Detection of colistin susceptibility in extended spectrum ? lactamases positive Klebsiella pneumoniae and Escherichia coli clinical isolates by broth disc elution method

Background: Antibiotic resistance is one of the greatest threats in human health. Extended spectrum ? lactamases mediated resistance is prevalent worldwide, Klebsiella pneumoniae and Escherichia coli leap out as this significant ESBL producers conferring resistance to the expanded spectrum cephalosporins. Colistin is being administered as last line therapy for patients that have failed to respond to other available antibiotics that are active against Gram-negative bacteria. Methods: The present study was conducted at school of medical education Kottayam, Kerala from January 2023 to November 2023.During the period of study 150 isolates of K. pneumoniae and 136 isolates of E. coli were collected from various diagnostic microbiology laboratories in Kerala. The colistin susceptibility pattern of ESBL producing isolates was detected by broth disc elution method recommended by CLSI. Results: In this study prevalence of multi-drug resistant is 6% and 9.6% and Extensively-drug resistant is 62% and 63.9% for K. pneumoniae and E. coli respectively. ESBL production was detected as 72% in K. pneumoniae and 79% in E. coli. The colistin susceptibility pattern of ESBL producing K. pneumoniae and E. coli was detected as 76.9% and 87.9% respectively Conclusions: Our result demonstrated that the recent use of colistin as last resort treatment for extensively drug resistant gram-negative bacilli, it is essential to know the prevalence of susceptibility pattern to this antibiotic.

Research progress of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum / 中华临床感染病杂志

It is generally accepted that Mycoplasma hominis and Ureaplasma urealyticum are primarily found in the genitourinary tract and rarely enter the tissues and bloodstream. In recent years，cases of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum have been increasing with a trend of multi-drug resistance，while detection and diagnosis are difficult，leading to treatment delay clinically. This article reviews the latest research progress on the pathogenic characteristics，laboratory diagnosis，infection types，and treatment options of extra-genitourinary system infections caused by Mycoplasma hominis and Ureaplasma urealyticum，in order to provide reference for etiological diagnosis and treatment of the infection.

Drug resistance and homology of diarrheagenic Escherichia coli in sentinel hospital of Fengxian District of Shanghai， 2019‒2022 / 上海预防医学

ObjectiveWe conducted a drug resistance and homology analysis of diarrheagenic Escherichia coli （DEC） in Fengxian District of Shanghai in order to provide a basis for clinical rational drug use， risk monitoring and early warning. MethodsDEC were isolated from diarrheal patients in Fengxian District， Shanghai from 2019 to 2022. The minimum inhibitory concentrations （MIC） of 21 drugs to the DEC were determined. Genotyping and homology analysis were conducted with pulsed-field gel electrophoresis （PFGE）. ResultsThe DEC detection rate of diarrhea cases was 18.99% （131/690）， including enteroaggregative E.coli （EAEC） 64.89% （85/131）， enterotoxigenic E.coli （ETEC） 22.14% （29/131）， enteropathogenic E.coli （EPEC） 12.21% （16/131）， and enterohemorrhagic E.coli （EHEC） 0.76%（1/131）. The DEC detection showed obvious seasonal characteristics with a high incidence in summer. The DEC multidrug resistance rate was 66.41% with a total of 65 drug resistance profiles. The five antimicrobial drugs with the highest resistance rate were ampicillin （60.31%）， nalidixic acid （51.91%）， cefazolin （50.38%）， tetracycline （44.27%）， and cotrimoxazole （35.11%）. The rate of DEC resistance to levofloxacin was significantly increased from 2019 to 2022. Cluster analysis showed that the similarity of 85 EAEC cluster was 58.4%‒100.0%， and 69 band patterns were obtained. The similarity of 29 ETEC cluster was 58.5%‒100.0%， and 13 band patterns were obtained， including 2 dominant band types. The similarity of 16 EAEC clusters was 53.9%‒100.0%， and 15 band patterns were obtained. Five groups of homologous strains were found， consistent with the resistance phenotypes. ConclusionAmong the diarrhea cases， the DEC epidemic intensity is high， the drug resistance situation is severe， and the risk of outbreak infection is high in Fengxian District， Shanghai. Therefore， health monitoring and prevention need to be strengthened.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

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 APCmin/+ 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.

