Abstract
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.
Highlights
Hospital-acquired or healthcare-associated infections (HAIs) refer to an infection that develops at least 48 h after the patient is admitted to a hospital [1]
In Europe, 3–10% of all hospitalizations in acute care hospitals (ACH) and long-term care facilities (LTCF) result in nosocomial infections, with the highest rates in surgical (7%) and intensive care units
1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS), the components for phosphate buffer saline (PBS; 10 mM phosphate, 2.9 mM KCl, 137 mM NaCl, pH 7.4), 0.5 M NaCl/Tris-EDTA buffer, and 1 mM MgCl2 were purchased from Sigma-Aldrich (Madrid, Spain)
Summary
Hospital-acquired or healthcare-associated infections (HAIs) refer to an infection that develops at least 48 h after the patient is admitted to a hospital [1]. These infections are caused during a prolonged stay at the hospital and are a major risk factor for serious health issues leading even to death [2]. 2016–2017 were Gram-negative bacteria, with Enterobacterales (38%) as the most prevalent, of which. Escherichia coli (16%) and Klebsiella pneumoniae (10%) were the most frequently found, followed by other non-Enterobacterales Gram-negative bacteria (14%), with Pseudomonas aeruginosa (8%) and Acinetobacter spp (3%) as the most commonly isolated species [4].
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