This pragmatic prospective implementation trial uses a rapid genotyping platform for the m.1555A>G variant to assess whether this technology could be implemented to avoid aminoglycoside-induced ototoxicity without disrupting normal clinical practice on neonatal intensive care units.

IntroductionIn conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss.Methods and analysisThe genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice.Ethics and disseminationApproval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study.Trial registration numberISRCTN13704894.Protocol versionV 1.3.

Background: Regular SARS-CoV-2 testing of healthcare workers (HCWs) has been proposed to prevent healthcare facilities becoming persistent reservoirs of infectivity. Using monoplex testing, widespread screening would be prohibitively expensive, and throughput may not meet demand. We propose a non-adaptive combinatorial (NAC) group-testing strategy to increase throughput and facilitate rapid turnaround via a single round of testing. Methods: NAC matrices were constructed for sample sizes of 700, 350 and 250 with replicates of 2, 4 and 5, respectively. Matrix performance was tested by simulation under different SARS-CoV-2 prevalence scenarios of 0.1-10%, with each simulation ran for 10,000 iterations. Outcomes included the proportions of re-tests required and the proportion of true negatives identified. NAC matrices were compared to Dorfman Sequential (DS) approaches. A web application (www.samplepooling.com) was designed to decode results. Findings: NAC matrices performed well at low prevalence levels with an average number of 585 tests saved per assay in the n=700 matrix at a 1% prevalence. As prevalence increased, matrix performance deteriorated with n=250 most tolerant. In simulations of low to medium (0.1%-3%) prevalence levels all NAC matrices were superior, as measured by fewer repeated tests required, to the DS approaches. At very high prevalence levels (10%) the DS matrix was marginally superior, however both group testing approaches performed poorly at high prevalence levels. Interpretation: This testing strategy maximises the proportion of samples resolved after a single round of testing, allowing prompt return of results to staff members. Using the methodology described here, laboratories can adapt their testing scheme based on required throughput and the current population prevalence, facilitating a data-driven testing strategy.

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