scholarly journals The association between MDR1 C3435T genetic polymorphism and the risk of multidrug-resistant epilepsy in Egyptian children

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dina Salama Abd Elmagid ◽  
Maha Abdelsalam ◽  
Hend Magdy ◽  
Noha Tharwat
Keyword(s):  
Genetic Polymorphism ◽  
Sodium Valproate ◽  
Statistical Significance ◽  
Resistance Mechanism ◽  
Therapy Resistance ◽  
Multidrug Resistant ◽  
Good Prognosis ◽  
Genotype Distribution ◽  
Egyptian Children ◽  
Drug Resistant Epilepsy

Abstract Background Epilepsy is a chronic disease affecting about 2% of the population and is considered a serious neurological disease. Despite its good prognosis, 20–30% of epileptic patients were not cured of their seizures even with the many trials of antiepileptic drug (AED) therapy. The resistance mechanism is still unclear, maybe due to the effect of the genetic factors on the bioavailability of the drugs. Consequently, the association between therapy resistance and the presence of a gene called “multidrug resistance 1 (MDR1)” had been proposed. Thus, the present study aimed to understand the relationship between the genetic polymorphism of MDR1C3435T and the resistance to AEDs. Result A non-significant association was found between MDR1 C3435T single-nucleotide polymorphism (SNP) and drug-resistant epilepsy. However, there was statistical significance in the association between the drug type and the genotype distribution, in cases that were maintained on sodium valproate and MDR1C3435T genotype. Conclusion Possible involvement of the MDR1 gene C 3435T polymorphism with sodium valproate resistance clarifies the importance of genetic variability in response to the drug and may help to find novel genetic therapy for epilepsy, by targeting the biological mechanisms responsible for epilepsy in each specific individual. Future studies with bigger sample sizes and in other racial populations will be necessary.

scholarly journals ROS-1 NSCLC therapy resistance mechanism

2021 ◽  
Vol 4 ◽  
pp. 16-16
Author(s):  
Miguel García-Pardo ◽  
Antonio Calles
Keyword(s):  
Resistance Mechanism ◽  
Therapy Resistance

scholarly journals Plasmid Derived AmpC Genotypes among the Multidrug Resistant Enterobacteriaceae Strains Isolated from Urine Samples in Southern India

2021 ◽  
Author(s):  
P Ronni Mol ◽  
Ganesan Shanthi ◽  
Khalid Bindayna
Keyword(s):  
Clinical Laboratory ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Urine Samples ◽  
Pcr Analysis ◽  
Genotype Distribution ◽  
Cross Sectional ◽  
Beta Lactamases ◽  
Hospital Infection Control ◽  
Tract Infections

Introduction: The most common pathogens causing Urinary Tract Infections (UTI) in community and hospital settings are Enterobacteriaceae. Antibiotic resistance is a major problem worldwide because of an increase in the use of antibiotics. Production of Extended Spectrum Beta-Lactamases (ESBLs) and AmpC beta-lactamases is the most common cause of resistance among Enterobacteriaceae (AmpC). Initially, AmpC β-lactamases received less attention globally, but now it has become a rising problem. Detection of AmpC β-lactamases expressing microbes is a requirement for addressing surveillance, for problems of hospital infection control, and for choosing optimal antimicrobial therapy. Aim: To study the genotype distribution of plasmid mediated AmpC β-lactamase produced in Enterobacteriaceaestrains isolated from urine samples. Materials and Methods: A cross-sectional study based on clinical laboratory surveillance was conducted from July 2019 to February 2020. Sixty Enterobacteriaceae isolates were identified by standard biochemical reactions. AmpC screening were done by cefoxitin disk diffusion and confirmed by an inhibitor-based assay using boronic acid. The presence of six plasmid mediated AmpC genes was determined by multiplex Polymerase Chain Reaction (PCR). Statistical Package for the Social Science (SPSS) version 20.0 was used to obtain descriptive data. Results: Among 60 Enterobacteriaceae isolates, 23 (38.3%) were cefoxitin-resistant isolates which contain Escherichia colistrain (n=17) while the remaining samples consist ofKlebsiella pneumoniae (n=5) and Proteus mirabilis strains (n=1). AmpC β-lactamase production was phenotypically confirmed in 12(20%) isolates and genotypically confirmed by PCR analysis in 16(26.6%) of all the urine isolates. In the present study, 3(13%), 2 (8.6%) of cefoxitin resistant isolates harboured the DHA, EBC gene and 1(4.3%) each harboured FOX and CIT gene, and 9(39.1%) harboured a combination of the genes. Conclusion: The present study suggested the predominant existence of plasmid mediated AmpC producers in Multi-Drug Resistant (MDR) Escherichia coli and Klebsiella pneumoniae. We suggest continuous surveillance is important to effectively control the spread of these strains and for optimal clinical outcome.