Detection mecA gene and Staphylococcus aureus resistance to several antibiotics isolated from cat ear swabs at a veterinary hospital located at Surabaya ­ Indonesia / Detecção do gene mecA e resistência a diversos antibióticos em Staphylococcus aureus isolados do ouvido de gatos em um hospital localizado em Surabaya ­ Indonesia

Cats are susceptible to S. aureus, which mainly colonizes the nose and ears of these feline species. Otitis externa in cat ears is one of the illnesses produced by S. aureus in animals. Antibiotic therapy for affected animals is the conventional treatment for infections by S. aureus. Antibiotic use during prolonged treatment and given at the wrong doses can cause germs to become resistant. Given this context, research on S. aureus isolated from cat ears and tests for antibiotic resistance and the mecA gene is required. Samples of cat ears were obtained from the Amies media using a sterile cotton swab. Bacterial isolation was done on MSA media, and then the catalase and coagulase assays were used to identify the bacteria. S. aureus isolates were evaluated for sensitivity using disks of the antibiotics cefoxitin, tetracycline, erythromycin, gentamicin, and chloramphenicol connected to MHA media. All positive isolates of S. aureus underwent MRSA testing, and then the mecA gene was detected. The sample investigation revealed that 91% (91/100) were positive for S. aureus, and 3.30% (3/91) were confirmed to be multidrug-resistant (MDR) because they are resistant to 3­4 antibiotic classes. Out of the 12 MRSA isolates analyzed, the mecA gene was detected in one isolate. Inappropriate antibiotic use causes bacterial resistance in pets. Additionally, excessive antibiotic use in a population might develop acquired bacterial resistance to an antibiotic. Antibiotic use in animals must be assessed to administer medication and prevent the development of antibiotic resistance appropriately.(AU)

Gatos são suscetíveis a adquirir S.aureus que colonizam principalmente as narinas e os ouvidos de espécies de felinos. A otite externa no ouvido dos gatos é uma das doenças produzidas pelo S.aureus nos animais. A terapia com antibióticos é o tratamento convencional para as infecções produzidas pelo S.aureus. Os antibióticos utilizados durante o prolongado tratamento e o emprego de sub doses podem selecionar microorganismos resistentes. Com base em tais argumentos torna-se necessária a pesquisa de S.aureus isolados do ouvido dos gatos, bem como, a realização de testes para a resistência a antibióticos e do gene mecA. Empregando swabs estéreis de algodão foram obtidas amostras dos ouvidos dos gatos em meio de Amies. O isolamento bacteriano foi efetuado em meio MAS e os testes catalase e coagulase foram realizados para a identificação das bactérias. A sensibilidade dos isolados de S.aureus foi avaliada com o emprego de discos dos antibióticos cefoxitin, tetraxiclina, eritromicina, gentamicina e cloranfenicol, incorporados no meio MHA. Todos os isolados positivos de S.aureus foram submetidos ao test MRSA para a detecção do gene mecA. A amostra investigada revelou 91% (91/100) de positivos para S.aureus, dos quais, 3,30% (3/91) foram resistentes a múltiplas drogas (MDR) pois foram resistentes a 3-4 classes de antibióticos. De 12 MRSA isolados analisados o gene mecA foi detectado em um isolado. O uso inapropriado de antibióticos é a causa da resistência bacteriana em pets. Adicionalmente o emprego excessivo de antibióticos em uma população pode resultar no desenvolvimento de resistência bacteriana adquirida a antibióticos. O uso de antibióticos em animais deve ser ordenado por uma administração de medicamentos apropriada para prevenir o desenvolvimento da resistência.(AU)

Sirturo- a diarylquinoline (bedaquiline): a novel approach for the treatment of MDR-TB and pre-XDR TB

