Abstract 4029: The impact of multiple drug resistance mechanisms on microarray predictive gene signature performance.

An obstacle to drug development, particularly in this era of multiple drug resistance, is the under-appreciation for the role the host environment plays in microbial response to drugs. With the rise in fungal infection and drug resistance, particularly in individuals with co-morbidities, the influence serum and its components have on antimicrobial susceptibility requires assessment. This study examined the impact of physiologically relevant glucose and insulin levels in the presence and absence of 50 % human plasma on MICs for clinical isolates of Candida lusitaniae, Candida parapsilosis, Candida albicans, Candida tropicalis, Candida glabrata, Candida krusei and Cryptococcus neoformans. The addition of insulin or glucose at physiologic levels in RPMI medium alone altered the MIC in either a positive or negative fashion, depending on the organisms and drug tested, with C. glabrata most significantly altered with a 40, >32- and 46-fold increase in MIC for amphotericin B, itraconazole and miconazole, respectively. The addition of candida-antibody negative plasma also affected MIC, with the addition of glucose and insulin having a tandem effect on MIC. These findings indicate that phenotypic resistance of Candida and Cryptococcus can vary depending on the presence of insulin with glucose and plasma. This modulation of resistance may help explain treatment failures in the diabetic population and facilitate the development of stable drug-resistant strains. Furthermore, these findings indicate the need for a precision approach in the choice of drug treatment and drug development.

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Flavonoids overcome drug resistance to cancer chemotherapy by epigenetically modulating multiple mechanisms

Current Cancer Drug Targets ◽

10.2174/1568009621666210203111220 ◽

2021 ◽

Vol 21 ◽

Author(s):

Kenneth K.W. To ◽

William C.S. Cho

Keyword(s):

Drug Resistance ◽

Cancer Cells ◽

Cancer Chemotherapy ◽

Animal Studies ◽

Multiple Drug Resistance ◽

Resistance Mechanisms ◽

Multiple Drug ◽

Full Potential ◽

Cancer Proliferation ◽

Genes Encoding

Drug resistance is the major reason accounting for the treatment failure in cancer chemotherapy. Dysregulation of the epigenetic machineries is known to induce chemoresistance. It was reported that numerous genes encoding the key mediators in cancer proliferation, apoptosis, DNA repair, and drug efflux are dysregulated in resistant cancer cells by aberrant DNA methylation. The imbalance of various enzymes catalyzing histone post-translational modifications is also known to alter chromatin configuration and regulate multiple drug resistance genes. Alteration in miRNA signature in cancer cells also gives rise to chemoresistance. Flavonoids are a large group of naturally occurring polyphenolic compounds ubiquitously found in plants, fruits, vegetables and traditional herbs. There has been an increasing research interest in the health-promoting effects of flavonoids. Flavonoids were shown to directly kill or re-sensitize resistant cancer cells to conventional anticancer drugs by epigenetic mechanisms. In this review, we summarize the current findings about the circumvention of drug resistance by flavonoids through correcting the aberrant epigenetic regulation of multiple resistance mechanisms. More investigations including the evaluation of synergistic anticancer activity, dosing sequence effect, toxicity in normal cells, and animal studies, are warranted to establish the full potential of the combination of flavonoids with conventional chemotherapeutic drugs in the treatment of cancer with drug resistance.

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OP115 Effect Of Multiple Drug Resistance On Costs For Patients With Intra-Abdominal Infections in China

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462317001799 ◽

2017 ◽

Vol 33 (S1) ◽

pp. 52-52

Author(s):

Xuemei Zhen ◽

Yuanyuan Li ◽

Yixi Chen ◽

Peng Dong ◽

Stephanie Liu ◽

...

Keyword(s):

