scholarly journals Multi-Drug Resistant Gram-Negative Bacteria: Antibiotic-Resistance and New Treatment Strategies

2017 ◽  
Vol 02 (02) ◽  
Author(s):  
Maria Teresa Mascellino ◽  
Massimiliano De Angelis ◽  
Alessandra Oliva
Keyword(s):  
Antibiotic Resistance ◽  
Treatment Strategies ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
New Treatment

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR) or extensive drug resistant (XDR) bacterial strains. Most recently, a novel acquired plasmid mediated resistance mechanism to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR and XDR gram-negative bacteria, has been reported. Plasmid mediated colistin resistant gram-negative bacteria have been described to be pan-drug resistant, implying a state devoid of alternative antibiotic therapeutic options. This review describes the evolution of antibiotic resistance to plasmid mediated colistin resistance, and discusses the potential role of high-throughput sequencing technologies, genomics and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antimicrobial resistance as a whole.

scholarly journals Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

2020 ◽  
Vol 38 (S1) ◽  
pp. 72-90 ◽  
Author(s):  
Niels Nijsingh ◽  
Christian Munthe ◽  
Anna Lindblom ◽  
Christina Åhrén
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Large Scale ◽  
Population Level ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
Screening Programs ◽  
Scale Population ◽  
Current Screening

AbstractEffectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention’s effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised.

scholarly journals Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 37 ◽  
Author(s):  
Emily M. Eichenberger ◽  
Joshua T. Thaden
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mechanisms ◽  
Individual Treatment ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Mechanisms Of Resistance ◽  
Gram Negative ◽  
Treatment Practices ◽  
Extensively Drug Resistant ◽  
Global Epidemiology

Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of large sets of clinical bacterial isolates has greatly expanded our understanding of how antibiotic resistance develops and transmits among bacteria and between patients. Diverse mechanisms of resistance, including antibiotic degradation, antibiotic target modification, and modulation of permeability through the bacterial membrane have been demonstrated. These fundamental insights into the mechanisms of gram-negative antibiotic resistance have influenced the development of novel antibiotics and treatment practices in highly resistant infections. Here, we review the mechanisms and global epidemiology of antibiotic resistance in some of the most clinically important resistance phenotypes, including carbapenem resistant Enterobacteriaceae, extensively drug resistant (XDR) Pseudomonas aeruginosa, and XDR Acinetobacter baumannii. Understanding the resistance mechanisms and epidemiology of these pathogens is critical for the development of novel antibacterials and for individual treatment decisions, which often involve alternatives to β-lactam antibiotics.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.

scholarly journals Rationally designed foldameric adjuvants enhance antibiotic efficacy via promoting membrane hyperpolarization

2021 ◽  
Author(s):  
Kaushik Nath Bhaumik ◽  
Anasztázia Hetényi ◽  
Gábor Olajos ◽  
Ana Martins ◽  
Réka Spohn ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Membrane Hyperpolarization ◽  
Gram Negative ◽  
Low Concentrations ◽  
Antibiotic Efficacy

Antimicrobial foldamers reduce the antibiotic resistance in multi-drug resistant Gram-negative bacteria. They hyperpolarize the membrane at low concentrations by acting as selective ionophores, enhancing the GHK-potential across the membrane.

scholarly journals 1206. Risk Factors of Antibiotic Resistance in E. coli Isolated from the MAL-ED Birth Cohort Study in Rural Tanzania

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S365-S366 ◽  
Author(s):  
Molly Fleece ◽  
Rosemary Nshama ◽  
Thomas Walongo ◽  
Jean Gratz ◽  
James Platts-Mills ◽  
...  
Keyword(s):  
Risk Factors ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Cohort Study ◽  
Birth Cohort Study ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Gram Negative ◽  
E Coli ◽  
Rural Tanzania

Abstract Background The emergence and spread of antimicrobial resistance is a serious global public health crisis. Drug-resistant Gram-negative bacteria, like Escherichia coli, are particularly concerning given their significant morbidity and mortality. Despite the increasing prevalence of drug-resistant Gram-negative bacteria worldwide, there are significant knowledge gaps in low resource countries. We aimed to characterize the prevalence, phenotypes, and risk factors of drug-resistant E. coli carriage in children up to age 5 from stool collected in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study in rural Tanzania. Methods Two hundred sixty-two children were enrolled in the MAL-ED Tanzania site. We randomly selected 100 children who had E. coli specimens archived every 6 months through 60 months. Up to five lactose-fermenting colonies were selected from growth on MacConkey agar. Drug susceptibility testing of 18 antibiotics was performed by disk diffusion. CLSI interpretive criteria were used for determination of resistance. Generalized estimating equations were used to create a multivariate Poisson regression model for drug resistance risk factors. Results Eight hundred twenty-three E. coli specimens were available for testing. The highest rates of resistance were to ampicillin, cefazolin, and cotrimoxazole, respectively. No carbapenem resistance was found. 1.8% met criteria for extended-spectrum β-lactamase production based on combination disk testing. 696 (84.6%) specimens met criteria for multi-drug resistance (nonsusceptible to at least 1 drug in at least three drug categories). In terms of dynamic risk factors, there was no association between antibiotic use or episodes of diarrhea and antibiotic resistance. For static risk factors, there was an association between higher income and increased antibiotic resistance. Conclusion Antibiotic resistance carriage is an under recognized problem in this setting. Resistance rates at 6 months of age are higher than expected, with surprisingly little variance explained by individual-level risk factors for resistance in this community. Disclosures All authors: No reported disclosures.

