Extracellular vesicles in anti-tumor drug resistance: Mechanisms and therapeutic prospects

Drug resistance presents a significant challenge to achieving positive clinical outcomes in anti-tumor therapy.Prior research has illuminated reasons behind drug resistance,including increased drug efflux,alterations in drug targets,and abnormal activation of oncogenic pathways.However,there's a need for deeper investigation into the impact of drug-resistant cells on parental tumor cells and intricate crosstalk between tumor cells and the malignant tumor microenvironment(TME).Recent studies on extracellular vesicles(EVs)have provided valuable insights.EVs are membrane-bound particles secreted by all cells,mediating cell-to-cell communication.They contain functional cargoes like DNA,RNA,lipids,proteins,and metabolites from mother cells,delivered to other cells.Notably,EVs are increasingly recognized as regulators in the resistance to anti-cancer drugs.This review aims to summarize the mechanisms of EV-mediated anti-tumor drug resistance,covering therapeutic approaches like chemo-therapy,targeted therapy,immunotherapy and even radiotherapy.Detecting Ev-based biomarkers to predict drug resistance assists in bypassing anti-tumor drug resistance.Additionally,targeted inhibition of EV biogenesis and secretion emerges as a promising approach to counter drug resistance.We highlight the importance of conducting in-depth mechanistic research on EVs,their cargoes,and functional ap-proaches specifically focusing on EV subpopulations.These efforts will significantly advance the devel-opment of strategies to overcome drug resistance in anti-tumor therapy.

Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Distribution and drug resistance of pathogens in burn patients in China from 2006 to 2019

BACKGROUND In this study,recent trends in the distribution and drug resistance of pathogenic bacteria isolated from patients treated at a burn ward between 2006 and 2019 were investigated.AIM To develop more effective clinical strategies and techniques for the prevention and treatment of bacterial infections in burn patients.METHODS Clinical samples with positive bacteria were collected from patients at the burn ward in Beijing Jishuitan Hospital in China between January 2006 and December 2019.The samples were retrospectively analyzed,the distribution of pathogenic bacteria was determined,and the trends and changes in bacterial drug resistance during different period were assessed.Drug resistance in several main pathogenic bacteria from 2006 to 2011 and from 2012 to 2019 was comparatively summarized and analyzed.RESULTS Samples from 17119 patients were collected and analyzed from 2006 to 2019.Surprisingly,a total of 7960 strains of different pathogenic bacteria were isolated at this hospital.Among these bacteria,87.98%(7003/7960)of the strains were isolated from burn wounds,and only 1.34%(107/7960)were isolated from the blood of patients.In addition,49.70%(3956/7960)were identified as Grampositive bacteria,48.13%(3831/7960)were Gram-negative bacteria,and the remaining 2.17%(173/7960)were classified as fungi or other pathogens.Importantly,Staphylococcus aureus(21.68%),Pseudomonas aeruginosa(14.23%),and Staphylococcus epidermidis (9.61%) were the top three pathogens most frequentlyisolated from patients.CONCLUSION In patients treated at the burn ward in this hospital from 2006 to 2019,Staphylococcus aureus and Pseudomonas aeruginosa were the predominant clinicalpathogens responsible for bacterial infections. The circumstantial detection anddetailed monitoring of the intensity and growth of different pathogenic bacteria inclinical patients as well as tests of drug sensitivity during burn recovery areparticularly important to provide guidelines for the application of antibiotics andother related drugs. Careful collection and correct, standard culture of bacterialspecimens are also crucial to improve the efficiency of bacterial infectiondetection. Effective monitoring and timely clinical treatment in patients may helpreduce the possibility and rate of infection as well as alleviate the effects of drugresistance among patients in burn centers.

