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 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 Antibiotic resistance pattern of bacterial isolates retrieved from febrile neutropenic patients with hematological disorders

2020 ◽  
Author(s):  
Gayatri Prajapati ◽  
Bishesh Sharma Poudyal ◽  
Krishna Kumar Maharjan ◽  
Sunita Prajapati ◽  
Janak Raj Dhungana
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistance ◽  
Effective Treatment ◽  
Resistance Pattern ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Hematological Disorders ◽  
Gram Positive Bacteria ◽  
Neutropenic Patients

Abstract Background Antibiotic resistance is nowadays becoming a threat in the treatment of immunosuppressed patients. The aim of this study was to find out the antibiotic resistance pattern of bacteria isolated from febrile neutropenic patients with hematological disorders so that it would help to select the empirical antibiotic for prompt effective treatment of the febrile neutropenic patients. Methods A cross-sectional descriptive study was conducted at a tertiary care hospital of Nepal from October 2018 to November 2019. Blood was drawn aseptically in blood culture bottles. The bacteria were identified by standard microbiological methods with observation of colony morphology, gram staining and biochemical tests of bacteria. The antibiotic susceptibility tests were done by Kirby Bauer disc diffusion method. Extended Spectrum Beta Lactamase (ESBL) and Metallo Beta Lactamase (MBL) producers, and Methicillin Resistant Staphylococcus aureus (MRSA) were detected by phenotypic methods. Results Of the total 214 blood samples, 33.9% (71) yielded the bacterial growth. Gram negative bacteria were isolated from 23.8% of total samples and Gram-positive bacteria were isolated from 9.3% of the total samples. The Gram negative bacteria isolated were Escherichia coli (7.9%), Klebsiella pneumoniae (4.7%), Citrobacter spp. (4.7%), Acinetobacter spp. (3.7%) and Pseudomonas aeruginosa (2.8%). The Gram-positive bacteria isolated were Staphylococcus aureus (5.6%), Coagulase Negative Staphylococcus (2.3%) and Enterococcus spp. (1.4%). About 66.7% of the total Gram-negative bacteria isolated and 50% of the total Gram-positive bacteria were MDR (Multidrug-resistant). About 19.6% of the total Gram-negative bacteria were ESBL producers and 19.6% of them were MBL producers. About 41.6% of Staphylococcus aureus isolated were MRSA (Methicillin Resistant S. aureus). In our institution, piperacillin-tazobactam is the preferred first choice empirical antibiotic. But 58.8% of the Gram negative organisms were found to be resistant towards piperacillin-tazobactam. Hence there is a prompt necessity to switch to another antibiotic with high sensitivity for effective treatment of the febrile neutropenic patients in our institution. Conclusion Antibiotic surveillance data should be evaluated periodically to select the empirical therapeutic antibiotic for effective treatment of febrile neutropenic patients.

scholarly journals Investigation of gating in outer membrane porins provides new perspectives on antibiotic resistance mechanisms

2021 ◽  
Author(s):  
Archit Kumar Vasan ◽  
Nandan Haloi ◽  
Rebecca Joy Ulrich ◽  
Mary Elizabeth Metcalf ◽  
Po-Chao Wen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Outer Membrane ◽  
Large Scale ◽  
Dynamic Equilibrium ◽  
Resistance Mechanisms ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Scale Motion

AbstractGram-negative bacteria pose a serious public health concern, primarily due to a higher frequency of antibiotic resistance conferred to them as a result of low permeability of their outer membrane (OM). Antibiotics capable of traversing the OM typically permeate through OM porins; thus, understanding the permeation properties of these porins is instrumental to the development of new antibiotics. A common macroscopic feature of many OM porins is their ability to transition between functionally distinct open and closed states that regulate transport properties and rate. To obtain a molecular basis for these processes, we performed tens of microseconds of molecular dynamics simulations of E. coli OM porin, OmpF. We observed that large-scale motion of the internal loop, L3, leads to widening and narrowing of the pore, suggesting its potential role in gating. Furthermore, Markov state analysis revealed multiple energetically stable conformations of L3 corresponding to open and closed states of the porin. Dynamics between these functional states occurs on the time scale of tens of microseconds and are mediated by the movement of highly conserved acidic residues of L3 to form H-bonds with opposing sides of the barrel wall of the pore. To validate our mechanism, we mutated key residues involved in the gating process that alter the H-bond pattern in the open/closed states and performed additional simulations. These mutations shifted the dynamic equilibrium of the pore towards open or closed states. Complementarily, the mutations favoring the open/closed states lead to increased/decreased accumulation of multiple antibiotics in our whole-cell accumulation assays. Notably, porins containing one of the mutations favoring the closed state has previously been found in antibiotic resistant bacterial strains. Overall, our 180 µs of simulation data (wild type and mutants) with concerted experiments suggests that regulation of the dynamic equilibrium between open and closed states of OM porins could be a mechanism by which Gram-negative bacteria acquire antibiotic resistance.

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.

Success and Challenges Associated with Large Scale Collaborative Surveillance for Carbapenemase Genes in Gram Negative Bacteria

2021 ◽  
Author(s):  
Sanchita Das ◽  
Karen Bush
Keyword(s):  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Large Scale ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Routine Laboratory ◽  
Significant Morbidity ◽  
Gram Negative ◽  
Surveillance Studies ◽  
The One

The emergence and spread of antimicrobial resistance, especially in Gram negative bacteria has led to significant morbidity and increased cost of healthcare. Large surveillance studies such as the one performed by the Antibiotic Resistance Laboratory Network are immensely valuable in understanding the scope of resistance mechanisms especially among carbapenemase producing Gram negative bacteria. However, the routine laboratory detection of carbapenemases in these bacteria remain challenging and require further optimization.

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.

Sign in / Sign up

Export Citation Format

Share Document