencing and culturing in difficult and severe respiratory infections.
文摘Objective:To explore the effects of bronchoscopy alveolar lavage in the treatment of severe pneumonia caused by multiple drug bacterial infection.Methods:A total of 84 patients with severe pneumonia infected by multi-drug resistant bacteria were randomly selected from Kunming Second People's Hospital,which is our hospital from January 2019 to December 2020 for this research.They were divided into a reference group and a study group using a digital table method,with 42 cases in each group.The reference group was given the routine treatment,the research group performed bronchoscopy alveolar lavage on this basis to observe the curative effect.Results:Before treatment,there was no significant difference in serum factor indexes and blood gas analysis indexes between the two groups of patients,P>0.05.After treatment,the time of fever,cough,moist rales disappearing and infection control time in the study group were shorter than those in the reference group,P<0.05.Serum tumor necrosis factorα(TNF-α),interleukin-6(IL-6)and interleukin-8(IL-8)levels were lower than the reference group,and the arterial partial pressure of oxygen(PO2)and oxygen saturation(SO2)were both lower than the reference group,P<0.05.The effective rate of the treatment in the study group was higher than that in the reference group,P<0.05.Conclusion:Bronchoscopic alveolar lavage treatment can effectively improve the clinical symptoms of patients with severe pneumonia caused by multi-drug resistant bacterial infection,and the effects are significant.
文摘Objective To observe the effects of bak gene on killing MDR bladder cancer cells and to study its mechanisms. Methods Bak gene was transfected into MDR bladder cancer cells by liposome. The mRNA of bak and bcl-2 were detected by in situ hybridization. The protein of bak and bcl-2 were detected by SABC immunohistochemistry. The growth rate of human bladder cancer cells was studied by constructing the growth curve, cell apoptosis being observed by flow cytometry, and the outline of cells observed by fluorescence stain. Results The expression of bak mRNA was positive in EJ/bak cells (64% ,P【0.05).Bak protein expression of EJ/bak cells was positive (60 % ) and bcl-2 protein expression was de creased (P【0.05). The growth of MDR bladder cancer cells was significantly inhibited by 32% after bak gene was transfected (P 【 0. 05 ). Apoptosis cells increased significantly. The apoptosis rate was 35 %. Apoptotic bodies can be found in these cells on fluorescence stain. Conclusion Bak gene could inhibit the growth
基金supported by Clinical Toxicology Grants from Chinese Society of Toxicology(No.CST2020CT604).
文摘Background:Coronavirus disease 2019(COVID-19)has now spread to most countries and regions of the world.Risk factors associated with multi-drug resistant organism(MDRO)infections in patients with COVID-19 have not been well studied yet.In the present study,we aimed to identify the risk factors associated with the MDRO infections and their impact on in-hospital mortality of COVID-19 patients.Methods:This retrospective cohort study was conducted between December 2019 and April 2020 at two tertiary hospitals in Wuhan,China.Data of cases were collected through electronic medical records system.This study was focused on cases with bacterial culture records.Risk factors and outcomes associated with MDRO infections were analyzed using logistic regression model.Results:Of the 2891 patients,370 patients have bacterial culture results,and MDROs were isolated in 38 patients.Respiratory tract infections(67.3%)were the most common hospital acquired infections.Variables independently associated with MDRO infections were dyspnea at admission(odds ratio(OR)4.74;95%confidence interval(CI)2.06-10.88;P<0.001),intensive care unit(ICU)admission(OR 5.02;95%CI 1.99-12.63;P<0.01),and invasive mechanical ventilation(OR 5.13;95%CI 2.15-12.27;P<0.001),adjusted for age and gender.MDROs infection was also a significant risk factor of death for the patients,adjusted for age,gender,severity of illness,ICU admission and mechanical ventilation(OR 1.12,95%CI:0.43-2.96,P=0.817).Conclusion:In our study,dyspnea at admission,ICU admission and invasive mechanical ventilation were associated with the presence of MDRO infections,and clinicians should be alert in MDRO infections in COVID-19 hospitalized patients.
