Publications by authors named "Luke Moore"

97 Publications

Necrosis and amputation following the bite of the Bibron's stiletto snake () with a concise review of current literature.

Trop Doct 2021 Sep 7:494755211039638. Epub 2021 Sep 7.

Consultant Infectious Diseases, Microbiology and Virology, Chelsea and Westminster Hospital, London, UK.

are highly specialised snakes found across Southern Africa. Adapted for subterranean hunting of prey, snakes of the genus demonstrate a unique biting mechanism, with an ability to deliver venom via a single fang, protruded over an almost closed mouth in a side-to-side striking pattern. It is not possible to handle these snakes safely. can be mistaken for medically insignificant snakes and often occur in remote areas that may lead to delayed or reduced presentation to suitable care facilities. We here report a case of an envenomation in remote Southern Africa to the right ring finger from a single fang with significant complication. Medical, and subsequently, surgical management of a progression from discolouration at the bite site, to spreading oedema, blistering, local necrosis and secondary infection required amputation of the digit.
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http://dx.doi.org/10.1177/00494755211039638DOI Listing
September 2021

Ceftazidime-Avibactam for the Treatment of Serious Gram-Negative Infections with Limited Treatment Options: A Systematic Literature Review.

Infect Dis Ther 2021 Aug 11. Epub 2021 Aug 11.

Global Medical Affairs, Anti-infectives, Pfizer, Tadworth, Surrey, UK.

Introduction: A systematic literature review was undertaken to evaluate real-world use of ceftazidime-avibactam for infections due to aerobic Gram-negative organisms in adults with limited treatment options.

Methods: Literature searches retrieved peer-reviewed publications and abstracts from major international infectious disease congresses from January 2015 to February 2021. Results were screened using pre-defined criteria to limit the dataset to relevant publications (notable exclusions were paediatric data and outcomes data for bacteria intrinsically resistant to ceftazidime-avibactam). Data for included publications were subjected to qualitative synthesis.

Results: Seventy-three relevant publications (62 peer-reviewed articles; 10 abstracts) comprising 1926 patients treated with ceftazidime-avibactam (either alone or combined with other antimicrobials) and 1114 comparator/control patients were identified. All patients were hospitalised for serious illness and most had multiple comorbidities. The most common infections were pneumonia, bacteraemia, and skin/soft tissue, urinary tract, or abdominal infections; smaller numbers of patients with meningitis, febrile neutropenia, osteomyelitis, and cystic fibrosis were also included. Carbapenem-resistant or carbapenemase-producing Enterobacterales (CRE; n = 1718) and carbapenem-resistant, multidrug-resistant (MDR), and extensively drug-resistant Pseudomonas aeruginosa (n = 150) were the most common pathogens. Most publications reported positive outcomes for ceftazidime-avibactam treatment (clinical success rates ranged from 45 to 100% and reported 30-day mortality from 0 to 63%), which were statistically superior versus comparators in some studies. ceftazidime-avibactam resistance emergence occurred infrequently and mostly in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae strains.

Conclusion: This review provides qualitative evidence of successful use of ceftazidime-avibactam for the treatment of hospitalised patients with CRE and MDR P. aeruginosa infections with limited treatment options.
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http://dx.doi.org/10.1007/s40121-021-00507-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355581PMC
August 2021

Real-world evaluation of COVID-19 lateral flow device (LFD) mass-testing in healthcare workers at a London hospital; a prospective cohort analysis.

J Infect 2021 Aug 5. Epub 2021 Aug 5.

Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH, United Kingdom.

Objectives: Real-world evaluation of the performance of the Innova lateral flow immunoassay antigen device (LFD) for regular COVID-19 testing of hospital workers.

Methods: This prospective cohort analysis took place at a London NHS Trust. 5076 secondary care healthcare staff participated in LFD testing from 18 November 2020 to21 January 2021. Staff members submitted results and symptoms via an online portal twice weekly. Individuals with positive LFD results were invited for confirmatory SARS CoV-2 PCR testing. The positive predictive value (PPV) of the LFD was measured. Secondary outcome measures included time from LFD result to PCR test and staff symptom profiles.

