scholarly journals Flavonoids as Inhibitors of Bacterial Efflux Pumps

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6904
Author(s):  
Martin Waditzer ◽  
Franz Bucar
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Plant Secondary Metabolites ◽  
Herbal Medicines ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Plant Constituents ◽  
Kaempferol Glycosides

Flavonoids are widely occurring secondary plant constituents, and are abundant in vegetable and fruit diets as well as herbal medicines. Therapeutic treatment options for bacterial infections are limited due to the spread of antimicrobial resistances. Hence, in a number of studies during the last few years, different classes of plant secondary metabolites as resistance-modifying agents have been carried out. In this review, we present the role of flavonoids as inhibitors of bacterial efflux pumps. Active compounds could be identified in the subclasses of chalcones, flavan-3-ols, flavanones, flavones, flavonols, flavonolignans and isoflavones; by far the majority of compounds were aglycones, although some glycosides like kaempferol glycosides with p-coumaroyl acylation showed remarkable results. Staphylococcus aureus NorA pump was the focus of many studies, followed by mycobacteria, whereas Gram-negative bacteria are still under-investigated.

scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

scholarly journals Dissemination of Carbapenem-resistance and Plasmids-encoding Carbapenemases in Gram-negative Bacteria Isolated from India

2020 ◽  
Author(s):  
Prasanth Manohar ◽  
Sebastian Leptihn ◽  
Bruno S. Lopes ◽  
Nachimuthu Ramesh
Keyword(s):  
Tamil Nadu ◽  
Treatment Options ◽  
Public Health Problem ◽  
Carbapenem Resistance ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
E Coli ◽  
Diagnostic Center ◽  
Lactamase Gene

AbstractCarbapenem resistance in Gram-negative bacteria is an ongoing public-health problem of global dimensions leaving very few treatment options for severely infected patients. This study focuses on the dissemination of plasmid-borne carbapenemase genes in Gram-negative bacteria in Tamil Nadu, India. A total of 151 non-repetitive isolates belonging to 11 genera were collected from a diagnostic center in Tamil Nadu. E. coli (n=57) isolates were classified as, Enteropathogenic (n=12), Enteroaggregative (n=9), Enterohemorrhagic (n=8), Enterotoxigenic (n=3), Enteroinvasive (n=1) and unclassified E. coli (n=24). Of the 45 Klebsiella species, 14 were K1 whereas 11 were K2 serotype and in 20 Klebsiella serotype could not be determined. Other isolates (n=49) consisted of P. aeruginosa, S. typhi, E. cloacae, A. baumannii, S. marcescens, A. xylosoxidans, P. mirabilis and E. meningoseptica. Of the 151 isolates, 71% (n=107) and 68% (n=103) were found to be resistant to meropenem and imipenem respectively. The most prevalent beta-lactamase gene was blaNDM-1 (21%, 12/57) followed by blaOXA-181 (16%, 9/57), blaGES-9 (n=8), blaOXA-23 (n=7), blaIMP-1 (n=3), blaGES-1 (n=11) and blaOXA-51 (n=9). The unusual presence of blaOXA-23 was seen in E. coli (n=4), and blaOXA-23 and blaOXA-51 (IncA/C) in K. pneumoniae (n=3). Plasmid incompatibility (inc/rep) typing results showed that the plasmids carrying resistance genes (n=11) belonged to IncX, IncA/C, IncFIA-FIB and IncFIIA groups. E. coli and K. pneumoniae were able to transfer plasmid-borne carbapenemase via conjugation. This study highlights the prevalence of carbapenem resistance and the acquisition of plasmid-borne carbapenemase genes in Gram-negative bacteria highlighting the role of plasmid transfer in disseminating resistance.

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.

Antimicrobial Resistance in the Intensive Care Unit

2016 ◽  
Vol 32 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Shawn H. MacVane
Keyword(s):  
Intensive Care ◽  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Hospital Costs ◽  
High Morbidity ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Negative Organisms

Bacterial infections are a frequent cause of hospitalization, and nosocomial infections are an increasingly common condition, particularly within the acute/critical care setting. Infection control practices and new antimicrobial development have primarily focused on gram-positive bacteria; however, in recent years, the incidence of infections caused by gram-negative bacteria has risen considerably in intensive care units. Infections caused by multidrug-resistant (MDR) gram-negative organisms are associated with high morbidity and mortality, with significant direct and indirect costs resulting from prolonged hospitalizations due to antibiotic treatment failures. Of particular concern is the increasing prevalence of antimicrobial resistance to β-lactam antibiotics (including carbapenems) among Pseudomonas aeruginosa and Acinetobacter baumannii and, recently, among pathogens of the Enterobacteriaceae family. Treatment options for infections caused by these pathogens are limited. Antimicrobial stewardship programs focus on optimizing the appropriate use of currently available antimicrobial agents with the goals of improving outcomes for patients with infections caused by MDR gram-negative organisms, slowing the progression of antimicrobial resistance, and reducing hospital costs. Newly approved treatment options are available, such as β-lactam/β-lactamase inhibitor combinations, which significantly extend the armamentarium against MDR gram-negative bacteria.