Extended Spectrum Beta Lactamase (ESBL), bla TEM,bla SHVand bla CTX-M,resistance genes in Community and Healthcare Associated Gram Negative Bacteria from Osun State, Nigeria

2020 ◽  
Vol 20 ◽  
Author(s):  
Ganiyat Shitta ◽  
Olufunmilola Makanjuola ◽  
Olusolabomi Adefioye ◽  
Olugbenga Adekunle Olowe
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Multiple Antibiotic Resistance ◽  
Esbl Production ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Healthcare Associated ◽  
Esbl Producers

Background: Extended Spectrum Beta Lactamase (ESBL) production in gram negative bacteria confers multiple antibiotic resistance, adversely affecting antimicrobial therapy in infected individuals. ESBLs result from mutations in β-lactamases encoded mainly by the bla TEM,bla SHVand bla CTX-Mgenes. The prevalence of ESBL producing bacteria has been on the increase globally especially its upsurge among isolates from community-acquired infections. Aim: To determine ESBL prevalence and identify ESBL genes among clinical isolates in Osun State, Nigeria. Material and Methods: A cross-sectional study was carried out from August 2016 –July 2017 in Osun State, Nigeria. Three hundred and sixty Gram negative bacteria recovered from clinical samples obtained from both community and healthcare associated infections were tested. They included147 Escherichia coli(40.8%), 116 Klebsiella spp(32.2%), 44 Pseudomo-nas aeruginosa(12.2%) and23 Proteus vulgaris (6.4%) isolates. Others were Acinetobacter baumannii, Serratia rubidae, Citrobacter spp, Enterobacter spp and Salmonella typhi. Disk diffusion antibiotic susceptibility testing was carried out, isolates were screened for ESBL production and confirmed using standard laboratory procedures. ESBLs resistance genes were identified by Polymerase Chain Reaction (PCR). Results: All isolates demonstrated multiple antibiotic resistance. Resistance to ampicillin, amoxicillin with clavulanate and erythromycin was 100%, whereas resistance to Imipenem was very low (5.0%). : Overall prevalence of ESBL producers was 41.4% with Klebsiellaspp as the highest ESBL producing Enterobacteriacaea. ESBL producers were more prevalent among the hospital pathogens than community pathogens, 58% vs 29.5% (p=0.003). ESBL genes were detected in all ESBL producers with the blaCTX-Mgene predominating (47.0%) followed by blaTEM(30.9%) and blaSHVgene was the least, 22.1%. The blaCTX-Mgene was also the most prevalent in the healthcare pathogens (62%) but it accounted for only 25% in those of community origin. Conclusion: A high prevalence of ESBL producing gram negative organisms occurs both in healthcare and in the community in our environment with the CTX-M variant predominating. Efforts to control spread of these pathogens should be addressed.

scholarly journals A Simple Method for Assessment of MDR Bacteria for Over-Expressed Efflux Pumps

2013 ◽  
Vol 7 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Marta Martins ◽  
Matthew P McCusker ◽  
Miguel Viveiros ◽  
Isabel Couto ◽  
Séamus Fanning ◽  
...  
Keyword(s):  
Ethidium Bromide ◽  
Efflux Pump ◽  
Efflux Pumps ◽  
Outer Cell ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Topoisomerase Iv ◽  
Simple Method ◽  
Gram Negative ◽  
Over Expression

It is known that bacteria showing a multi-drug resistance phenotype use several mechanisms to overcome the action of antibiotics. As a result, this phenotype can be a result of several mechanisms or a combination of thereof. The main mechanisms of antibiotic resistance are: mutations in target genes (such as DNA gyrase and topoisomerase IV); over-expression of efflux pumps; changes in the cell envelope; down regulation of membrane porins, and modified lipopolysaccharide component of the outer cell membrane (in the case of Gram-negative bacteria). In addition, adaptation to the environment, such as quorum sensing and biofilm formation can also contribute to bacterial persistence. Due to the rapid emergence and spread of bacterial isolates showing resistance to several classes of antibiotics, methods that can rapidly and efficiently identify isolates whose resistance is due to active efflux have been developed. However, there is still a need for faster and more accurate methodologies. Conventional methods that evaluate bacterial efflux pump activity in liquid systems are available. However, these methods usually use common efflux pump substrates, such as ethidium bromide or radioactive antibiotics and therefore, require specialized instrumentation, which is not available in all laboratories. In this review, we will report the results obtained with the Ethidium Bromide-agar Cartwheel method. This is an easy, instrument-free, agar based method that has been modified to afford the simultaneous evaluation of as many as twelve bacterial strains. Due to its simplicity it can be applied to large collections of bacteria to rapidly screen for multi-drug resistant isolates that show an over-expression of their efflux systems. The principle of the method is simple and relies on the ability of the bacteria to expel a fluorescent molecule that is substrate for most efflux pumps, ethidium bromide. In this approach, the higher the concentration of ethidium bromide required to produce fluorescence of the bacterial mass, the greater the efflux capacity of the bacterial cells. We have tested and applied this method to a large number of Gram-positive and Gram-negative bacteria to detect efflux activity among these multi-drug resistant isolates. The presumptive efflux activity detected by the Ethidium Bromide-agar Cartwheel method was subsequently confirmed by the determination of the minimum inhibitory concentration for several antibiotics in the presence and absence of known efflux pump inhibitors.

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