Efflux pump gene expression study using RNA-seq in multidrug-resistant TB

2021 ◽  
Vol 25 (12) ◽  
pp. 974-981
Author(s):  
J. J. Lee ◽  
H. Y. Kang ◽  
W-I. Lee ◽  
S. Y. Cho ◽  
Y. J. Kim ◽  
...  
Keyword(s):  
Wild Type Strain ◽  
Efflux Pump ◽  
Expression Patterns ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Regulatory Genes ◽  
Control Group ◽  
Rna Expression ◽  
Rna Seq ◽  
Expression Study

BACKGROUND: The mechanism underlying kanamycin (KM) resistance in Mycobacterium tuberculosis is not well understood, although efflux pump proteins are thought to play a role. This study used RNA-seq data to investigate changes in the expression levels of efflux pump genes following exposure to KM.METHODS: RNA expression of efflux pump and regulatory genes following exposure to different concentrations of KM (minimum inhibitory concentration MIC 25 and MIC50) in rrs wild-type strain and rrs A1401G mutated strain were compared with the control group.RESULTS: The selected strains had differential RNA expression patterns. Among the 71 putative efflux pump and regulatory genes, 46 had significant fold changes, and 12 genes (Rv0842, Rv1146, Rv1258c, Rv1473, Rv1686c, Rv1687c, Rv1877, Rv2038c, Rv3065, Rv3197a, Rv3728 and Rv3789) that were overexpressed following exposure to KM were thought to contribute to drug resistance. Rv3197A (whiB7) showed a distinct fold change based on the concentration of KM.CONCLUSION: The significant changes in the expression of the efflux pump and regulatory genes following exposure to KM may provide insights into the identification of a new resistance mechanism.

scholarly journals Persistent Bacteremia fromPseudomonas aeruginosawithIn VitroResistance to the Novel Antibiotics Ceftolozane-Tazobactam and Ceftazidime-Avibactam

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Louie Mar Gangcuangco ◽  
Patricia Clark ◽  
Cynthia Stewart ◽  
Goran Miljkovic ◽  
Zane K. Saul
Keyword(s):  
Susceptibility Testing ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Blood Cultures ◽  
The Novel ◽  
First Case ◽  
Persistent Bacteremia ◽  
Novel Antibiotics

Ceftazidime-avibactam and ceftolozane-tazobactam are new antimicrobials with activity against multidrug-resistantPseudomonas aeruginosa. We present the first case of persistentP.aeruginosabacteremia within vitroresistance to these novel antimicrobials. A 68-year-old man with newly diagnosed follicular lymphoma was admitted to the medical intensive care unit for sepsis and right lower extremity cellulitis. The patient was placed empirically on vancomycin and piperacillin-tazobactam. Blood cultures from Day 1 of hospitalization grewP.aeruginosasusceptible to piperacillin-tazobactam and cefepime identified using VITEK 2 (Biomerieux, Lenexa, KS). Repeat blood cultures from Day 5 grewP.aeruginosaresistant to all cephalosporins, as well as to meropenem by Day 10. Susceptibility testing performed by measuring minimum inhibitory concentration byE-test (Biomerieux, Lenexa, KS) revealed that blood cultures from Day 10 were resistant to ceftazidime-avibactam and ceftolozane-tazobactam. The Verigene Blood Culture-Gram-Negative (BC-GN) microarray-based assay (Nanosphere, Inc., Northbrook, IL) was used to investigate underlying resistance mechanism in theP.aeruginosaisolate but CTX-M, KPC, NDM, VIM, IMP, and OXA gene were not detected. This case report highlights the well-documented phenomenon of antimicrobial resistance development inP.aeruginosaeven during the course of appropriate antibiotic therapy. In the era of increasing multidrug-resistant organisms, routine susceptibility testing ofP. aeruginosato ceftazidime-avibactam and ceftolozane-tazobactam is warranted. Emerging resistance mechanisms to these novel antibiotics need to be further investigated.

Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors

2019 ◽  
Vol 27 (22) ◽  
pp. 27279-27292 ◽  
Author(s):  
Priti Prabhakar Yewale ◽  
Kiran Bharat Lokhande ◽  
Aishwarya Sridhar ◽  
Monika Vaishnav ◽  
Faisal Ahmad Khan ◽  
...  
Keyword(s):  
River Water ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Molecular Profiling ◽  
Potential Inhibitors

scholarly journals Gene Expression Indicates Altered Immune Modulation and Signaling Pathway Activation in Ovarian Cancer Patients Resistant to Topotecan

2019 ◽  
Vol 20 (11) ◽  
pp. 2750 ◽  
Author(s):  
Otília Menyhárt ◽  
János Tibor Fekete ◽  
Balázs Győrffy
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Disease Progression ◽  
Immune Modulation ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Therapy Resistance ◽  
Treatment Regimens ◽  
Pathway Activation ◽  
Short Period

Epithelial ovarian cancer (EOC) is one of the deadliest gynecological malignancies. Topotecan remains an essential tool in second-line therapy; even so, most patients develop resistance within a short period of time. We aimed to identify biomarkers of topotecan resistance by using gene expression signatures derived from patient specimens at surgery and available subsequent responses to therapy. Gene expression was collected for 1436 patients and 10,103 genes. Based on disease progression, patients were categorized as responders/nonresponders depending on their progression free survival (PFS) state at 9, 12, 15 and 18 months after surgery. For each gene, the median expression was compared between responders and nonresponders for two treatment regimens (chemotherapy including/excluding topotecan) with Mann–Whitney U test at each of the four different PFS cutoffs. Statistical significance was accepted in the case of p < 0.05 with a fold change (FC) ≥ 1.44. Four genes (EPB41L2, HLA-DQB1, LTF and SFRP1) were consistently overexpressed across multiple PFS cutoff times in initial tumor samples of patients with disease progression following topotecan treatment. A common theme linked to topotecan resistance was altered immune modulation. Genes associated with disease progression after systemic chemotherapy emphasize the role of the initial organization of the tumor microenvironment in therapy resistance. Our results uncover biomarkers with potential utility for patient stratification.

scholarly journals Automated outbreak detection of hospital-associated pathogens: Value to infection prevention programs

2020 ◽  
Vol 41 (9) ◽  
pp. 1016-1021
Author(s):  
Meghan A. Baker ◽  
Deborah S. Yokoe ◽  
John Stelling ◽  
Ken Kleinman ◽  
Rebecca E. Kaganov ◽  
...  
Keyword(s):  
Infection Prevention ◽  
Detection System ◽  
Statistical Significance ◽  
Prevention Programs ◽  
Multidrug Resistant ◽  
Outbreak Detection ◽  
Convenience Sample ◽  
Clostridioides Difficile ◽  
Surveillance Programs ◽  
Infection Preventionists

AbstractObjective:To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms.Design:Multicenter retrospective cohort study.Setting:The study included 43 hospitals using a common infection prevention surveillance system.Methods:A space–time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods.Results:We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals’ surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work.Conclusions:Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.

scholarly journals Lack of association between C3435T nucleotide MDR1 genetic polymorphism and multidrug-resistant epilepsy

Seizure ◽  
2006 ◽  
Vol 15 (5) ◽  
pp. 344-347 ◽  
Author(s):  
Dong Wook Kim ◽  
Manho Kim ◽  
Sang Kun Lee ◽  
Rami Kang ◽  
Seo-Young Lee
Keyword(s):  
Genetic Polymorphism ◽  
Multidrug Resistant

Can we identify a group of breast cancer patients with a good prognosis despite four or more positive (4+) axillary nodes using a tissue microarray (TMA)?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10582-10582
Author(s):  
S. J. Crabb ◽  
C. D. Bajdik ◽  
C. H. Speers ◽  
D. G. Huntsman ◽  
K. A. Gelmon
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factors ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Good Prognosis ◽  
Axillary Lymph ◽  
Long Term Outcome ◽  
Cox Regression Analysis ◽  
Axillary Nodes

