Accurate and rapid antibiotic susceptibility testing using a machine learning-assisted nanomotion technology platform.

Antimicrobial resistance (AMR) is a major public health threat, reducing treatment options for infected patients. AMR is promoted by a lack of access to rapid antibiotic susceptibility tests (ASTs). Accelerated ASTs can identify effective antibiotics for treatment in a timely and informed manner. We describe a rapid growth-independent phenotypic AST that uses a nanomotion technology platform to measure bacterial vibrations. Machine learning techniques are applied to analyze a large dataset encompassing 2762 individual nanomotion recordings from 1180 spiked positive blood culture samples covering 364 Escherichia coli and Klebsiella pneumoniae isolates exposed to cephalosporins and fluoroquinolones. The training performances of the different classification models achieve between 90.5 and 100% accuracy. Independent testing of the AST on 223 strains, including in clinical setting, correctly predict susceptibility and resistance with accuracies between 89.5% and 98.9%. The study shows the potential of this nanomotion platform for future bacterial phenotype delineation

Effectiveness of 2-year application of schoolbased chlorhexidine varnish, sodium fluoride gel, and dental health education programs in high-risk adolescents

PubMed ID: 18560640Objective: To compare the caries preventive effects of 2-year application of school-based chlorhexidine varnish, sodium fluoride gel, and dental health education programs among a high-risk group of 11- to 13-year-olds with low caries activity. Method and Materials: A total of 149 subjects who had previous caries experience in the primary dentition and Streptococcus mutans levels higher than 105 at baseline with 0 DMFS index were selected for this randomized clinical trial. Subjects were allocated to one of 3 groups for treatment with chlorhexidine varnish (n = 50), sodium fluoride gel (n = 50), or a dental health education program (n = 49), which were repeated throughout the 2-year study. The outcomes examined at the end of the study were the caries increment (DMFS index), dental plaque scores, and salivary S mutans counts. Results: The subjects in the education group showed a significant increase in the salivary levels of S mutans in comparison with the other groups (P = .004), but there was no significant difference among the groups in the caries increment after 2 years, with mean DMFS ± SD as 0.95 ± 1.33, 0.88 ± 1.47, and 1.05 ± 2.01 in the chlorhexidine varnish, sodium fluoride gel, and education groups, respectively. There were also no significant differences in the pre- and posttreatment plaque scores between the groups. Conclusion: Although all 3 preventive programs in this high-caries-risk group of children with low caries activity resulted in similar plaque and caries values after 2 years, longer follow-up studies are needed to clarify the effect of reduction in S mutans growth by chemotherapeutic agents in caries inciden. © 2008 by Quintessence Publishing Co Inc

Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation

Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes. We therefore investigated the core-ligand structure of two clinically relevant iron-carbohydrate complexes, iron sucrose (IS) and ferric carboxymaltose (FCM), and their interactions with two structurally different human plasma proteins, human serum albumin (HSA) and fibrinogen, using a combination of cryo-scanning transmission electron microscopy (cryo-STEM), x-ray diffraction (XRD), small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS). Using this orthogonal approach, we defined the nano-structure, individual building blocks and surface morphology for IS and FCM. Importantly, we revealed significant differences in the surface morphology of the iron-carbohydrate complexes. FCM shows a localised carbohydrate shell around its core, in contrast to IS, which is characterised by a diffuse and dynamic layer of carbohydrate ligand surrounding its core. We hypothesised that such differences in carbohydrate morphology determine the interaction between iron-carbohydrate complexes and proteins and therefore investigated the NPs in the presence of HSA and fibrinogen. Intriguingly, IS showed significant interaction with HSA and fibrinogen, forming NP-protein clusters, while FCM only showed significant interaction with fibrinogen. We postulate that these differences could influence bio-response of the two formulations and their clinical outcome. In conclusion, our study provides orthogonal characterisation of two clinically relevant iron-carbohydrate complexes and first hints at their interaction behaviour with proteins in the human bloodstream, setting a prerequisite towards complete understanding of the correlation between physicochemical properties and clinical outcome.ISSN:0168-3659ISSN:1873-499