Drug resistance of infectious pathogens after liver transplantation

BACKGROUND: Infection in liver recipients is related to high risk of transplantation failure and mortality. Infectious agents isolated from 55 liver recipients from January 2003 through June 2005 were studied to improve the anti-infectious therapy. METHODS: Pathogens were isolated from routine culture. K-B method was used to examine the drug susceptibility. Extended spectrum β-lactamase, AmpC β-lactamase and Van gene in E. coli were examined by the agar-dilution susceptibility test and Nitrocefin test. RESULTS: Thirty-nine of the 55 recipients got infection. The 513 strains of pathogens isolated from 1861 specimens were predominantly Gram negative bacteria and over 40% of them showed resistance to more than 4 drugs. The positive rates of extended spectrum β-lactamse and AmpC β-lactamse production in E. cloacae were 32.4% and 36.8%, in E. coli were 33.8% and 10.5%, but the rates of these 2 bacteria producing both lactamses were 24.3% and 7.0%. The β-lactamse production rates of Enterococcus faecalis and En-terococcus faecium were 8.8% and 11.1%, and the resistance rates to vancomycin were 11.2% and 18.5%, respectively. CONCLUSIONS: Infectious pathogens isolated from liver recipients are potent and multiple drug resistant. ESBLs and AmpC β-lactamases are the major factors associated with Gram negative drug resistance. The infection of En-terococcal species presents as a particular challenge.

MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1

Objective Retinoblastoma(RB)is a prevalent type of eye cancer in youngsters.Prospero homeobox 1(Prox1)is a homeobox transcriptional repressor and downstream target of the proneural gene that is relevant in lymphatic,hepatocyte,pancreatic,heart,lens,retinal,and cancer cells.The goal of this study was to investigate the role of Prox1 in RB cell proliferation and drug resistance,as well as to explore the underlying Notch1 mechanism.Methods Human RB cell lines(SO-RB50 and Y79)and a primary human retinal microvascular endothelial cell line(ACBRI-181)were used in this study.The expression of Prox1 and Notch1 mRNA and protein in RB cells was detected using quantitative real time-polymerase chain reaction(RT-qPCR)and Western blotting.Cell proliferation was assessed after Prox1 overexpression using the Cell Counting Kit-8 and the MTS assay.Drug-resistant cell lines(SO-RB50/vincristine)were generated and treated with Prox1 to investigate the role of Prox1 in drug resistance.We employed pcDNA-Notch1 to overexpress Notch1 to confirm the role of Notch1 in the protective function of Prox1.Finally,a xenograft model was constructed to assess the effect of Prox1 on RB in vivo.Results Prox1 was significantly downregulated in RB cells.Overexpression of Prox1 effectively decreased RB cell growth while increasing the sensitivity of drug-resistant cells to vincristine.Notch1 was involved in Prox1’s regulatory effects.Notch1 was identified as a target gene of Prox1,which was found to be upregulated in RB cells and repressed by increased Prox1 expression.When pcDNA-Notch1 was transfected,the effect of Prox1 overexpression on RB was removed.Furthermore,by downregulating Notch1,Prox1 overexpression slowed tumor development and increased vincristine sensitivity in vivo.Conclusion These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1,implying that Prox1 could be a potential therapeutic target for RB.

Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

Research progress in tumor angiogenesis and drug resistance in breast cancer

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from tumor angiogenesis plays a critical role in the development of resistance to breast cancer treatments, via exacerbation of tumor hypoxia, decreased effective drug concentrations within tumors, and immune-related mechanisms. Antiangiogenic therapy can counteract these breast cancer resistance factors by promoting tumor vascular normalization. The combination of antiangiogenic therapy with chemotherapy, targeted therapy, or immunotherapy has emerged as a promising approach for overcoming drug resistance in breast cancer. This review examines the mechanisms associated with angiogenesis and the interactions among tumor angiogenesis, the hypoxic tumor microenvironment, drug distribution, and immune mechanisms in breast cancer. Furthermore, this review provides a comprehensive summary of specific antiangiogenic drugs, and relevant studies assessing the reversal of drug resistance in breast cancer. The potential mechanisms underlying these interventions are discussed, and prospects for the clinical application of antiangiogenic therapy to overcome breast cancer treatment resistance are highlighted.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Analysis of The Correlation Between inhA Gene Mutation and Resistance to Protionamide in Drug-Resistant Mycobacterium Tuberculosis