RND efflux pumps in Gram-negative bacteria; regulation, structure and role in antibiotic resistance

2020 ◽  
Vol 15 (2) ◽  
pp. 143-157 ◽  
Author(s):  
Abigail L Colclough ◽  
Ilyas Alav ◽  
Emily E Whittle ◽  
Hannah L Pugh ◽  
Elizabeth M Darby ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Bacterial Cells ◽  
Intrinsic Resistance ◽  
Gram Negative ◽  
New Information ◽  
Rnd Efflux Pumps ◽  
Gram Negative Organisms

Rresistance-nodulation-division (RND) efflux pumps in Gram-negative bacteria remove multiple, structurally distinct classes of antimicrobials from inside bacterial cells therefore directly contributing to multidrug resistance. There is also emerging evidence that many other mechanisms of antibiotic resistance rely on the intrinsic resistance conferred by RND efflux. In addition to their role in antibiotic resistance, new information has become available about the natural role of RND pumps including their established role in virulence of many Gram-negative organisms. This review also discusses the recent advances in understanding the regulation and structure of RND efflux pumps.

scholarly journals Clinical Treatment Options for Carbapenem-resistant Gram-negative Infections in China: a Single Centre Real-world Experience

2021 ◽  
Author(s):  
Ruanmei Sheng ◽  
Xuemin Wang ◽  
Yanqiang Hou ◽  
Jun Liu ◽  
Zhiwen Yang
Keyword(s):  
Success Rate ◽  
Bacterial Infections ◽  
Clinical Success ◽  
Treatment Options ◽  
Clinical Success Rate ◽  
Gram Negative Bacteria ◽  
Single Centre ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Clinical Strategies

Abstract Carbapenem-resistant gram-negative bacteria constitute a serious threat to public health worldwide. However, as a result of the complexities of clinical therapy, antibiotic options against carbapenem-resistant pathogens have not yet been fully standardized. Here, we conducted a retrospective study in 65,000 inpatients over a 2-year period that involved a total of 86 patients from whom carbapenem-resistant gram-negative bacteria were isolated. Monotherapy using trimethoprim/ sulfamethoxazole, amikacin, meropenem, and/or doxycycline in our hospital exhibited a clinical success rate of 83.3% for carbapenem-resistant Klebsiella pneumoniae, monotherapy using moxifloxacin, piperacillin/tazobactam, cefepime, and/or ceftazidime for carbapenem-resistant Pseudomonas aeruginosa exhibited a clinical success rate of 77.7%, and monotherapy using cefoperazone/sulbactam or combination therapy with tigecycline and cefoperazone/sulbactam for carbapenem-resistant Acinetobacter baumannii exhibited a clinical success rate of 62.1%. Our findings highlight the clinical strategies used in our hospital to successfully treat carbapenem-resistant gram-negative bacterial infections.

Role of lipopolysaccharides in potential applications of nanocarrier systems

2021 ◽  
Vol 27 ◽  
Author(s):  
Pravin Shende ◽  
Shubham Gupta
Keyword(s):  
Bacterial Infections ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Surrounding Environment ◽  
Recent Developments ◽  
Potential Applications ◽  
Immune Stimulants ◽  
Therapeutic Properties ◽  
Immunogenic Response

Background: Lipopolysaccharides (LPS) are considered the main molecular component in the outer membrane of gram-negative bacteria. The LPS molecule in the bacterial cell wall acts as a primary physical barrier and protects gram-negative bacteria from the surrounding environment. LPS (endotoxins) show immunomodulatory therapeutic properties as well as toxicity to the host cell, whereas potential applications encompass. Objective: This review article aims to describe the recent developments of lipopolysaccharides in nanocarrier systems for various applications such as vaccination, cancer chemotherapy and immune stimulants action. Different nanocarriers like cubosomes, niosomes, dendrimers and metal nanoparticles used in the delivery of actives are employed to decorate lipopolysaccharide molecules superficially. Methods: A narrative review of all the relevant papers known to the author was conducted. Conclusion: Commercially available lipid nanoparticles contribute to many advances as promising nanocarriers in cancer therapy and are used as a vaccine adjuvant by improving the immune response due to their properties such as size, shape, biocompatibility, and biodegradability. Whereas lipopolysaccharide-decorated nanoparticles change the host's tolerability and increase the effectiveness of molecule in cancer immunotherapy. These nanoconjugate systems enhance overall immunogenic response and effectiveness in vaccine immunotherapy and targeted therapy, not only limited to humans application but also for poultry and aquaculture. Newer opportunities using lipopolysaccharides for the treatment and management of diseases with unique characteristics like the presence of lipoprotein that act as an alternative for bacterial infections over conventional dosage forms.

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.

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