scholarly journals The Genotype to Phenotype Dilemma: How Should Laboratories Approach Discordant Susceptibility Results?

Author(s):  
Rebecca Yee ◽  
Jennifer Dien Bard ◽  
Patricia J Simner

Abstract: Traditional culture-based methods for identification and antimicrobial susceptibility testing (AST) of bacteria on average takes 2-3 days. Syndromic molecular diagnostic panels have revolutionized clinical microbiology laboratories as they can simultaneously identify an organism and detect some of the most significant antimicrobial resistance (AMR) genes directly from positive blood culture broth or from various specimen types (e.g., whole blood, cerebrospinal fluid, respiratory specimens). The presence or absence of an AMR marker associated with a particular organism can be used to predict the phenotypic AST results to more rapidly guide therapy. Numerous studies have shown that genotypic susceptibility predictions by syndromic panels can improve patient outcomes. However, an important limitation of AMR marker detection to predict phenotype is the potential discrepancies that may arise upon performing phenotypic AST of the recovered organism in culture. The focus of this minireview is to address how clinical laboratories should interpret rapid molecular results from commercial platforms in relation to phenotypic AST. Stepwise approaches and solutions are provided to resolve discordant results between genotypic and phenotypic susceptibility results.

2020 ◽  
Vol 75 (12) ◽  
pp. 3501-3509
Author(s):  
Lilyann Novak-Frazer ◽  
Samuel P Anees-Hill ◽  
Darin Hassan ◽  
Rikesh Masania ◽  
Caroline B Moore ◽  
...  

Abstract Background Infections caused by triazole drug-resistant Aspergillus fumigatus are an increasing problem. The sensitivity of standard culture is poor, abrogating susceptibility testing. Early detection of resistance can improve patient outcomes, yet tools for this purpose are limited. Objectives To develop and validate a pyrosequencing technique to detect resistance-conferring cyp51A polymorphisms from clinical respiratory specimens and A. fumigatus isolates. Methods Method validation was performed by Sanger sequencing and pyrosequencing of 50 A. fumigatus isolates with a spectrum of triazole susceptibility patterns. Then, 326 Aspergillus quantitative PCR (qPCR)-positive respiratory samples collected over a 27 month period (January 2017–March 2019) from 160 patients at the UK National Aspergillosis Centre were assessed by cyp51A pyrosequencing. The Sanger sequencing and pyrosequencing results were compared with those from high-volume culture and standard susceptibility testing. Results The cyp51A genotypes of the 50 isolates analysed by pyrosequencing and Sanger sequencing matched. Of the 326 Aspergillus qPCR-positive respiratory specimens, 71.2% were reported with no A. fumigatus growth. Of these, 56.9% (132/232) demonstrated a WT cyp51A genotype and 31.5% (73/232) a resistant genotype by pyrosequencing. Pyrosequencing identified the environmental TR34/L98H mutation in 18.7% (61/326) of the samples in contrast to 6.4% (21/326) pan-azole resistance detected by culture. Importantly, pyrosequencing detected resistance earlier than culture in 23.3% of specimens. Conclusions The pyrosequencing assay described could detect a wide range of cyp51A polymorphisms associated with triazole resistance, including those not identified by commercial assays. This method allowed prompt recognition of resistance and the selection of appropriate antifungal treatment when culture was negative.


Author(s):  
Sheri Palejwala ◽  
Jonnae Barry ◽  
Crystal Rodriguez ◽  
Chandni Parikh ◽  
Stephen Goldstein ◽  
...  

2012 ◽  
Vol 9 (2) ◽  
pp. 96-98
Author(s):  
Brian A Bruckner ◽  
Matthias Loebe

Patients undergoing re-operative cardiac surgical procedures present a great challenge with regard to obtaining hemostasis in the surgical field. Adhesions are ever-present and these patients are often on oral anti-coagulants and platelet inhibitors. As part of a well-planned surgical intervention, a systematic approach to hemostasis should be employed to decrease blood transfusion requirement and improve patient outcomes. Topical hemostatic agents can be a great help to the surgeon in achieving surgical field hemostasis and are increasingly being employed. Our approach, to these difficult patients, includes the systematic and planned use of AristaAH, which is a novel hemostatic agent whose use has proven safe and efficacious in our patient population.