Objective: To investigate the characteristics of katG and inhA gene mutations in multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant tuberculosis (preXDR-TB), and their correlation with resistance to protionamide (Pto). Methods: A total of 229 patients with MDR-TB and pre-XDR-TB diagnosed in the Eighth Affiliated Hospital of Xinjiang Medical University from January 2020 to February 2024 were selected to analyze the characteristics of katG and inhA mutations in MTB clinical isolates and their correlation with Pto resistance. Results: The mutation rate of katG (with or without inhA mutation) was 85.2%. The mutation rates in MDR-TB and pre-XDR-TB were 87.4% (125/143) and 81.4% (70/86), respectively. The mutation rate of inhA (including katG mutation) was 14.8% (34/229), which was 12.6% (18/143) and 18.6% (16/86) in MDR-TB and pre-XDR-MTB, respectively. There was no difference in mutation (P > 0.05). Conclusion: The total resistance rate to Pto in 229 strains was 8.7% (20/229), which was 8.4% (12/143) and 9.3% (8/86) in MDR-TB and pre-XDR-TB, respectively. Among the inhA mutant strains, 13 were resistant to the Pto phenotype, and the resistance rate was 65% (13/20). In MDR-TB and pre-XDR-TB strains resistant to Pto, inhA gene mutations occurred in 66.7% (6/9) and 63.6% (7/11), respectively. The resistance rates of MDR-MTB and pre-XDR-TB strains without inhA gene mutation to Pto were 2.4% (3/125) and 5.7% (4/70), respectively.

Utilizing metabolomic approach to study the mode of action of fungicides and corresponding resistance in plant pathogens

Fungicides are an indispensable tool in plant disease control.Various modes of action(MOAs)have been identified in different fungicides to suppress plant pathogens.The combined use of fungicides with distinct MOAs has been recommended to prevent the development of pathogen resistance.In studying MOAs,metabolomics has been proven to be a robust and high-throughput method.Because metabolites are unique and distinct depending on the biological activities of an organism,MOAs can be identified and classified by establishing metabolic fingerprinting and metabolic profiles.Similarly,if fungicide resistance is developed in a pathogen,the metabolome will change,which can be identified.In this review,we have discussed the principles and advanced applications of metabolomics in the study of MOAs and resistance mechanisms of fungicides,and the potential of metabolic data in understanding the interaction between fungicides and pathogens.Challenges are also discussed in the application of metabolomics,improvement of the study on the mechanism of fungicides in their functions against pathogens and advancing the development of novel fungicides.

Three-in-one DNA nanowheels for simultaneous tumor regression and drug resistance prevention in breast cancer model

Herein,we proposed novel three-in-one DNA nanowheels with simultaneous chemo and gene therapy to treat tumor,especially to prevent simultaneous drug resistance,which could be disassembled via a cascaded hybridization reactions triggered by the highly expressed microRNA in cancer cells for smart and efficient cancer therapy.Typically,with breast cancer as a model,microRNA 21 could trigger the self-disassembly of DNA nanowheel 1 via hybridization with a specially designed oligonucleotide(anti-microRNA 21)in DNA nanowheel 1,releasing another special oligonucleotide(Contact sequence)to trigger the self-disassembly of DNA nanowheel 2 with releasing of a special oligonucleotide(anti-Contact sequence)to trigger the self-disassembly of DNA nanowheel 1 cyclically,and thus the cascaded hybridization reactions with three-in-one anti-cancer functions could be generated based on three main therapeutic effects via releasing doxorubicin to inhibit macromolecular biosynthesis,antisense oligonucleotide of microRNA 21 to activate the apoptotic cell pathway and antisense oligonucleotide of MDR1 to prevent the drug resistance respectively.As expected,the proposed method showed improved therapeutic efficacy on the cancer cells with about 80%apoptosis ratio,especially on the drug resistant cancer cells with about 75%apoptosis ratio,compared with that in the conventional anti-cancer systems of about 70%on cancer cells and below 40%on drug resistant cancer cells,respectively.Most importantly,this strategy opened the door for generation of complex functional DNA-based structures for target triggering drugs releasing system combining with chemo-and genetherapy to generate tumor regression and prevent drug resistance with an optimized therapeutic efficacy,providing a new avenue for efficient cancer treatment,especially drug resistant cancers.