Sirturo (bedaquiline fumarate) is a new antitubercular class of medicine, lately, FDA, approved and indicated for use as a part of an appropriate applicable combination regimen along with other antitubercular medicines (i. e.; 2nd line anti-TB agents) for pulmonary multidrug-resistant tuberculosis (MDR TB) in grown up with age 12 years to less than 18 years of age and weighing at least 30 kg when an alternative treatment regimen cannot be considered for the reasons of resistance or tolerability. Bedaquiline, an enantiomer chemically belongs to the diarylquinoline (DAR) compound, which is nearly related to fluoroquinolones and chloroquine with differences in their side-chain moiety. Amongst all anti-TB medicines that have been approved, bedaquiline has a unique mechanism, which targets energy metabolism i. e.; adenosine triphosphate of mycobacteria, and eventually leads to bacterial cell lysis. ATP is an essential energy-producing molecule required for metabolic actions and survival of Mycobacteria and also for many other cells. Mycobacteria generally invade into well-encapsulated lung cavities and endosomes of macrophages, which can survive even under low oxygen levels leading to resistance against standard TB drugs. Bedaquiline has a spectrum of activity against drug-susceptible TB and MDR TB. Many clinical trials and studies demonstrated that bedaquiline is a crucial component of a combination regimen for multidrug-resistant TB.

Detection of polymyxin B resistance in Enterobacterales by broth disk elution method

Background: Antibiotic resistance being the critical issue faced by medical field, especially by Gram negative bacteria. It is a great threat in the case of both hospitals acquired and community acquired infections. They possess various mechanisms for their survival. The widespread resistance in Gram negative bacteria has necessitated evaluation of the use of older antimicrobials such as polymyxins. Polymyxins are disfavoured owing to their potential clinical toxicity, especially nephrotoxicity. Thus, they got abandoned in the sixties. But now they are re- emerged and used as last resort antibiotics. Methods: 274 isolates of Enterobacterales including Klebsiella pneumoniae, Escherichia coli, Citrobacter spp. Enterobacter spp. was collected from various diagnostic microbiology laboratories in Kerala. The polymyxin resistance among Enterobacterales by broth disk elution method recommended by CLSI. Results: In this study prevalence of multi drug resistant is 37% and extensively drug resistant strains is 25%. And the threatening fact is that the colistin also shows resistance among Enterobacterales (9.2%). Conclusions: Though the resistance to Polymyxin B is to the lesser side in the present study, increase in resistance to the agent is being documented globally elsewhere. So, rational use of Polymyxin B is warrantied as we could cherish polymyxin B as a 搇ife - saving drug� to avoid no drug available. Knowledge of antimicrobial resistance and development of new antimicrobial agents and improved treatments are essential in the current situation.

ANTIMICROBIAL SUSCEPTIBILITY PATTERN OF UROPATHOGENS AT A TERTIARY CARE HOSPITAL IN CENTRAL INDIA DURING COVID ERA.

Objective: The purpose of this study was to study the bacteriological profile of UTI in patients attending the tertiary care hospital and to study the antimicrobial sensitivity pattern of uropathogens.Methods: This cross-sectional study was conducted after obtaining clearance from the institutional ethics committee. Clean-catch mid-stream urine samples were collected from patients symptomatic of UTIs. Samples were cultured aerobically on CLED agar. Isolates having significant growth (>105CFU/ml) were further processed for identification using standard microbiological techniques and their antimicrobial susceptibility pattern was evaluated by the Standard Kirby Bauer disk diffusion method as per CLSI 2020 guidelines.Results: A total of 480 urine samples were processed, yielding 174 isolates. Escherichia coli (42.50%) was predominant, followed by Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter spp., Proteus spp., Providencia spp., Enterococcus spp., Citrobacter spp. and Morganella morganii. Gram-positive isolates exhibited high sensitivity towards vancomycin, linezolid, meropenem, and piperacillin tazobactum. Enteric coliforms exhibited high sensitivity towards colistin, meropenem, aminoglycosides, and piperacillin tazobactum. Non-fermenters exhibited high sensitivity towards colistin, meropenem, cefepime, and amoxycillin clavulanate.Conclusion: The rampant injudicious irrational overuse of antibiotics has led to the emergence of multi-drug resistant bugs, which is posing a serious challenge to clinicians in the management of infections. Developing therapeutic protocols guided by susceptibility profiles for tuning antibiotic therapy regimens is an important strategy in tackling this menace.

