MICROBIAL TECHNOLOGY


based on RDT results enhance the overall efficacy of the antimicrobial stewardship programme.


Defining rapid diagnostic tests When summarised in a general way as above, it can be seen that the use of RDTs in the diagnosis of infectious disease must be a ‘good thing’; however, the picture becomes a lot less clear when examined in any detail to try and look for high- quality evidence in support of a particular test or groups of tests and how they should be used.


For example, what is a rapid test anyway? There is in fact no agreed definition of what constitutes a rapid test. A rapid test is often understood as being any test that produces an actionable result in less time than that taken using a culture-based test. Others, however, tend to restrict use of the term to tests that are POC-based so the time taken to transport specimens to the laboratory and report results is removed from the equation, while yet others would consider the use of MALDI-TOF identification of bacteria that have been cultured, as a rapid test as it may reduce the time taken for identification and possibly AST determination by 24 hours. Take the case of neonatal sepsis.


Here, historically, the treatment approach has included early aggressive initiation of antibiotics because of the neonate’s relative immunosuppression. Because early signs of sepsis in the newborn are non-specific, diagnostic studies are often ordered and treatment initiated in neonates before the presence of sepsis has been proven or excluded. Many asymptomatic neonates now undergo evaluation and are exposed to antibiotics. This approach has been questioned in recent years as more evidence emerges of the deleterious impact of unnecessary antibiotic exposure, including interference with the establishment of breast feeding, alterations in gut microbiome, increased incidence of childhood obesity and


development of antimicrobial resistance, among others. Astonishingly, among very low birthweight infants who were initially treated with antibiotics but subsequently found to have negative cultures, there is actually an increased risk of mortality and stage 3 retinopathy of prematurity. In other words, in addition to the well- described general risks of overprescribing as mentioned above, there is the possibility of causing direct and immediate harm to the infant who did not have sepsis to begin with.


Role of inflammatory biomarkers There is often very little agreement on the performance even of tests like C-reactive protein (CRP) and procalcitonin (PCT), which have been in use for decades and are relatively cheap and easy to perform. At the BSMT meeting in May 2020, Professor Paul Dark, National Deputy Medical Director, NIHR Clinical Research Network, described the protocol for a multicentre randomised, controlled trial looking at the use of these two inflammatory biomarkers (CRP and PCT) in the management of hospitalised patients with suspected sepsis. While many ICUs use one or other of the tests, implementation has been highly variable and the evidence base underlying the implementation is often minimal or non- existent, just the belief that one or other of the tests is a ‘good test’. Many clinicians will vehemently support the use of one of these two tests while decrying the other based on their own experience or small trials. Indeed, it has been said that the only thing missing from the CRP test is the letter A. Professor Dark’s trial (biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis [ADAPT- Sepsis]) aims to finally provide the high-quality evidence on the usefulness of these two tests. The trial that Professor Dark described commenced in May 2017


and is due to finish recruitment in July 2024 – like many other trials, it has been held up by COVID-19. A total sample size of 2760 will be required to reliably detect a mean of one-day reduction in antibiotic duration. The trial will take up to six years, including follow-up, to produce a result.


Assessing the value of RDTs If it has taken decades to get to the stage where we will definitively be able to determine the usefulness of CRP and PCT tests, how then should we evaluate the plethora of new tests being introduced, some of which will be on display in the exhibition at the BSMT meeting in May? To throw some light on this confusing picture, we are therefore particularly lucky to welcome Dr Luke Moore, Consultant Infectious Diseases, Microbiology, & Virology, Chelsea & Westminster NHS Foundation Trust, to give the introductory keynote speech on how we assess and value rapid diagnostics. Dr Moore has been instrumental in setting up an expert working group from low-middle and high income countries to assess the value of RDTs in antimicrobial stewardship programmes and how they can be implemented in countries with vastly different resources. They have proposed the following global definition of RDTs for use in antimicrobial stewardship programmes: infectious disease RDTs include both microbial and host assays which can be conducted and actioned within a 24-hour period that can substantially support ASPs.


Sequencing revolution Two years ago at this meeting, Adela Alcolea-Medina, Clinical Scientist from Guy’s & St Thomas’ Hospital, London, described her work on the development of rapid sequencing methods for the detection of respiratory pathogens, aimed at producing actionable results within eight hours rather than 24 hours. In those two years the methods have been refined and are now capable of


Severn Biotech www.severnbiotech.com


reagents


Tel: +44 (0)1562 825286 Fax: +44 (0)1562 825284 E-mail: info@servernbiotech.com


Our reagents are made from the highest quality pure materials to exact standards. ISO 9001 : 2015 accredited. WWW.PATHOLOGYINPRACTICE.COM FEBRUARY 2024 15 molecular biology/lab


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56