scholarly journals Prediction of cephalosporin and carbapenem susceptibility in multi-drug resistant Gram-negative bacteria using liquid chromatography-tandem mass spectrometry

2017 ◽  
Author(s):  
Yuiko Takebayashi ◽  
Wan Ahmad Kamil Wan Nur Ismah ◽  
Jacqueline Findlay ◽  
Kate J. Heesom ◽  
Jay Zhang ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Susceptibility Testing ◽  
Bacterial Species ◽  
Clinical Decision ◽  
Drug Susceptibility ◽  
Clinical Samples ◽  
Correct Prediction ◽  
Antibacterial Drug ◽  
Liquid Chromatography Tandem Mass

ABSTRACTIn vitro antibacterial susceptibility testing informs clinical decision making concerning antibacterial therapeutics. Predicting, in a timely manner, which bacterial infection will respond to treatment by a given antibacterial drug reduces morbidity, mortality, and healthcare costs. It also allows prudent antibacterial use, because clinicians can focus on the least broad-spectrum agent suitable for each patient. Existing susceptibly testing methodologies rely on growth of bacteria in the presence of an antibacterial drug. There is significant interest in the possibility of predicting antibacterial drug susceptibility directly though the analysis of bacterial DNA or protein, because this may lead to more rapid susceptibility testing directly from clinical samples. Here we report a robust and tractable methodology that allows measurement of the abundance of key proteins responsible for antibacterial drug resistance within samples of 1 µg of total bacterial protein. The method allowed correct prediction of β-lactam susceptibility in clinical isolates from four key bacterial species and added considerable value over and above the information generated by whole genome sequencing, allowing for gene expression, not just gene presence to be considered, which is key when considering the complex interplays of multiple mechanisms of resistance.

scholarly journals Rapid pathogen-specific phenotypic antibiotic susceptibility testing using digital LAMP quantification in clinical samples

2017 ◽  
Vol 9 (410) ◽  
pp. eaal3693 ◽  
Author(s):  
Nathan G. Schoepp ◽  
Travis S. Schlappi ◽  
Matthew S. Curtis ◽  
Slava S. Butkovich ◽  
Shelley Miller ◽  
...  
Keyword(s):  
Antibiotic Susceptibility ◽  
Clinical Decision Making ◽  
Susceptibility Testing ◽  
Area Under The Curve ◽  
Clinical Decision ◽  
Urine Samples ◽  
Clinical Samples ◽  
E Coli ◽  
Digital Polymerase Chain Reaction ◽  
Time Loop

Rapid antimicrobial susceptibility testing (AST) is urgently needed for informing treatment decisions and preventing the spread of antimicrobial resistance resulting from the misuse and overuse of antibiotics. To date, no phenotypic AST exists that can be performed within a single patient visit (30 min) directly from clinical samples. We show that AST results can be obtained by using digital nucleic acid quantification to measure the phenotypic response ofEscherichia colipresent within clinical urine samples exposed to an antibiotic for 15 min. We performed this rapid AST using our ultrafast (~7 min) digital real-time loop-mediated isothermal amplification (dLAMP) assay [area under the curve (AUC), 0.96] and compared the results to a commercial (~2 hours) digital polymerase chain reaction assay (AUC, 0.98). The rapid dLAMP assay can be used with SlipChip microfluidic devices to determine the phenotypic antibiotic susceptibility ofE. colidirectly from clinical urine samples in less than 30 min. With further development for additional pathogens, antibiotics, and sample types, rapid digital AST (dAST) could enable rapid clinical decision-making, improve management of infectious diseases, and facilitate antimicrobial stewardship.

scholarly journals Establishment and Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma

2021 ◽  
Author(s):  
Yanbo DONG ◽  
Jian WANG ◽  
Wei JI ◽  
Mengzhu ZHENG ◽  
Peng WANG ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Drug Testing ◽  
Clinical Decision Making ◽  
Cell Model ◽  
Clinical Decision ◽  
Culture Technique ◽  
Hypopharyngeal Carcinoma ◽  
Molecular Characteristics ◽  
Drug Responses

Abstract Purpose Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to their anatomic location and highly variable therapeutic responses. We aim to establish a new in vitro model for LHSCC based on conditional reprogramming (CR), a novel cell-culture technique, and investigate its potential value on personalized cancer therapies. Methods Primary LHSCC cells were isolated from tumor specimens and cultured under CR conditions. The characteristics and malignant potential of cells were evaluated by histological staining, whole-exome sequencing and heterotransplantation. The responses of CR tumor cells to anticancer drugs and radiotherapy were tested using cell proliferation assay. CR cells could form xenografts and organoids, which were used for drug testing respectively. Clinical responses for certain patients were also compared with in vitro responses. Results A panel of 28 human LHSCC CR cells were established from 50 tumor tissues. They retain tumorigenic potential upon xenotransplantation and recapitulate molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells can be transformed to xenograft and organoid, shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Conclusions The patient-derived CR cell model could promisingly be utilized in clinical decision-making and assist in the selection of personalized therapies for LHSCC.