Green synthesis of gold nanoparticles from Sophora flavescens extract and their antibacterial effect against some pathogenic bacteria

Aims@#The current study was aimed to evaluate the antibacterial activity of biogenic synthesized golden nanoparticles from Sophora flavescens Aiton roots aqueous extract against multidrug-resistant (MDR) clinical bacterial isolates.@*Methodology and results@#The green synthesis of gold nanoparticles (AuNPs) was accomplished using S. flavescens roots aqueous extract and examined using many accepted techniques. The antibacterial activity of S. flavescens extract and the aqueous AuNPs at concentrations (7% and 9%) ppm were investigated against two clinical MDR bacteria, including Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa). The findings demonstrate inhibitory activity against the selected MDR bacterial isolates for the aqueous extract of S. flavescens and the aqueous AuNPs noted by the significant decrease in the number of bacteria after treatment with highly significant differences (P≤0.01) compared to the untreated control.@*Conclusion, significance and impact of study@#Sophora flavescens root extracts and their biosynthesized AuNPs with antibacterial activity may find broad applications in fighting MDR pathogenic bacteria and therapeutic manufacturing.

Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.@*METHODS@#The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.@*RESULTS@#A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).@*CONCLUSIONS@#The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.

Advances in genomics of multi-drug resistant Stenotrophomonas / 生物工程学报

Stenotrophomonas species are non-fermentative Gram-negative bacteria that are widely distributed in environment and are highly resistant to numerous antibiotics. Thus, Stenotrophomonas serves as a reservoir of genes encoding antimicrobial resistance (AMR). The detection rate of Stenotrophomonas is rapidly increasing alongside their strengthening intrinsic ability to tolerate a variety of clinical antibiotics. This review illustrated the current genomics advances of antibiotic resistant Stenotrophomonas, highlighting the importance of precise identification and sequence editing. In addition, AMR diversity and transferability have been assessed by the developed bioinformatics tools. However, the working models of AMR in Stenotrophomonas are cryptic and urgently required to be determined. Comparative genomics is envisioned to facilitate the prevention and control of AMR, as well as to gain insights into bacterial adaptability and drug development.

Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.@*METHODS@#Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.@*RESULTS@#Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.@*CONCLUSION@#Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

Characterization of Virulent Bacterial Isolates Associated with Multi-Drug Resistance among Patients with Surgical Site Infections in Selected Specialist Hospitals in Calabar, Nigeria

Aims: Increasing research findings have documented the continuous emergence and threats posed by drug resistant clinical isolates from post-operative wound infections to commonly used antibiotics globally. This hospital-based study investigated virulent bacterial pathogens implicated with post-operative wound infections among surgical site infection (SSI) patients in Calabar, Nigeria and determined their antibiotic resistance pattern. Methodology: A total of 127 bacterial isolates of different genus from 110 SSI patients, were isolated from pus and surgical wound exudates and fully characterized using standard bacteriological procedures. Antimicrobial susceptibility patterns of isolates were determined using Kirby- Bauer disk diffusion method, following the guidelines by Clinical Laboratory Standard Institute (CLSI). Results: Multi-drug resistant bacteria isolated and their percentage frequency were coagulase Negative Staphylococci (21.3%), Staphylococcus aureus (19.7%), Pseudomonas aeruginosa (14.2%), Escherichia coli (11.8%), Klebsiella pneumoniae (9.4%), Enterococcus faecium (6.3), Enterobacter cloacae (4.7%), Proteus mirabilis (4.7%), Acinetobacter baumannii (3.1%), Pseudomonas putida (3.1%) and Aerococcus viridans (1.6%). Among gram-positive bacteria isolated, S. aureus showed highest resistance to several antimicrobials (100% to oxacillin, 96% to ciprofloxacin, 92% to levofloxacin, and 76% resistance to vancomycin). All recovered S. aureus isolates were cefoxitin screen positive indicating possible MRSA isolates. Additionally, among Gram-negative isolates K. pneumoniae was found to possess higher resistance to several antibiotics (66.7% resistance to each of ciprofloxacin, levofloxacin, ceftazidime, trimethoprim /sulfamethoxazole, cefazolin, ampicillin, tobramycin and 58.3% resistance to each of ceftriaxone, gentamicin, and ampicillin/sulbactam). Statistical analysis of categorical variables of study subjects revealed that length of hospital stay, type of surgery, previous admission history, antibiotic use, and age were significant (p<0.05) in SSI outcome of patients, while patients� gender was not significant (p>0.05) in SSI outcome. Conclusion: Adherence to measures of strict infection control, optimal preoperative, intraoperative, and postoperative patient care, including multifaceted approaches involving surveillance, and antimicrobial stewardship, are vital to SSI treatment outcomes.