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e041743
Author(s):  
Christina Østervang ◽  
Annmarie Touborg Lassen ◽  
Charlotte Myhre Jensen ◽  
Elisabeth Coyne ◽  
Karin Brochstedt Dieperink

IntroductionThe development of acute symptoms or changes in diseases led to feelings of fear and vulnerability and the need for health professional support. Therefore, the care provided in the acute medical and surgical areas of the emergency department (ED) is highly important as it influences the confidence of patients and families in managing everyday life after discharge. There is an increase in short-episode (<24 hours) hospital admissions, related to demographic changes and a focus on outpatient care. Clear discharge information and inclusion in treatment decisions increase the patient’s and family’s ability to understand and manage health needs after discharge, reduces the risk of readmission. This study aims to identify the needs for ED care and develop a solution to improve outcomes of patients discharged within 24 hours of admission.Methods and analysisThe study comprises the three phases of a participatory design (PD). Phase 1 aims to understand and identify patient and family needs when discharged within 24 hours of admission. A qualitative observational study will be conducted in two different EDs, followed by 20 joint interviews with patients and their families. Four focus group interviews with healthcare professionals will provide understanding of the short pathways. Findings from phase 1 will inform phase 2, which aims to develop a solution to improve patient outcomes. Three workshops gathering relevant stakeholders are arranged in the design plus development of a solution with specific outcomes. The solution will be implemented and tested in phase 3. Here we report the study protocol of phase 1 and 2.Ethics and disseminationThe study is registered with the Danish Data Protection Agency (19/22672). Approval of the project has been granted by the Regional Committees on Health Research Ethics for Southern Denmark (S-20192000–111). Findings will be published in suitable international journals and disseminated through conferences.


2021 ◽  
Vol 50 (Supplement_1) ◽  
pp. i12-i42
Author(s):  
C Abbott ◽  
K Bishop ◽  
F Hill ◽  
C Finlow ◽  
R Maraj

Abstract Introduction In September 2017 our frailty service was started within our medium sized DGH in North Wales. Working with our management team we secured a significant clinical resource including: We describe how resources, setting and staffing develop over a 2 year period in order to create a service which meets the needs of the local population. Method The service has been in a constant state of development since it has been in operation, utilising a PDSA model with regular meetings of clinical and managerial staff to analyse performance. Results With each new PDSA cycle the amount of patients reviewed has increased. With the move to AMU we increased the monthly number of patients reviewed from 29 to 172 patients reviewed, 97 of which were discharged directly from the unit. Conclusion Using QI methodology our Frailty Service has improved dramatically since its inception. We will continue to analyse how we work to improve patient outcomes and cost effectiveness.


2021 ◽  
Vol 22 (5) ◽  
pp. 481-508
Author(s):  
Robert P. Carlyon ◽  
Tobias Goehring

AbstractCochlear implants (CIs) are the world’s most successful sensory prosthesis and have been the subject of intense research and development in recent decades. We critically review the progress in CI research, and its success in improving patient outcomes, from the turn of the century to the present day. The review focuses on the processing, stimulation, and audiological methods that have been used to try to improve speech perception by human CI listeners, and on fundamental new insights in the response of the auditory system to electrical stimulation. The introduction of directional microphones and of new noise reduction and pre-processing algorithms has produced robust and sometimes substantial improvements. Novel speech-processing algorithms, the use of current-focusing methods, and individualised (patient-by-patient) deactivation of subsets of electrodes have produced more modest improvements. We argue that incremental advances have and will continue to be made, that collectively these may substantially improve patient outcomes, but that the modest size of each individual advance will require greater attention to experimental design and power. We also briefly discuss the potential and limitations of promising technologies that are currently being developed in animal models, and suggest strategies for researchers to collectively maximise the potential of CIs to improve hearing in a wide range of listening situations.


Neurosurgery ◽  
2021 ◽  
Author(s):  
Kelly M Poth ◽  
Pavlos Texakalidis ◽  
Nicholas M Boulis

Abstract The field of chemogenetics has rapidly expanded over the last decade, and engineered receptors are currently utilized in the lab to better understand molecular interactions in the nervous system. We propose that chemogenetic receptors can be used for far more than investigational purposes. The potential benefit of adding chemogenetic neuromodulation to the current neurosurgical toolkit is substantial. There are several conditions currently treated surgically, electrically, and pharmacologically in clinic, and this review highlights how chemogenetic neuromodulation could improve patient outcomes over current neurosurgical techniques. We aim to emphasize the need to take these techniques from bench to bedside.


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