scholarly journals Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing

2020 ◽  
Vol 6 (1) ◽  
pp. 12 ◽  
Author(s):  
Mireille H. van der Torre ◽  
Lilyann Novak-Frazer ◽  
Riina Rautemaa-Richardson
Keyword(s):  
Dna Sequencing ◽  
Susceptibility Testing ◽  
Simultaneous Detection ◽  
Drug Susceptibility ◽  
Turnaround Time ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Diagnostic Methods ◽  
Resistance Testing ◽  
Clinical Samples

Guidelines on the diagnosis and management of Aspergillus disease recommend a multi-test approach including CT scans, culture, fungal biomarker tests, microscopy and fungal PCR. The first-line treatment of confirmed invasive aspergillosis (IA) consists of drugs in the azole family; however, the emergence of azole-resistant isolates has negatively impacted the management of IA. Failure to detect azole-resistance dramatically increases the mortality rates of azole-treated patients. Despite drug susceptibility tests not being routinely performed currently, we suggest including resistance testing whilst diagnosing Aspergillus disease. Multiple tools, including DNA sequencing, are available to screen for drug-resistant Aspergillus in clinical samples. This is particularly beneficial as a large proportion of IA samples are culture negative, consequently impeding susceptibility testing through conventional methods. Pyrosequencing is a promising in-house DNA sequencing method that can rapidly screen for genetic hotspots associated with antifungal resistance. Pyrosequencing outperforms other susceptibility testing methods due to its fast turnaround time, accurate detection of polymorphisms within critical genes, including simultaneous detection of wild type and mutated sequences, and—most importantly—it is not limited to specific genes nor fungal species. Here we review current diagnostic methods and highlight the potential of pyrosequencing to aid in a diagnosis complete with a resistance profile to improve clinical outcomes.

scholarly journals Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review

CJEM ◽  
2010 ◽  
Vol 12 (05) ◽  
pp. 435-442 ◽  
Author(s):  
Brian E. Grunau ◽  
Matthew O. Wiens ◽  
Jeffrey R. Brubacher
Keyword(s):  
Systematic Review ◽  
Clinical Decision Making ◽  
Case Reports ◽  
Data Extraction ◽  
Patient Characteristics ◽  
Clinical Decision ◽  
Poison Control ◽  
Published Data ◽  
Published Evidence

ABSTRACTObjective:The use of dantrolene in the treatment of hyperpyrexia related to MDMA (3,4-methylenedioxymethamphetamine) is controversial, with little data available to guide clinical decision-making. Although the treatment is recommended by several poison control centres, published data are primarily in the form of case reports and animal and in vitro experiments. We conducted a systematic review to investigate the published evidence regarding the safety and benefits of dantrolene for MDMA-related hyperpyrexia in humans.Data sources:A systematic search of Embase and MEDLINE was conducted from the earliest possible date to November 2008.Study selection:All human trials and case reports of MDMA-related hyperpyrexia were considered.Data extraction:Data were abstracted systematically and characteristics including use of dantrolene, adverse reactions attributed to dantrolene, peak temperature, complications from MDMA-related hyperpyrexia and survival were recorded.Data synthesis:Our search yielded 668 articles of which 53, reporting 71 cases of MDMA-induced hyperpyrexia, met our inclusion criteria. No clinical trials, randomized controlled trials, observational studies or meta-analyses were identified. Dantrolene was used in 26 cases. Patient characteristics were similar in the dantrolene and no dantrolene groups. The proportion of survivors was higher in the dantrolene group (21/26) than in the no dantrolene group (25/45). This difference was especially pronounced in those with extreme (≥ 42°C) and severe (≥ 40°C) fever, with a survival rate of 8 of 13 and 10 of 10, respectively, in the dantrolene group compared with 0 of 4 and 15 of 27 in the no dantrolene group. There were no reports of adverse events attributable to dantrolene with the exception of a possible association with an episode of transient hypoglycemia.Conclusion:Our systematic review suggests that dantrolene is safe for patients with MDMA-related hyperpyrexia. Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia, although this conclusion must be interpreted with caution given the risk of reporting or publication bias.