Results: 284/5076 individuals reported a valid positive LFD result, and a paired PCR result was obtained in 259/284 (91.2%). 244 were PCR positive yielding a PPV of 94.21% (244/259, 95% CI 90.73% to 96.43%). 204/259 (78.8%) staff members had the PCR within 36 hours of the LFD test. Symptom profiles were confirmed for 132/244 staff members (54.1%) with positive PCR results (true positives) and 13/15 (86.6%) with negative PCR results (false positives). 91/132 true positives (68.9%) were symptomatic at the time of LFD testing: 65/91 (71.4%) had symptoms meeting the PHE case definition of COVID-19, whilst 26/91 (28.6%) had atypical symptoms. 18/41 (43.9%) staff members who were asymptomatic at the time of positive LFD developed symptoms in the subsequent four days. 9/13 (76.9%) false positives were asymptomatic, 1/13 (7.7%) had atypical symptoms and 3/13 (23.1%) had symptoms matching the PHE case definition.

Conclusions: The PPV of the Innova LFD is high when used amongst hospital staff during periods of high prevalence of COVID-19, yet we find frequent use by symptomatic staff rather than as a purely asymptomatic screening tool. LFD testing does allow earlier isolation of infected workers and facilitates detection of individuals whose symptoms do not qualify for PCR testing.
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http://dx.doi.org/10.1016/j.jinf.2021.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340567PMC
August 2021

Association between SARS-CoV-2 exposure and antibody status among healthcare workers in two London hospitals: a cross-sectional study.

Infect Prev Pract 2021 Sep 22;3(3):100157. Epub 2021 Jun 22.

London School of Hygiene and Tropical Medicine, Keppel Street, London, UK.

Background: Patient-facing (frontline) health-care workers (HCWs) are at high risk of repeated exposure to SARS-CoV-2.

Aim: We sought to determine the association between levels of frontline exposure and likelihood of SARS-CoV-2 seropositivity amongst HCW.

Methods: A cross-sectional study was undertaken using purposefully collected data from HCWs at two hospitals in London, United Kingdom (UK) over eight weeks in May-June 2020. Information on sociodemographic, clinical and occupational characteristics was collected using an anonymised questionnaire. Serology was performed using split SARS-CoV-2 IgM/IgG lateral flow immunoassays. Exposure risk was categorised into five pre-defined ordered grades. Multivariable logistic regression was used to examine the association between being frontline and SARS-CoV-2 seropositivity after controlling for other risks of infection.

Findings: 615 HCWs participated in the study. 250/615 (40.7%) were SARS-CoV-2 IgM and/or IgG positive. After controlling for other exposures, there was non-significant evidence of a modest association between being a frontline HCW (any level) and SARS-CoV-2 seropositivity compared to non-frontline status (OR 1.39, 95% CI 0.84-2.30, =0.200). There was 15% increase in the odds of SARS-CoV-2 seropositivity for each step along the frontline exposure gradient (OR 1.15, 95% CI 1.00-1.32, =0.043).

Conclusion: We found a high SARS-CoV-2 IgM/IgG seropositivity with modest evidence for a dose-response association between increasing levels of frontline exposure risk and seropositivity. Even in well-resourced hospital settings, appropriate use of personal protective equipment, in addition to other transmission-based precautions for inpatient care of SARS-CoV-2 patients could reduce the risk of hospital-acquired SARS-CoV-2 infection among frontline HCW.
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http://dx.doi.org/10.1016/j.infpip.2021.100157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217738PMC
September 2021

Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing.

BMC Infect Dis 2021 Jul 8;21(1):665. Epub 2021 Jul 8.

North West London Pathology, Imperial College Healthcare NHS Trust, Fulham Palace Road, London, W6 8RF, UK.

Background: As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients' samples.

Method: We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals' sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing.

Results: Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0-60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6-56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13-60 vs. pooled sputum MAR 25.3, SD 14.6, range 1-54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12-3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal.

Conclusion: We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population "bubble".
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http://dx.doi.org/10.1186/s12879-021-06316-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265726PMC
July 2021

Evaluation of a thrice weekly administration of teicoplanin in the outpatient setting: a retrospective observational multicentre study.

