Waterborne Elizabethkingia meningoseptica in adult critical care

Elizabethkingia meningoseptica is an infrequent colonizer of the respiratory tract; its pathogenicity is uncertain. In the context of a 22-month outbreak of E. meningoseptica acquisition affecting 30 patients in a London, UK, critical care unit (3% attack rate) we derived a measure of attributable morbidity and determined whether E. meningoseptica is an emerging nosocomial pathogen. We found monomicrobial E. meningoseptica acquisition (n = 13) to have an attributable morbidity rate of 54% (systemic inflammatory response syndrome >2, rising C-reactive protein, new radiographic changes), suggesting that E. meningoseptica is a pathogen. Epidemiologic and molecular evidence showed acquisition was water-source–associated in critical care but identified numerous other E. meningoseptica strains, indicating more widespread distribution than previously considered. Analysis of changes in gram-negative speciation rates across a wider London hospital network suggests this outbreak, and possibly other recently reported outbreaks, might reflect improved diagnostics and that E. meningoseptica thus is a pseudo-emerging pathogen

Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace

Closed-loop control for precision antimicrobial delivery: an In silico proof-of-concept

IEEE Objective: Inappropriate dosing of patients with antibiotics is a driver of antimicrobial resistance, toxicity, and poor outcomes of therapy. In this paper, we investigate, in silico, the hypothesis that the use of a closed-loop control system could improve the attainment of pharmacokinetic-pharmacodynamic targets for antimicrobial therapy, where wide variations in target attainment have been reported. This includes patients in critical care, patients with renal disease and patients with obesity

An insurance value modeling approach that captures the wider value of a novel antimicrobial to health systems, patients, and the population.

Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than localized (ward closure) scenarios, across perspectives. Components of this insurance value match previously published estimates of operational costs and mortality impacts. Conclusions: Insurance value of novel antimicrobials can be systematically modeled and substantially augments their traditional health economic value in normal circumstances. These approaches are generalizable to similar health interventions and form a framework for health systems and governments to capture broader value in health technology assessments, improve healthcare access, and increase resilience by planning for adverse scenarios

Obtaining antibiotics online from within the UK: a cross-sectional study

BACKGROUND: Improved antibiotic stewardship (AS) and reduced prescribing in primary care, with a parallel increase in personal internet use, could lead citizens to obtain antibiotics from alternative sources online. OBJECTIVES: A cross-sectional analysis was performed to: (i) determine the quality and legality of online pharmacies selling antibiotics to the UK public; (ii) describe processes for obtaining antibiotics online from within the UK; and (iii) identify resulting AS and patient safety issues. METHODS: Searches were conducted for 'buy antibiotics online' using Google and Yahoo. For each search engine, data from the first 10 web sites with unique URL addresses were reviewed. Analysis was conducted on evidence of appropriate pharmacy registration, prescription requirement, whether antibiotic choice was 'prescriber-driven' or 'consumer-driven', and whether specific information was required (allergies, comorbidities, pregnancy) or given (adverse effects) prior to purchase. RESULTS: Twenty unique URL addresses were analysed in detail. Online pharmacies evidencing their location in the UK ( n  = 5; 25%) required a prescription before antibiotic purchase, and were appropriately registered. Online pharmacies unclear about the location they were operating from ( n  = 10; 50%) had variable prescription requirements, and no evidence of appropriate registration. Nine (45%) online pharmacies did not require a prescription prior to purchase. For 16 (80%) online pharmacies, decisions were initially consumer-driven for antibiotic choice, dose and quantity. CONCLUSIONS: Wide variation exists among online pharmacies in relation to antibiotic practices, highlighting considerable patient safety and AS issues. Improved education, legislation, regulation and new best practice stewardship guidelines are urgently needed for online antibiotic suppliers

Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study

BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None

Cardiometabolic traits, sepsis and severe covid-19:a Mendelian randomization investigation

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