THE VALUE OF IN VITRO DIAGNOSTIC TESTING IN THE PROVISION OF MEDICAL CARE TO ELDERLY PATIENTS WITH CARDIOVASCULAR DISEASES

2020 ◽  
Vol 65 (3) ◽  
pp. 191-196
Author(s):  
A. S. Pushkin ◽  
O. V. Lyang ◽  
T. A. Ahmedov ◽  
S. A. Rukavishnikova
Keyword(s):  
Decision Making ◽  
Medical Care ◽  
Laboratory Tests ◽  
Clinical Decision Making ◽  
Diagnostic Testing ◽  
Clinical Decision ◽  
Initial Examination ◽  
Attending Physicians ◽  
The Impact

In vitro diagnostics are used at all stages of patient care. The aim of this study was to assess the impact of laboratory examination on clinical decision-making in providing medical care to patients with a cardiovascular profile. We also took into account the level of financing for the laboratory industry in the Russian Federation. We divided our study on three sequential steps: literature review, survey of clinicians and test-survey of clinicians. The share of costs for the laboratory tests in 2017 amounted to about 8% of the total funding for Russian health care. About 80% (70; 90) of the visits of the attending physicians are associated with the appointment of laboratory tests. Among patients who were prescribed any laboratory test - in 62.1% (95% CI 16.9-24.9) cases, the results of these tests influenced clinical decision making related to the initiation, modification or termination of any treatment. All visits of clinicians were divided by purpose: tests were prescribed in almost 100% (90; 100) cases during the initial examination, in 40% (20; 60) cases during repeated visits, and in 40% (15; 40) cases when patients were examined before discharge. In more than half of cases (57,4%; n=31), doctors correctly assumed about the about the share of financing of the laboratory industry. The majority of respondents considered the amount of expenses adequate and recommended to maintain the current level in the future. According to attending physicians, new laboratory markers should demonstrate additional information about clinical relevance to improve patient outcomes. Thus, in current economic realities, future laboratory tests should be financially maximally available and at the same time be clinically highly effective auxiliary instruments. It creates new challenges in finding laboratory biomarkers and putting them into clinical practice.

scholarly journals A New Device to Automate the Monitoring of Critical Patients’ Urine Output

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Otero ◽  
Andrey Apalkov ◽  
Roemi Fernández ◽  
Manuel Armada
Keyword(s):  
Patient Outcomes ◽  
Urine Output ◽  
Clinical Decision Making ◽  
Capacitive Sensor ◽  
Clinical Decision ◽  
In Vitro Tests ◽  
Therapeutic Goals ◽  
New Device ◽  
Improve Patient

Urine output (UO) is usually measured manually each hour in acutely ill patients. This task consumes a substantial amount of time. Furthermore, in the literature there is evidence that more frequent (minute-by-minute) UO measurement could impact clinical decision making and improve patient outcomes. However, it is not feasible to manually take minute-by-minute UO measurements. A device capable of automatically monitoring UO could save precious time of the healthcare staff and improve patient outcomes through a more precise and continuous monitoring of this parameter. This paper presents a device capable of automatically monitoring UO. It provides minute by minute measures and it can generate alarms that warn of deviations from therapeutic goals. It uses a capacitive sensor for the measurement of the UO collected within a rigid container. When the container is full, it automatically empties without requiring any internal or external power supply or any intervention by the nursing staff. In vitro tests have been conducted to verify the proper operation and accuracy in the measures of the device. These tests confirm the viability of the device to automate the monitoring of UO.

Integrated Diagnostics for Rapid Quantitation of Biomarkers in Human Fluids

2010 ◽  
Author(s):  
Chenlu Hou ◽  
Kelly Karns ◽  
Amy E. Herr
Keyword(s):  
Differential Diagnosis ◽  
Clinical Decision Making ◽  
Clinical Medicine ◽  
Clinical Decision ◽  
Specific Protein ◽  
Clinical Diagnostics ◽  
Clinical Samples ◽  
Field Hospital ◽  
Multiple Biomarkers ◽  
Microfluidic Assays

A fast, accurate differential diagnosis is a tremendous challenge in clinical medicine. For example, in emergency settings differential diagnosis of infection from inflammation is needed, as a timely and actionable diagnosis is critical. Consequently, diagnostics capable of measuring multiple biomarkers would support clinical decision-making related to diagnosis, containment, and treatment. Microfluidic assays are exceptionally well-suited for near-patient clinical diagnostics (i.e., ambulance, emergency room, field hospital). We present spectrally multiplexed homogeneous electrophoretic immunoassays for specific protein disease biomarkers. Biomarkers are resolved quickly (< 60 s), in ultra-short separation lengths (< 1 mm), and at clinically relevant concentrations (nM). On-going work will be presented and centers on endogenous protein measurements in clinical samples in support of near-patient assessment.

scholarly journals Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas

2020 ◽  
Vol 7 (1) ◽  
pp. e000505
Author(s):  
Emoke Papp ◽  
Anita Steib ◽  
Elhusseiny MM Abdelwahab ◽  
Judit Meggyes-Rapp ◽  
Laszlo Jakab ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Therapy Response ◽  
Clinical Decision ◽  
Response To Therapy ◽  
Solid Tumours ◽  
Chemosensitivity Test ◽  
Pleural Effusions ◽  
In Vitro Chemosensitivity ◽  
Lung Adenocarcinomas

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.

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