文摘<span style="font-family:;" "=""><span style="font-family:Verdana;">Antimicrobial resistance refers to the ability of microorganisms to grow in the presence of an antimicrobial agent at a concentration that will normally kill or inhibit their growth. Antimicrobial resistance has become a major global threat making treatment of infections tougher especially with high cost of treatment in humans and animals. This study was done to determine the Multiple Antibiotic Resistant Index (MARI) of Gram-negative bacteria from bird droppings in two commercial poultries in Enugu. Forty (40) samples were collected from each of the poultries. Isolates were identified by standard microbiological methods. The isolates identified were </span><i><span style="font-family:Verdana;">Escherichia</span></i> <i><span style="font-family:Verdana;">coli</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Klebsiella</span></i> <i><span style="font-family:Verdana;">pneumoniae</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Pseudomonas</span></i> <i><span style="font-family:Verdana;">aeruginosa</span></i><span style="font-family:Verdana;">, </span><i><span style="font-family:Verdana;">Citrobacter</span></i><span style="font-family:Verdana;"> spp, </span><i><span style="font-family:Verdana;">Proteus</span></i><span style="font-family:Verdana;"> spp. and, </span><i><span style="font-family:Verdana;">Enterobacter</span></i><span style="font-family:Verdana;"> spp. Antibiotic susceptibility testing was carried out using disc diffusion technique. The organisms were tested against pefloxacin, augmentin (amoxicillin and clavulanic acid), ceftazidime, streptomycin, ciprofloxacin, gentamycin, cephalothin, neomycin and ofloxacin. The result of the susceptibility test showed that </span><i><span style="font-family:Verdana;">Proteus</span></i><span style="font-family:Verdana;"> spp had the highest resistance and MARI value of 0.5 and</span></span><span style="font-family:;" "=""> </span><span style="font-family:;" "=""><span style="font-family:Verdana;">1.0 respectively. The other MARI values were </span><i><span style="font-family:Verdana;">Escherichia</span></i> <i><span style="font-family:Verdana;">coli</span></i><span style="font-family:Verdana;"> (0.9), </span><i><span style="font-family:Verdana;">Klebsiella</span></i> <i><span style="font-family:Verdana;">pneumonia</span></i><span style="font-family:Verdana;"> (0.9), </span><i><span style="font-family:Verdana;">Pseudomonas</span></i> <i><span style="font-family:Verdana;">aeruginosa</span></i><span style="font-family:Verdana;"> (0.8), </span><i><span style="font-family:Verdana;">Citrobacter</span></i><span style="font-family:Verdana;"> spp (0.8) and </span><i><span style="font-family:Verdana;">Enterobacter</span></i><span style="font-family:Verdana;"> spp (0.7). These results suggest that bacterial organisms from poultry source can contribute significantly to the spread of multi-antibiotic resistant organisms. This could arise from the indiscriminate use of antibiotics in bird feeds in poultries.</span></span>
文摘Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to May 2020 were selected for the study,of which 73 carried drug-resistant bacteria.Results:The risk factor network of people infected with multidrug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria,and the interaction between risk factors of the former is stronger.Conclusion:Antibiotics must be used appropriately after surgery.When the elderly was abnormal in indicators such as fever and procalcitonin in the ward,they should be considered as high-risk groups of MDRO infection.They need special care and preventive measures.
文摘Although the first-line rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone regimen(R-CHOP)substantially improved outcomes for patients with diffuse large B-cell lymphoma(DLBCL),40%of the patients suffered from relapsed/refractory disease and had poor survival outcomes.The detailed mechanism underlying R-CHOP resistance has not been well defined.For this review,we conducted a thorough search for literature and clinical trials involving DLBCL resistance.We discussed DLBCL biology,epigenetics,and aberrant signaling of the B-cell receptor(BCR),phosphatidylinositol 3-kinase(PI3K)/Akt,nuclear factor kappa light chain enhancer of activated B-cells(NF-κB),and the Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathways as defining mechanisms of DLBCL heterogeneity and R-CHOP resistance.The cell of origin,double-or triple-hit lymphoma and double-protein-expression,clonal evolution,tumor microenvironment,and multi-drug resistance help to contextualize DLBCL resistance in an(epi)genetically and biologically comparative manner.With better understanding of the biological and molecular landscape of DLBCL,a more detailed classification system and tailored treatments will ideally become available to further improve the prognosis of DLBCL patients.