JAC Antimicrob Resist 2021 Mar 21;3(1):dlab012. Epub 2021 Feb 21.

Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK.

Introduction: The glycopeptide teicoplanin is commonly utilized to facilitate outpatient parenteral antimicrobial therapy (OPAT). Licensed for once daily maintenance dosing, teicoplanin's long half-life allows for less frequent dosing (e.g. thrice weekly) following successful loading. This service evaluation reviews the safety and effectiveness of a novel thrice weekly teicoplanin dosing regimen.

Methods: A retrospective, observational study was conducted at Chelsea and Westminster Hospital (March 2018 to July 2020), evaluating trough serum teicoplanin concentrations for patients receiving >5 days of teicoplanin in the OPAT setting. Teicoplanin dosing and administration (once daily versus thrice weekly), clinical outcomes and therapeutic levels were analysed for all patients. The project was registered with clinical governance locally.

Results: A total of 82 patients treated with teicoplanin in the OPAT service were included; 53/82 receiving thrice weekly and 29/82 receiving once daily dosing. Mean teicoplanin trough levels were similar in both groups (26.2 mg/L and 25.8 mg/L in once daily and thrice weekly groups, =0.8895). High clinical success rates were recorded in both groups (25/29 [86.2%] versus 50/53 [94.3%]). No correlation with clinical outcomes and initial teicoplanin serum levels was identified. Normal renal function (>90 mL/min) was associated with lower teicoplanin serum concentrations (mean [±SD] 21.4 mg/L [±10.1] versus 29.7 mg/L [±14], =0.0178) in the thrice weekly dosed group but not with the once daily dosed group (mean [±SD] 28.2 mg/L [±9.4] versus 23.7 mg/L [±9.9], =0.2201).

Conclusions: This study supports thrice weekly teicoplanin as a convenient and effective OPAT for administration in the OPAT setting. Therapeutic drug monitoring is advised to adjust for intra-patient variability.
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http://dx.doi.org/10.1093/jacamr/dlab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210249PMC
March 2021

Clinical outcomes of temocillin use for invasive Enterobacterales infections: a single-centre retrospective analysis.

JAC Antimicrob Resist 2021 Mar 14;3(1):dlab005. Epub 2021 Feb 14.

Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK.

Background: With increasing frequency of resistant Gram-negative bacteria, temocillin has potential utility in reducing carbapenem use. The 2020 EUCAST guideline changes temocillin breakpoints and reclassifies isolates with an MIC of 0.001-16 mg/L as 'susceptible, increased exposure' necessitating 6 g/day rather than the previous 4 g/day, associated with significant cost implications.

Objectives: We explore the clinical utility and treatment failure rate of temocillin at 4 g/day dosing.

Methods: All adult inpatient electronic prescriptions of temocillin (3 days or greater) from March 2016 to October 2019 were retrieved using a clinical decision support system (ICNET). Treatment success was defined as survival, no switch to broad-spectrum agent for the same indication and no subsequent recrudescence of infection, occurring within 30 days.

Results: Temocillin was used in 205 eligible patient-episodes, median age 79 years (IQR : 71-87 years), 42.4% female. Median temocillin course length was 5.9 days (IQR : 4.6-7.8 days). Indications for use: urinary tract infection (UTI) (=141), pneumonia (=53), other (=11). In total, 144 (70.2%) patients had targeted treatment; 74 (36.1%) against , 70 (34.4%) other Enterobacterales. A total of 130 (63%) patients received 4 g/day; the remaining patients had reduced renal function with dosing in accordance with guidance. Overall temocillin treatment success was 79.5%; highest when used to treat UTI 85.8% (versus 67.9% in respiratory infections, =0.008). Empirical treatment demonstrated 82.0% (50/61) success [versus 78.5% (113/144) among targeted treatment, =0. 71].

Conclusions: Temocillin at 4 g/day is an effective and safe alternative in treating patients with Gram-negative infections, but should be considered in the context of patient age and comorbidities. Increased dosing or alternate strategies may be indicated when the infection is not of a urinary source.
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http://dx.doi.org/10.1093/jacamr/dlab005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210019PMC
March 2021

Rapid diagnostic testing for antimicrobial stewardship: Utility in Asia Pacific.