Drug Resistance ◽

Antimicrobial Agents ◽

Multiple Drug Resistance ◽

National Level ◽

Multiple Drug ◽

Real World Data ◽

Societal Costs ◽

Multiple Variables ◽

Abdominal Infections ◽

The Impact

INTRODUCTION:Multiple drug resistance (MDR) intra-abdominal infections (IAIs) are associated with noteworthy direct and societal costs. Compared to previous studies, the present one takes both resistance rate and total medical costs (TMCs) into consideration, focusing on the impact of MDR on TMCs in IAIs, as well as further estimating the additional costs at a national level.METHODS:All inpatients discharged between 1 January 2014, and 31 December 2015 from a teaching hospital were included. Due to limits in budget and the large number of inpatients, the randombetween (bottom, top) function was applied to randomly select 40 percent of patients per year. Subsequently, we manually screened out 254 patients with IAIs, according to the International Classification of Disease (tenth revision) and electronic medical records. Eventually, 101 IAIs patients were included, in which 37 were infected by non-MDR bacteria and 64 by MDR bacteria. The Kruskal-wallis non-parametric test and multiple linear regression were employed to analyze the effect of single and multiple variables on TMCs.RESULTS:Compared to patients with non-MDR infections, those with MDR were associated with significantly higher TMCs, higher antimicrobial costs, increased insurance, combination antimicrobial therapy, higher usage of antimicrobial agents, greater number of pathogens, longer length of stay, and longer intensive care unit stays. In addition, the average TMCs among patients with MDR were CNY131,801.17 (1USD was equal to CNY 6.227 in 2015), which were CNY 90,200.99 higher than those with non-MDR infections. If our results are generalizable to the whole country, the total attributable TMCs are estimated to be CNY37.06 billion, and the societal costs of CNY111.18 billion in 2015.CONCLUSIONS:This real-world data analysis demonstrated the significant excessive burden MDR infections are posing to the current Chinese healthcare system in terms of both TMCs and healthcare resource utilization. Enhanced antimicrobial stewardship in China is necessary to curb the distribution of MDR bacteria.

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Overcoming multiple drug resistance mechanisms in medulloblastoma

Acta Neuropathologica Communications ◽

10.1186/2051-5960-2-57 ◽

2014 ◽

Vol 2 (1) ◽

Cited By ~ 29

Author(s):

Ramadhan T Othman ◽

Ioanna Kimishi ◽

Tracey D Bradshaw ◽

Lisa CD Storer ◽

Andrey Korshunov ◽

...

Keyword(s):

Drug Resistance ◽

Multiple Drug Resistance ◽

Resistance Mechanisms ◽

Multiple Drug

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Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7/Dox breast cancer cells

Biochimie ◽

10.1016/j.biochi.2016.01.014 ◽

2016 ◽

Vol 124 ◽

pp. 53-64 ◽

Cited By ~ 22

Author(s):

Geetika Chakravarty ◽

Aditi Mathur ◽

Pallavi Mallade ◽

Samantha Gerlach ◽

Joniece Willis ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Multiple Drug Resistance ◽

Resistance Mechanisms ◽

Multiple Drug ◽

Mcf 7

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Targeting Drug Chemo-Resistance in Cancer Using Natural Products

Biomedicines ◽

10.3390/biomedicines9101353 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1353

Author(s):

Wamidh H. Talib ◽

Ahmad Riyad Alsayed ◽

Muna Barakat ◽

May Ibrahim Abu-Taha ◽

Asma Ismail Mahmod

Keyword(s):

Drug Resistance ◽

Natural Products ◽

Multiple Drug Resistance ◽

Basic Research ◽

Resistance Mechanisms ◽

Mechanisms Of Action ◽

Chemotherapeutic Agents ◽

Multiple Drug ◽

Therapeutic Effects ◽

Cancer Resistance

Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

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Genetyping of Carbapenem-resistant Organisms Isolated from Clinical Isolates Received from Tertiary Care Hospitals of Ahmedabad, Gujarat

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.3.65 ◽

2021 ◽

Vol 15 (3) ◽

pp. 1689-1696

Author(s):

Anurag D. Zaveri ◽

Dilip N. Zaveri ◽

Lakshmi Bhaskaran

Keyword(s):

Drug Resistance ◽

Molecular Characterization ◽

Multiple Drug Resistance ◽

Tertiary Care ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Clinical Isolates ◽

Multiple Drug ◽

Tertiary Care Hospitals

The world is seeing a continuous rise in the levels of antibiotic resistance1. Organisms develop new resistance mechanisms, emerge, and spread the resistance worldwide, making it challenging to treat common infectious diseases. In the current study, clinical isolates received between the years 2017 to 2020 were cultured and the isolated organisms were screened for antibiotic resistance; isolates with multiple drug resistance were further subjected to confirmatory screening through Combined Disc Test (CDT) and Modified Hodge Test (M.H.T.), and molecular characterization to be finally tested for gene expression analysis. Molecular characterization involved screening of genes blaVIM-2, blaKPC-3, blaNDM-1, and blaIMP-11 responsible for imparting carbapenem drug resistance2. From the laboratories of tertiary care hospitals, a total of 1452 clinical isolates were collected and identified. The organisms were subjected to antibiotic susceptibility screening and carbapenem resistance screening. The isolates found positive in the screenings were subjected to molecular characterization for genes, blaVIM-2, blaKPC-3, blaNDM-1, and blaIMP-11, responsible for imparting carbapenem drug resistance. Most of the isolates were resistant variably to aminoglycosides but were found to be resistant to fluoroquinolones and β-lactams group of antibiotics. Carbapenem activity was detected in twelve percent of total isolates and 27 percent among multidrug-resistant isolates. blaNDM-1 gene was found present in 77% isolates, and five organisms among the total number of organisms showed pan drug resistance.

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