scholarly journals Ultrasensitive Label-Free Detection of Unamplified Multidrug-Resistance Bacteria Genes with a Bimodal Waveguide Interferometric Biosensor

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 845
Author(s):  
Jesús Maldonado ◽  
Ana Belén González-Guerrero ◽  
Adrián Fernández-Gavela ◽  
Juan José González-López ◽  
Laura M. Lechuga

Infections by multidrug-resistant bacteria are becoming a major healthcare emergence with millions of reported cases every year and an increasing incidence of deaths. An advanced diagnostic platform able to directly detect and identify antimicrobial resistance in a faster way than conventional techniques could help in the adoption of early and accurate therapeutic interventions, limiting the actual negative impact on patient outcomes. With this objective, we have developed a new biosensor methodology using an ultrasensitive nanophotonic bimodal waveguide interferometer (BiMW), which allows a rapid and direct detection, without amplification, of two prevalent and clinically relevant Gram-negative antimicrobial resistance encoding sequences: the extended-spectrum betalactamase-encoding gene blaCTX-M-15 and the carbapenemase-encoding gene blaNDM-5 We demonstrate the extreme sensitivity and specificity of our biosensor methodology for the detection of both gene sequences. Our results show that the BiMW biosensor can be employed as an ultrasensitive (attomolar level) and specific diagnostic tool for rapidly (less than 30 min) identifying drug resistance. The BiMW nanobiosensor holds great promise as a powerful tool for the control and management of healthcare-associated infections by multidrug-resistant bacteria.

2020 ◽  
Vol 8 (5) ◽  
pp. 639 ◽  
Author(s):  
Alexis Simons ◽  
Kamel Alhanout ◽  
Raphaël E. Duval

Currently, the emergence and ongoing dissemination of antimicrobial resistance among bacteria are critical health and economic issue, leading to increased rates of morbidity and mortality related to bacterial infections. Research and development for new antimicrobial agents is currently needed to overcome this problem. Among the different approaches studied, bacteriocins seem to be a promising possibility. These molecules are peptides naturally synthesized by ribosomes, produced by both Gram-positive bacteria (GPB) and Gram-negative bacteria (GNB), which will allow these bacteriocin producers to survive in highly competitive polymicrobial environment. Bacteriocins exhibit antimicrobial activity with variable spectrum depending on the peptide, which may target several bacteria. Already used in some areas such as agro-food, bacteriocins may be considered as interesting candidates for further development as antimicrobial agents used in health contexts, particularly considering the issue of antimicrobial resistance. The aim of this review is to present an updated global report on the biology of bacteriocins produced by GPB and GNB, as well as their antibacterial activity against relevant bacterial pathogens, and especially against multidrug-resistant bacteria.


Author(s):  
Chakraborty Tamalika ◽  
Shaw Ranjana ◽  
Chatterjee Dr. Sumana ◽  
Datta Dr. Lopamudra ◽  
Sengupta Dr. Abhijit

2015 ◽  
Vol 59 (4) ◽  
pp. 2315-2327 ◽  
Author(s):  
Jürgen B. Bulitta ◽  
Neang S. Ly ◽  
Cornelia B. Landersdorfer ◽  
Nicholin A. Wanigaratne ◽  
Tony Velkov ◽  
...  

ABSTRACTBacterial resistance is among the most serious threats to human health globally, and many bacterial isolates have emerged that are resistant to all antibiotics in monotherapy. Aminoglycosides are often used in combination therapies against severe infections by multidrug-resistant bacteria. However, models quantifying different antibacterial effects of aminoglycosides are lacking. While the mode of aminoglycoside action on protein synthesis has often been studied, their disruptive action on the outer membrane of Gram-negative bacteria remains poorly characterized. Here, we developed a novel quantitative model for these two mechanisms of aminoglycoside action, phenotypic tolerance at high bacterial densities, and adaptive bacterial resistance in response to an aminoglycoside (tobramycin) against threePseudomonas aeruginosastrains. At low-intermediate tobramycin concentrations (<4 mg/liter), bacterial killing due to the effect on protein synthesis was most important, whereas disruption of the outer membrane was the predominant killing mechanism at higher tobramycin concentrations (≥8 mg/liter). The extent of killing was comparable across all inocula; however, the rate of bacterial killing and growth was substantially lower at the 108.9CFU/ml inoculum than that at the lower inocula. At 1 to 4 mg/liter tobramycin for strain PAO1-RH, there was a 0.5- to 6-h lag time of killing that was modeled via the time to synthesize hypothetical lethal protein(s). Disruption of the outer bacterial membrane by tobramycin may be critical to enhance the target site penetration of antibiotics used in synergistic combinations with aminoglycosides and thereby combat multidrug-resistant bacteria. The two mechanisms of aminoglycoside action and the new quantitative model hold great promise to rationally design novel, synergistic aminoglycoside combination dosage regimens.