Prevalence and Antibiotic Profile of Multidrug Resistance Gram-Negative Pathogens Isolated from Wound Infections at Two Tertiary Hospitals in Limpopo Province, South Africa: A Retrospective Study

Background: There is a high mortality and morbidity associated with multidrug resistance pathogens. The high rate of MDR isolates is gradually becoming a threat to the coverage of antibiotics including the clinical outcome of infected patients. Methods: A 5-year laboratory based antibiotic susceptibility data from January 2016 to December 2020 was reviewed to determine the most prevalent MDR pathogens isolated from samples taken from patients with wound infections at Pietersburg and Mankweng Hospitals. Results: A total of 792 pathogens were analyzed. The most prevalent isolates were Klebsiella pneumoniae (23%), Pseudomonas aeruginosa (21.7%), Escherichia coli (16%), Proteus mirabilis (13.5%), Acinetobacter baumannii (9.1%) and Klebsiella oxytoca (3.8%). The overall prevalence of MDR isolates in this study was 38.1%. The distribution of MDR prevalence amongst these isolates was K. pneumoniae (20.8%), P. aeruginosa (18.8%), P. mirabilis (17.5%), E. coli (15.9%) and A. baumannii (8.3%). Of the 9 antibiotic agents tested, trimethoprim sulfamethoxazole, tigecycline and cefepime had the highest levels of resistance. The highest level of resistance was conferred by K. pneumoniae having 63% of isolates identified as MDR. The study could not determine statistical significance of any determinant of MDR. Conclusion: The study revealed that there is high rate of MDR pathogens (38.9%) in Limpopo. Majority of the pathogens were K. pneumoniae from surgical ward, which also conferred high resistance levels. A proportion of the MDR pathogens was identified as A. baumannii CRE pathogens and is noteworthy in implementation aggressive infection prevention and control strategies.

Microbial spectrum and drug resistance of pathogens cultured from gallbladder bile specimens of patients with cholelithiasis:A singlecenter retrospective study

BACKGROUND Bacterial infection is an important cause of cholelithiasis or gallstones and interferes with its treatment.There is no consensus on bile microbial culture profiles in previous studies,and identified microbial spectrum and drug resistance is helpful for targeted preventive and therapeutic drugs in the perioperative period.AIM To analyze the bile microbial spectrum of patients with cholelithiasis and the drug susceptibility patterns in order to establish an empirical antibiotic treatment for cholelithiasis-associated infection.METHODS A retrospective single-center study was conducted on patients diagnosed with cholelithiasis between May 2013 and December 2018.RESULTS This study included 185 patients,of whom 163(88.1%)were diagnosed with gallstones and 22(11.9%)were diagnosed with gallstones and common bile duct stones(CBDSs).Bile culture in 38 cases(20.5%)was positive.The presence of CBDSs(OR=5.4,95%CI:1.3-21.9,P=0.03)and longer operation time(>80 min)(OR=4.3,95%CI:1.4-13.1,P=0.01)were identified as independent risk factors for positive bile culture.Gram-negative bacteria were detected in 28 positive bile specimens,and Escherichia coli(E.coli)(19/28)and Klebsiella pneumoniae(5/28)were the most frequently identified species.Gram-positive bacteria were present in 10 specimens.The resistance rate to cephalosporin in E.coli was above 42%and varied across generations.All the isolated E.coli strains were sensitive to carbapenems,with the exception of one imipenem-resistant strain.K.pneumoniae showed a similar resistance spectrum to E.coli.Enterococcus spp.was largely sensitive to glycopeptides and penicillin,except for a few strains of E.faecium.CONCLUSION The presence of common bile duct stones and longer operation time were identified as independent risk factors for positive bile culture in patients with cholelithiasis.The most commonly detected bacterium was E.coli.The combination ofβ-lactam antibiotics andβ-lactamase inhibitors prescribed perioperatively appears to be effective against bile pathogens and is recommended.Additionally,regular monitoring of emerging resistance patterns is required in the future.