基金supported by the National Natural Science Foundation of China(No.51802209),the National Research Programs from Ministry of Science and Technology(MOST)of China(No.2016YFA0201200)the Natural Science Foundation of Jiangsu Province(No.BK20180848)+1 种基金the China Postdoctoral Science Foundation(No.2018T110545)the Collaborative Innovation Center of Suzhou Nano Science and Technology,and the 111 Program from the Ministry of Education of China.
文摘Construction of multifunctional stimuli-responsive nanotherapeutics enabling improved intratumoral penetration of therapeutics and reversal of multiple-drug resistance(MDR)is potent to achieve effective cancer treatment.Herein,we report a general method to synthesize pH-dissociable calcium carbonate(CaCO_(3))hollow nanoparticles with amorphous CaCO_(3)as the template,gallic acid(GA)as the organic ligand,and ferrous ions as the metallic center via a one-pot coordination reaction.The obtained GA–Fe@CaCO_(3)exhibits high loading efficiencies to both oxidized cisplatin prodrug and doxorubicin,yielding drug loaded GA-Fe@CaCO_(3)nanotherapeutics featured in pH-responsive size shrinkage,drug release,and Fenton catalytic activity.Compared to nonresponsive GA-Fe@silica nanoparticles prepared with silica nanoparticles as the template,such GA-Fe@CaCO_(3)confers significantly improved intratumoral penetration capacity.Moreover,both types of drug-loaded GA–Fe@CaCO_(3)nanotherapeutics exhibit synergistic therapeutic efficacies to corresponding MDR cancer cells because of the GA–Fe mediated intracellular oxidative stress amplification that could reduce the efflux of engulfed drugs by impairing the mitochondrial-mediated production of adenosine triphosphate(ATP).As a result,it is found that the doxorubicin loaded GA-Fe@CaCO_(3)exhibits superior therapeutic effect towards doxorubicin-resistant 4T1 breast tumors via combined chemodynamic and chemo-therapies.This work highlights the preparation of pH-dissociable CaCO_(3)-based nanotherapeutics to enable effective tumor penetration for enhanced treatment of drug-resistant tumors.
基金the National Program on Key Basic Research Project(973program,2013CB734000)in part by grants from the National Natural Science Foundation of China[31670052,31430002,31320103911,31400090,81302678 and 31125002]+2 种基金the Ministry of Science and Tech-nology of the People’s Republic of China[2011ZX09102-011-11,2013ZX10005004-005]China Ocean Mineral Resources R&D Association(Grant No.DY125-15-T-07)the European Union’s Seventh Framework Programme(FP7/2007-2013)under grant agreement no.312184.
文摘Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,particularly to immunocompromised populations.The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies.Unfortunately,with traditional drug discovery approaches,only echinocandins was approved by FDA as a new class of antifungals in the past two decades.Drug efflux is one of the major contributors to multi-drug resistance,the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance.In this study,we combined structure-based virtual screening and whole-cell based mechanism study,identified a natural product,beauvericin(BEA)as a drug efflux pump modulator,which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette(ABC)transporters;meantime,BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species(ROS).It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole(KTC)and could cure the murine model of disseminated candidiasis.Toxicity evaluation of BEA,including acute toxicity test,Ames test,and hERG(human ether-a-go-go-related gene)test promised that BEA can be harnessed for treatment of candidiasis,especially the candidiasis caused by ABC overexpressed multi-drug resistant C.albicans.