2021 ◽  
Author(s):  
Zhou Chen ◽  
Yue Hu ◽  
Xinggang Mao ◽  
Dan Nie ◽  
Hui Zhao ◽  
...  

Abstract Background: Outbreaks of infection due to multidrug-resistant bacteria, especially gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by multidrug-resistant bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity.Results: Here, we designed a series of dendritic poly-peptides (DPP1 to DPP12) to encapsulate ASOs to form DSPE-mPEG2000 decorated ASOs/DPP nanoparticles (DP-AD1 to DP-AD12) and observed that amphipathic DP-AD2, 3, 7 or 8 with a positive charge ≥ 8 showed great efficiency to deliver ASOs into bacteria, but only the two histidine residues contained DP-AD7 and DP-AD8 significantly inhibited the bacterial growth and the targeted gene expression of tested bacteria in vitro. DP-AD7anti-acpP remarkably increased the survival rate of septic mice infected by ESBLs-E. coli, exhibiting strong antibacterial effects in vivo.Conclusions: For the first time, we designed DPP as a potent carrier to deliver ASOs for combating MDR bacteria and demonstrated essential features, namely, amphipathicity, 8–10 positive charges, and 2 histidine residues, that are required for efficient DPP based delivery, and provide a novel approach for the development and research of the antisense antibacterial strategy.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S108-S109
Author(s):  
Margaret Lubwama ◽  
Scott Adams ◽  
Catherine Muwonge ◽  
Freddie Bwanga ◽  
David Kateete ◽  
...  

Abstract Background Cancer patients are at risk of developing severe infections. Empiric management of infections is complicated by emerging antimicrobial resistance and changing local epidemiology of organisms. We sought to determine predominant species causing bacteremia, their antimicrobial resistance profiles, and their contribution to mortality among hematologic cancer patients with febrile neutropenia at the Uganda Cancer Institute. Methods Blood drawn from participants during a febrile neutropenic episode (FNE; fever ≥37.5°C and neutrophil count ≤1,000 cells/µL) was cultured in the BACTEC 9120 blood culture system. Bacteria from positive cultures were identified biochemically. Antimicrobial susceptibility testing was performed with the disc diffusion method. Logistic regression and proportional hazards regression were applied to estimate associations between participant characteristics and FNE, bacteremia, and mortality. Results Of 246 participants, 74 (30%) had an FNE. During the first FNE, 6/21 (29%) participants with acute lymphocytic leukemia (ALL) developed bacteremia compared with 16/31 (52%) with acute myeloid leukemia (AML) (OR 2.22 (0.65, 7.4)). AML patients were specifically at higher risk of Gram-negative bacteremia (OR 4.59 (1.09, 19.3). Of the 41 aerobic bacteria isolated, 32 (78%) were Gram-negative, the most common being Klebsiella pneumoniae (11; 34%). Seventeen (53%) of the Gram-negative bacteria displayed the extended spectrum β lactamase phenotype and 5 (16%) were resistant to carbapenems. One of the eight Enterococcus species was vancomycin resistant. Overall survival among patients with FNE was 54% at 30 days and 19% at 100 days. Bacteremia was associated with higher mortality within 30 days (HR 2.1 (0.99, 4.45)) and 100 days (31% vs.10%; HR 2.23 (1.09, 4.59)). Conclusion Multidrug-resistant bacteria are the main cause of bacteremia and increase mortality in febrile neutropenic hematologic cancer patients at the UCI. Enhanced microbial surveillance, infection control and antimicrobial stewardship programs are needed to guide therapy and address emerging antimicrobial resistance at our institution. Disclosures All authors: No reported disclosures.


Pharmacy ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 92 ◽  
Author(s):  
Shazia Jamshed ◽  
Fadzlan Padzil ◽  
Siti Shamsudin ◽  
Siti Bux ◽  
Abdul Jamaluddin ◽  
...  

The increase in antibiotic resistance has frequently been linked to unrestrained antibiotic dispensing. This review was conducted to mainly assess the perception and attitudes of community pharmacists towards antibiotic dispensing. This scoping review was performed between June 2016 and September 2016 to identify published studies related to the perception and attitudes of community pharmacists towards antibiotic dispensing. The combination of terms such as ‘antibiotic dispensing’, ‘antimicrobial resistance’, ‘community pharmacy’, and ‘community pharmacists’ were searched in electronic databases such as PubMed, ProQuest, Google Scholar, and Science Direct. Only published articles within the last 12 years were included. A total of 13 studies were identified. In general, community pharmacists have good awareness and knowledge of antibiotic dispensing. However, the majority of them are still selling antibiotics to their customers and/or patients for unjustified reasons. The community pharmacists seem well aware of the antimicrobial resistance crisis and considered it a significant health issue. However, many embraced the concept that dispensing antibiotics without medical prescription (DAwMP) can be one of the key features in the dissemination of multidrug resistant bacteria.


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