Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers

2016 ◽  
Vol 1 (11) ◽  
Author(s):  
Shu J. Lam ◽  
Neil M. O'Brien-Simpson ◽  
Namfon Pantarat ◽  
Adrian Sulistio ◽  
Edgar H. H. Wong ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Peptide Polymers

scholarly journals “Clicking” an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability

2020 ◽  
Vol 21 (17) ◽  
pp. 6174
Author(s):  
Ana Gomes ◽  
Lucinda J. Bessa ◽  
Patrícia Correia ◽  
Iva Fernandes ◽  
Ricardo Ferraz ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Ionic Liquids ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Peptide ◽  
Clinical Isolate ◽  
Bioactive Peptides ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Improved Stability

A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via “click” chemistry, and found to retain the parent peptide’s activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.

scholarly journals A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  
Keyword(s):  
Public Health ◽  
Chemical Biology ◽  
Multidrug Resistant ◽  
Computational Approach ◽  
Gram Negative Bacteria ◽  
Global Public Health ◽  
Gram Negative ◽  
Life Threatening ◽  
New Generation ◽  
Novel Antibiotics

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.

scholarly journals Structurally nanoengineered antimicrobial peptide polymers: design, synthesis and biomedical applications

2021 ◽  
Vol 37 (8) ◽  
Author(s):  
Ronisha Ramamurthy ◽  
Chetan H. Mehta ◽  
Usha Y. Nayak
Keyword(s):  
Health Care ◽  
Antimicrobial Peptide ◽  
Biomedical Applications ◽  
Multidrug Resistant ◽  
Chronic Infections ◽  
Synthesis Mechanism ◽  
Design Synthesis ◽  
Global Health Care ◽  
Conventional Antibiotics ◽  
Peptide Polymers

Abstract Antimicrobial resistance not only increases the contagiousness of infectious diseases but also a threat for the future as it is one of the health care concern around the globe. Conventional antibiotics are unsuccessful in combating chronic infections caused by multidrug-resistant (MDR) bacteria, therefore it is important to design and develop novel strategies to tackle this problems. Among various novel strategies, Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPPs) have been introduced in recent years to overcome this global health care issue and they are found to be more efficient in their performance. Many facile methods are adapted to synthesize complex SNAPPs with required dimensions and unique functionalities. Their unique characteristics and remarkable properties have been exploited for their immense applications in various fields including biomedicine, targeting therapies, gene delivery, bioimaging, and many more. This review article deals with its background, design, synthesis, mechanism of action, and wider applications in various fields of SNAPPs. Graphic abstract

scholarly journals Outcomes and Risk Factors in Prosthetic Joint Infections by multidrug-resistant Gram-negative Bacteria: A Retrospective Cohort Study

Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 340
Author(s):  
Raquel Bandeira da Silva ◽  
Mauro José Salles
Keyword(s):  
Risk Factors ◽  
Treatment Failure ◽  
Treatment Outcomes ◽  
Revision Arthroplasty ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Postoperative Hematoma ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

scholarly journals 832. Assessment of Risk Factors Associated with Wide-resistance Gram-negative Bacteria Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S457-S457
Author(s):  
Henry Pablo Lopes Campos e Reis ◽  
Ana Beatriz Ferreira Rodrigues ◽  
Julio César Castro Silva ◽  
Lia Pinheiro de Lima ◽  
Talita Lima Quinaher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Univariate Analysis ◽  
Multidrug Resistant ◽  
University Hospital ◽  
Gram Negative Bacteria ◽  
Multiresistant Pathogens ◽  
Gram Negative ◽  
Contact Isolation ◽  
Bladder Catheter

Abstract Background Enterobacteria and multidrug-resistant non-fermenting Gram-negative bacilli present a challenge in the management of invasive infections, leading to mortality rates due to their limited therapeutic arsenal. The objective of this work was to analyze risk factors that may be associated with these infections, for a better situational mapping and assertive decision-making in a university hospital in Brazil. Methods The study was conducted between January and September 2019, with 167 patients in contact isolation at a university hospital in Brazil. Potential outcome-related variables for wide-resistance Gram-negative bacteria (BGN) infections were evaluated. Risk factors were identified from univariate statistical analysis using Fisher’s test. Results 51 (30.5%) out of 167 patients in contact isolation evolved with wide-resistance BGN infection. Risk factors in univariate analysis were age, hospital unit and previous use of invasive devices. Patients aged up to 59 years were more likely to progress to infection than those aged over 60 years (p 0.0274, OR 2.2, 95% CI 1.1-4.5). Those admitted to the oncohematology (p &lt; 0.001, OR 32.5, Cl 9.1-116.3) and intensive care unit (p &lt; 0.001, OR 28.0, Cl 3.5-225.9) units were more likely to develop this type of infection. The least likely were those admitted to a kidney transplant unit (p 0.0034, OR 15.33, Cl 1.8-131.0). Prior use of mechanical ventilation (p 0.0058, OR 12.2, Cl 2.0-76.1) and delayed bladder catheter (p 0.0266, OR 5.0, Cl 1.2-20.1) in patients with respiratory and urinary tract infection, respectively, were also reported as risk factors related to these infections. The gender of the patients was not significant for the study. Conclusion This study determined that variables such as age, hospitalization unit, use of mechanical ventilation and delayed bladder catheter could be considered important risk factors in triggering the infectious process by wide-resistant gram-negative bacteria. Thus, the analysis of these factors becomes a great foundation to prevent the development of multiresistant pathogens through prevention strategies, prophylaxis management and more targeted empirical therapies. Disclosures All Authors: No reported disclosures

scholarly journals Multidrug-Resistant Gram-Negative Bacteria in Hematology and Oncology

2014 ◽  
Vol 35 (9) ◽  
pp. 1203-1204
Author(s):  
Enrico Schalk ◽  
Jacqueline Färber ◽  
Thomas Fischer
Keyword(s):  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative
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