Nanomechanical sensor applied to blood culture pellets: a fast approach to determine the antibiotic susceptibility against agents of bloodstream infections

Stupar, Petar; Opota, Onya; Longo, Giovanni; Prod’hom, Guy; Dietler, Giovanni; Greub, Gilbert; Kasas, Sandor

doi:10.1016/j.cmi.2016.12.028

Cited by 57 publications

(57 citation statements)

References 23 publications

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“…We have observed that 40 min incubation time is sufficient to register the effect of the clarithromycin and erythromycin, and less than 20 min for ampicillin (Figure S3, Supporting Information). This result is in agreement with those previously reported with this device but using fast‐growing bacteria …”

Section: Resultssupporting

confidence: 94%

“…Before deposition, in order to promote bacterial attachment, the cantilevers were incubated with 10 µL of 0.5% glutaraldehyde for 10 min, rinsed with ultrapure water, dried, and then incubated with 10 µL of a high‐density bacterial suspension (OD 595 : 0.5 with 100 µL of suspension diluted in 1 mL of phosphate buffer saline). The cantilevers with adhered bacteria were inserted into the analysis chamber of a homemade nanomotion device to analyze their vibrational response in growth medium and upon exposure to antibiotics . For each tested condition, 40 min measurements of the cantilever oscillations were done at the room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow‐Growing Bacteria

Villalba

Stupar

Chomicki

et al. 2017

Small

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Infectious diseases are caused by pathogenic microorganisms and are often severe. Time to fully characterize an infectious agent after sampling and to find the right antibiotic and dose are important factors in the overall success of a patient's treatment. Previous results suggest that a nanomotion detection method could be a convenient tool for reducing antibiotic sensitivity characterization time to several hours. Here, the application of the method for slow-growing bacteria is demonstrated, taking Bordetella pertussis strains as a model. A low-cost nanomotion device is able to characterize B. pertussis sensitivity against specific antibiotics within several hours, instead of days, as it is still the case with conventional growth-based techniques. It can discriminate between resistant and susceptible B. pertussis strains, based on the changes of the sensor's signal before and after the antibiotic addition. Furthermore, minimum inhibitory and bactericidal concentrations of clinically applied antibiotics are compared using both techniques and the suggested similarity is discussed.

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Section: Resultssupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow‐Growing Bacteria

Villalba

Stupar

Chomicki

et al. 2017

Small

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“…Recently a nanomechanical method of detecting the viability of bacterial cells immobilized on soft cantilevers was reported by Longo et al [17][18][19][20] which has attracted much attention by virtue of its ability to detect AST within minutes. In the nanomechanical method a non-specific linker molecule was used to coat the cantilever surface with hundreds of bacterial cells, and the motion of the cantilever was monitored using a laser before and after the application of an antibiotic.…”

Section: Mainmentioning

confidence: 99%

Cantilever Sensors for Rapid Optical Antimicrobial Sensitivity Testing

Bennett

Pyne

McKendry

2019

Preprint

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Growing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST) which measures bacterial growth and is therefore hampered by slow time to result (~12-24 hours).Therefore new rapid phenotypic methods for AST are urgently needed. Nanomechanical cantilever sensors have recently shown promise for rapid AST but challenges of bacterial immobilization can lead to variable results. Herein a novel cantilever-based method is described for detecting phenotypic antibiotic resistance within ~45 minutes, capable of detecting single bacteria. This method does not require complex, variable bacterial immobilization, and instead uses the laser and detector system to detect single bacterial cells in media as they pass through the laser focus. This provides a simple read out of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), much faster than

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“…The high sensitivity of the nanosensor made it possible to differentiate between bacteriostatic and bactericidal effects. Recently, this method was successfully applied to blood culture pellets to determine the antibiotic susceptibility against agents of bloodstream infection [178]. AFM-nanomotion detection (NMD) has also been applied for AFST, where the effect of a low (10 µg/mL) and high (40 µg/mL) caspofungin concentration on C. albicans was evaluated [179].…”

Section: Nanomotion Analysis For Evaluating Antifungal Suscessibilitymentioning

confidence: 99%

Micro- and Nanoscale Approaches in Antifungal Drug Discovery

Willaert

2018

Fermentation

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Clinical needs for novel antifungal agents have increased due to the increase of people with a compromised immune system, the appearance of resistant fungi, and infections by unusual yeasts. The search for new molecular targets for antifungals has generated considerable research, especially using modern omics methods (genomics, genome-wide collections of mutants, and proteomics) and bioinformatics approaches. Recently, micro-and nanoscale approaches have been introduced in antifungal drug discovery. Microfluidic platforms have been developed, since they have a number of advantages compared to traditional multiwell-plate screening, such as low reagent consumption, the manipulation of a large number of cells simultaneously and independently, and ease of integrating numerous analytical standard operations and large-scale integration. Automated high-throughput antifungal drug screening is achievable by massive parallel processing. Various microfluidic antimicrobial susceptibility testing (AST) methods have been developed, since they can provide the result in a short time-frame, which is necessary for personalized medicine in the clinic. New nanosensors, based on detecting the nanomotions of cells, have been developed to further decrease the time to test antifungal susceptibility to a few minutes. Finally, nanoparticles (especially, silver nanoparticles) that demonstrated antifungal activity are reviewed.Fermentation 2018, 4, 43 2 of 23 antifungal classes have been reported since 2006 [7]. Current antifungal drugs show some limitations: Amphothericin B (a polyene antibiotic) displays a considerable toxicity and undesirable side effects [8,9], issues with pharmacokinetic properties (such as a short half-life of echinocandins) and activity spectrum, a small number of targets [10,11], and they can interact with other drugs, such as chemotherapy agents and immunosuppressants [12,13]. The last approved antifungal (i.e., anidulafungin) by the European Medicines Agency and the Food and Drug Administration (FDA) dates back to 2006 [14]. There is an urgent need for safer and more effective antifungal drugs. Multiple types of antifungal compounds are in clinical development and these new agents have been recently reviewed [15][16][17].Over the last 20 years, several approaches to antifungal discovery have been explored. The traditional approach seeks, first, to identify active compounds from large compound libraries using a panel of fungal pathogens in standardised assays when possible. In the genetic, genomic, or bioinformatics approach, the objective is, initially, to identify broadly represented targets in fungal pathogens and non-pathogens [18]. In this "target-centric" genomic approach, up-front genetic, bioinformatics, and biochemical target prioritisation is performed and, subsequently, an in vitro-based screening of individual targets is achieved. However, an exceedingly high rate of failure has been observed when applying this approach [19]. Additionally, not all bioactive compounds act through a target-specific mechan...

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Nanomechanical sensor applied to blood culture pellets: a fast approach to determine the antibiotic susceptibility against agents of bloodstream infections

Abstract: By combining the nanomotion sensor with the rapid preparation method of blood culture pellets, we obtained an innovative, rapid and relatively accurate method for antibiotic susceptibility test directly from positive blood culture bottles, without the need for bacterial subculture.

Cited by 57 publications

References 23 publications

Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow‐Growing Bacteria

Nanomotion Detection Method for Testing Antibiotic Resistance and Susceptibility of Slow‐Growing Bacteria

Cantilever Sensors for Rapid Optical Antimicrobial Sensitivity Testing

Micro- and Nanoscale Approaches in Antifungal Drug Discovery

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