A study of clinical and treatment profile of tuberculosis patients attending DOTS centre at Primary Health Centre

Introduction: Tuberculosis (TB) is an age-old disease killing significant number of humans over history and one of the major cause of morbidity and mortality, especially in developing and underdeveloped countries. It killed 1.4 million people annually worldwide in the year 2019. India had 2.69 million cases in 2019, according to TB report 2020. Despite the presence of the programme for it's control, TB continues to threaten the population due to emergence of more and more resistance cases challenging it's elimination. This study reflects the annual burden of tuberculosis in an area served by a Primary Health Centre in Urban Delhi and the treatment outcomes. The records of the patients attendingMethods: the DOTS centre was obtained from the treatment register at Primary Health Centre, Palam, Delhi. The records of patients visiting between April 2020 to March 2021 were included. Data analysis was done on Statistical Package for the Social Sciences (SPSS) version 22 and appropriate statistical tests were applied. The total number ofResults & Conclusion: tuberculosis patients registered from April 2020 to March 2021 were 260. Out of these 260 patients, 155 (59.6%) were pulmonary and 105 (40.4%) were extra-pulmonary. A total of 175 (67.3%) were microscopically confirmed and 85 (32.7%) were clinically/radiologically diagnosed.

Anti pathogenic studies of new mixed ligand metal chelates

Drug discovery aimed at the methodical extermination of life-threatening bacterial infection, especially considering the emergence of multi-drug resistance of pathogenic bacteria has remained a challenge for medicinal inorganic chemistry. In this article, the mixed ligand complexes of Cu (II), Co (II), and Ni (II) containing heterocyclic ligands were synthesized and characterized by IR, LC-MS, UV, and TG-DTA. Complexes are screened for Anti-microbial activity against human pathogenic bacteria.

Evaluation and management of application of antibiotics in PICU / 中国小儿急救医学

Antibiotics are the most commonly used medicines in PICU.For children with severe infection, it is very important to ensure the curative effect of patients and reduce the adverse effects of antibiotic abuse through reasonable empirical initial use of antibiotics, timely evaluation and regulation, and appropriate course of antibiotic treatment.This review discussed several main problems of clinical application of antibiotics in PICU, in order to help clinicians in PICU improve the evaluation and management of antibiotics use.

Research progress on drug resistance mechanism and treatment of Stenotrophomonas maltophilia / 中华临床感染病杂志

Stenotrophomonas maltophilia is a gram-negative bacillus which widely exists in natural and hospital environment, and it is also one of the common opportunistic pathogens in clinical settings. The virulence and pathogenicity of Stenotrophomonas maltophilia are weak, however, due to resistance to a variety of antibacterial drugs, it can cause bloodstream infections or pneumonia in immunocompromised or critically ill patients, leading to poor prognosis. Moreover, the inherent drug resistance and increasing acquired drug resistance may make the treatment of the first line antibiotics, like trimethoprim-sulfamethoxazole or quinolone ineffective. Therefore, it is important to understand the drug resistance mechanism and the main countermeasures for it. In this article, the research progress on drug resistance mechanism and treatment for Stenotrophomonas maltophilia are reviewed.

Effects of tigacycline-based combination therapy onprocalcitonin, high sensitivity C-reactive protein and interleukin-6 in patients with multiple drug-resistant acinetobacterbaumannii post-operative abdominal infection in intensive care unit / 中国医师进修杂志