10582 Background: Although breast cancer with 4+ axillary lymph nodes generally carries a poor prognosis, we hypothesized that a good prognostic subgroup of such patients would be identifiable by immunohistochemical (IHC) biomarkers. Methods: Patients with primary breast cancer with 4+ axillary nodes and no metastatic disease at diagnosis were identified from a large clinically annotated TMA of formalin-fixed paraffin-embedded archival breast cancers and analyzed for eight IHC based biomarkers: estrogen receptor, HER2, carbonic anhydrase IX, EGFR, CK 5/6, progesterone receptor, p53 and Ki67. Expression of each biomarker was scored 0 or 1 to indicate good or bad prognosis based on univariate analysis of relapse free survival (RFS). Patients were banded as having a total score of 0 (i.e. each biomarker predicted a good outcome), 1–4 or 5–8. Kaplan Meier and Cox regression analysis of RFS outcomes was performed. 10 year RFS for each band was compared to the mean of predicted outcomes based on the prognostic tool Adjuvant! ( www.adjuvantonline.com ). Results: 313 eligible patients were identified and complete data were available for 228. The subset of 228 was similar to the larger group of 313 with respect to RFS and conventional prognostic factors. 10 year RFS for the 228 patients was 39.5% (standard error, SE 3.4%). The subgroup of 37 (16%) scoring zero for all 8 biomarkers had a mean 10 year RFS of 77.6% (SE 7.0). Mean 10 year RFS for the bands scoring 1–4 (154 patients, 68%) and 5–8 (37 patients, 16%) were 34.9% (SE 4.1) and 19.0% (SE 6.9) respectively. Mean 10 year RFS predictions by Adjuvant! were 35.9% (SE 2.6), 34.5% (SE 1.2) and 34.3% (SE 2.3) respectively. In multivariate analysis with conventional prognostic factors, the banded biomarker score retained statistical significance for predicting RFS (p=0.0007) along with estrogen receptor status (p=0.03) and tumour size (p=0.01). Conclusions: This TMA biomarker panel identified a breast cancer subgroup with good prognosis despite extensive axillary node involvement. Long term outcome was markedly better than that predicted by conventional prognostic factors. If validated, treatment decisions and clinical trial stratification might be modified using this new score. No significant financial relationships to disclose.

scholarly journals Prominence of an O75 Clonal Group (Clonal Complex 14) among Non-ST131 Fluoroquinolone-Resistant Escherichia coli Causing Extraintestinal Infections in Humans and Dogs in Australia

2012 ◽  
Vol 56 (7) ◽  
pp. 3898-3904 ◽  
Author(s):  
Joanne L. Platell ◽  
Darren J. Trott ◽  
James R. Johnson ◽  
Peter Heisig ◽  
Anke Heisig ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clonal Complex ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Phylogenetic Group ◽  
Mechanism Analysis ◽  
Content Type ◽  
Clonal Group ◽  
E Coli ◽  
Animal Medicine

ABSTRACTFluoroquinolone (FQ)-resistant extraintestinal pathogenicEscherichia coli(FQrExPEC) strains from phylogenetic group B2 are undergoing epidemic spread. Isolates belonging to phylogenetic group B2 are generally more virulent than otherE. coliisolates; therefore, resistance to FQs among group B2 isolates is concerning. Although clonal expansion of sequence type 131 (ST131) is a major factor, the contribution of additional clonal groups has not been quantified. Group B2 FQrExPEC isolates from humans (n= 250) and dogs (n= 12) in Australia were screened for ST131, a recently recognized and rapidly emerging multidrug-resistant and virulent clonal group that is important in both human and companion animal medicine. Non-ST131 isolates underwent virulence genotyping, PCR-based O typing, partial multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and FQ resistance mechanism analysis. Of 49 non-ST131 isolates (45 human, 4 canine), 49% (24 human, 2 canine) represented O-type O75 and exhibited conserved virulence genotypes (F10papAallele,iha,fimH,sat,vat,fyuA,iutA,kpsMII,usp,ompT,malX, K1/K5 capsule) and MLST allele profiles corresponding with clonal complex CC14. Two clusters, each containing canine and human isolates, were identified by PFGE (differentiated by K1 and K5 capsules). Australian FQrO75 isolates exhibited commonality with an historical FQ-susceptible O75 urosepsis isolate (also CC14). The isolation from humans and dogs of highly similar FQrderivatives of the classic O75:K1/K5 (CC14) ExPEC lineage suggests recent acquisition of FQ resistance and potential cross-host-species transfer. This lineage should be targeted with ST131 in future epidemiological investigations of FQrExPEC.

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