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)

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.

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.

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.