Distribution and drug resistance of pathogens isolated from 4142 blood cultures

Objective:To investigate the distribution and drug resistance of pathogens isolated from 4142 blood cultures, and provide a scientific foundation for guiding clinical rational use of antimicrobial agents for bloodstream infections.Methods: Blood cultures obtained from 4142 inpatients and outpatients who were hospitalized from Jan 2015 to Dec 2016. The culture was detected by automatic BACT/ALERT 3D blood culture system of biomerieux. Bacteria isolated from positive blood cultures were further identified, and the drug susceptibility tests were conducted by VITEK-2 Compact automatic microbial analysis system and ATB Expression microbial analysis system. The drug susceptibility results were evaluated according to CLSI 2014 standard. Statistical analysis was performed by using WHONET 5.6 software. Results:A total of 396 unique strains were isolated from 4142 blood cultures, and the positive rate is 9.6%. Among the positive blood cultures, 194 (49.0%) strains were identified as Gram-positive, 185 (46.7%) strains were identified as Gram-negative, and 17(4.3%) strains were identified as fungi. The coagulase-negative Staphylococcus were the most frequently detectable (29.2%), followed by Escherichia coli (18.4%), Klebsiella pneumonia (7.3%), Staphylococcus aureus (5.1%), Acinetobacter baumannii(5.1%), and Enterococcus genera (5.1%). The incidences of methicillin resistant coagulase negative staphylococcus (MRCNS) and methicillin resistant staphylococcus aureus (MRSA) were 81.9% and 50.0% respectively. However, vancomycin resistant staphylococcus and enterococcus were not detected. The prevalence of extended spectrumβ lactamases (ESBLs) in E. coli and K. pneumoniae were 56.2% and 37.9%, respectively. All the E. coli strains were sensitive to amikacin, piperacillin/tazobactam, imipenem and meropenem, and the sensitive rate of K. pneumoniae strains to imipenem and meropenem were 93.1% and 89.7%, respectively.Conclusions MRCNS stains were the most frequently detected pathogens in blood cultures in the present study. The characteristic of drug resistance for the pathogens indicated that monitoring of imipenem and meropenem resistant K. pneumoniae should be underlined to prevent nosocomial outbreak. Fungi bloodstream infections of ward such as ICU and department of hemopathology should be enhanced monitored.

Isolation and Drug Resistance Analysis of Swine Salmonella

In this study, 68 fresh pork samples were collected from several major wholesale markets in Dalian City of Liaoning Province to isolate Salmonella using SS agar medium as selective medium. Salmonella isolates were identified with colony morphology observation and PCR method. The resistance of Salmonella iso- lates to 15 antibiotics was analyzed by broth microdilution susceptibility test. Accord- ing to the result, 12 Salmonella strains were isolated from 68 fresh pork samples, indicating a detection rate of 17.64%; 83.33% of Salmonella strains isolated from fresh pork samples could at least resist one antibiotic; Salmonella strains exhibited the strongest resistance to florfenicol （75.0%）, sarafloxacin hydrochloride （66.7%）, neomycin sulfate （66.7%） and doxycycline hydrochloride （66.7%）, followed by oxyte- tracycline （58.3%）, gentamicin sulphate （58.3%） and mequindox （58.3%）; Salmonella strains exhibited relatively low resistance to ciprofloxacin lactate （50.0%）, en- rofloxacin （50.0%）, ciprofloxacin hydrochloride （50.0%）, amoxicillin （16.7%） and col- istin sulphate （16.7%）. Salmonella in fresh pork samples from wholesale markets in Dalian Economic ＆ Technological Development Zone exhibited a high detection rate, and the isolated Salmonella strains showed extremely high resistance to various an- tibiotics. The strong drug-resistance of Salmonella can also be transmitted through the food chain from the food to the people, which should attract sufficient attention.

Study on Drug Resistance and Relative Mechanisms of Chlamydia Trachomatis

Chlamydia Trachomatis (C.T.) is one of the most common pathogens of human sexually transmitted diseases. Treatment of C.T. infection primarily depends on Tetracyclines, Macrolides and Quinolones, but with the wide use of antibiotics an increasing number of drug-resistant Chlamydia trachomatis cases have been reported. This review summarizes the resistant conditions and the possible resistance mechanisms of C.T..