Objective:To explore the effects of tigacycline-based combination therapy on procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) in patients with multiple drug-resistant acinetobacterbaumannii post-operative abdominal infection in intensive care unit (ICU).Methods:Seventy-five patients with multiple drug-resistant acinetobacter baumannii post-operative abdominal infection in ICU admitted to West Central Hospital of Hainan Prorvincefrom October 2015 to October 2018 were selected and divided into the control group (37cases) and the observation group (38 cases) according to random number table method. The control group was treated with cefoperazone-sulbactam on the basis of routine treatment, while the observation group was treated with tegacycline on the basis of the control group. Both groups were treated for 1 week. The clearance of acinetobacterbaumannii and clinical efficacy of the two groups were counted; the levels of serum PCT, hs-CRP and IL-6 and ummune function were compared.Results:The clearance rate of acinetobacterbaumannii in the observation group was significantly higher than that in the control group: 76.32%(29/38) vs. 54.05%(20/37), χ2 = 4.10, P = 0.043. Compared with before treatment, the levels of serum PCT, hs-CRP and IL-6 in the two groups were decreased after 1 week of treatment, and the levels of serum PCT, hs-CRP and IL-6 in the observation group were lower than those in the control group ( P<0.05). Compared with before treatment, the levels of peripheral blood CD 3+, CD 4+, CD 4+/CD 8+ were increased and peripheral blood CD 8+ was decreased in both groups, and the levels of peripheral blood CD 3+, CD 4+, CD 4+/CD 8+ in the observation group were higher than those in the control group ( P<0.05), while the level of peripheral blood CD 8+ in the observation group was lower than that in the control group ( P<0.05). The total effective rate in the observation group was significantly higher than that in the control group: 89.47% (34/38) vs. 67.57% (25/37), χ2 = 4.13, P<0.05. Conclusions:Tigacycline combined with cefoperazone-sulbactam in the treatment of intra-abdominal infection after surgery of acinetobacterbaumannii in ICU could reduce the levels of serum PCT, hs-CRP, IL-6, reduce the body′s inflammatory response and improve the immune function, and improve the treatment efficiency of intra-abdominal infection.

Prevention and control of antimicrobial resistance using CRISPR-Cas system: a review / 生物工程学报

Bacterial multi-drug resistance (MDR) is a global challenge in the fields of medicine and health, agriculture and fishery, ecology and environment. The cross-region spread of antibiotic resistance genes (ARGs) among different species is one of the main cause of bacterial MDR. However, there is no effective strategies for addressing the intensifying bacterial MDR. The CRISPR-Cas system, consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated proteins, can targetedly degrade exogenous nucleic acids, thus exhibiting high application potential in preventing and controlling bacterial MDR caused by ARGs. This review briefly introduced the working mechanism of CRISPR-Cas systems, followed by discussing recent advances in reducing ARGs by CRISPR-Cas systems delivered through mediators (e.g. plasmids, bacteriophages and nanoparticle). Moreover, the trends of this research field were envisioned, providing a new perspective on preventing and controlling MDR.

Z-guggulsterone reversed multi-drug resistance of hepatocarcinoma chemotherapy through down-regulating a PXR/P-gp pathway / 中国药理学通报

Aim To investigate the improved effects of Z-guggulsterone on the chemotherapy agents-induced proliferation and apoptosis through regulating PXR(pregnane X receptor)/P-gp(P-glycoprotein)signaling pathway in human hepatocellular carcinoma cells.Methods HepG2 cells were treated with Z-guggulsterone, DDP(cis-platinum)and 5-FU(5-fluorouracil)alone or in combination.CCK-8(Cell Counting Kit-8), Annexin-FITC/PI(Annexin V-fluorescein isothiocyanate isomer/propidium iodide)flow cytometry, RT-qPCR(Real-time quantitively Polymerase Chain Reaction)and Western blot were used to determine cell proliferation, apoptosis, the expression of MDR1 mRNA, PXR and P-gp respectively.Results Compared to DDP or 5-FU treatment alone, Z-guggulsterone(30 μmol·L-1)enhanced the inhibitory effects of DDP or 5-FU on the proliferation and apoptosis of HepG2 cells.Z-guggulsterone(30 μmol·L-1)also significantly reduced the expression levels of PXR,P-gp and MDR1 mRNA in HepG2 cells.Further research demonstrated that rifampicin, one agonist of PXR, increased the expression of PXR and P-gp, while Z-guggulsterone reversed its effects.Meanwhile, the expressions of PXR and P-gp were reduced by ketoconazole, one antagonist of PXR, and further decreased by co-administration with Z-guggulsterone.Conclusion Z-guggulsterone can improve the effects of chemotherapy on the proliferation and apoptosis of hepatocellular carcinoma cell lines by down-regulating the PXR/P-gp signaling pathway.