Infect Control Hosp Epidemiol 2021 07 15;42(7):864-868. Epub 2021 Jun 15.

Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Rapid diagnostic testing (RDT) can provide prompt, accurate identification of infectious organisms and be a key component of antimicrobial stewardship (AMS) programs. However, their use is less widespread in Asia Pacific than western countries. Cost can be prohibitive, particularly in less resource-replete settings. A selective approach is required, possibly focusing on the initiation of antimicrobials, for differentiating bacterial versus viral infections and identifying locally relevant tropical diseases. Across Asia Pacific, more data are needed on RDT use within AMS, focusing on the impact on antimicrobial usage, patient morbidity and mortality, and cost effectiveness. Moreover, in the absence of formal guidelines, regional consensus statements to guide clinical practice are warranted. These will provide a regionally relevant definition for RDT; greater consensus on its role in managing infections; advice on implementation and overcoming barriers; and guidance on optimizing human resource capacity. By addressing these issues, the outcomes of AMS programs should improve.
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http://dx.doi.org/10.1017/ice.2021.149DOI Listing
July 2021

Bacteraemia variation during the COVID-19 pandemic; a multi-centre UK secondary care ecological analysis.

BMC Infect Dis 2021 Jun 11;21(1):556. Epub 2021 Jun 11.

Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH, UK.

Background: We investigated for change in blood stream infections (BSI) with Enterobacterales, coagulase negative staphylococci (CoNS), Streptococcus pneumoniae, and Staphylococcus aureus during the first UK wave of SARS-CoV-2 across five London hospitals.

Methods: A retrospective multicentre ecological analysis was undertaken evaluating all blood cultures taken from adults from 01 April 2017 to 30 April 2020 across five acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation.

Results: One hundred nineteen thousand five hundred eighty-four blood cultures were included. At the height of the UK SARS-CoV-2 first wave in April 2020, Enterobacterales bacteraemias were at an historic low across two London trusts (63/3814, 1.65%), whilst all CoNS BSI were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p = 0.013), CoNS central line associated BSIs (CLABSI) (p < 0.01) and CoNS non-CLABSI (p < 0.01), when compared with prior periods, even allowing for seasonal variation. S. pneumoniae (p = 0.631) and S. aureus (p = 0.617) BSI did not vary significant throughout the study period.

Conclusions: Significantly fewer than expected Enterobacterales BSI occurred during the UK peak of the COVID-19 pandemic; identifying potential causes, including potential unintended consequences of national self-isolation public health messaging, is essential. High rates of CoNS BSI, with evidence of increased CLABSI, but also likely contamination associated with increased use of personal protective equipment, may result in inappropriate antimicrobial use and indicates a clear area for intervention during further waves.
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http://dx.doi.org/10.1186/s12879-021-06159-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195453PMC
June 2021

Clinical Utility and Functionality of an Artificial Intelligence-Based App to Predict Mortality in COVID-19: Mixed Methods Analysis.

JMIR Form Res 2021 Jul 28;5(7):e27992. Epub 2021 Jul 28.

Chelsea and Westminster NHS Foundation Trust, London, United Kingdom.

Background: The artificial neural network (ANN) is an increasingly important tool in the context of solving complex medical classification problems. However, one of the principal challenges in leveraging artificial intelligence technology in the health care setting has been the relative inability to translate models into clinician workflow.

Objective: Here we demonstrate the development of a COVID-19 outcome prediction app that utilizes an ANN and assesses its usability in the clinical setting.

Methods: Usability assessment was conducted using the app, followed by a semistructured end-user interview. Usability was specified by effectiveness, efficiency, and satisfaction measures. These data were reported with descriptive statistics. The end-user interview data were analyzed using the thematic framework method, which allowed for the development of themes from the interview narratives. In total, 31 National Health Service physicians at a West London teaching hospital, including foundation physicians, senior house officers, registrars, and consultants, were included in this study.

Results: All participants were able to complete the assessment, with a mean time to complete separate patient vignettes of 59.35 (SD 10.35) seconds. The mean system usability scale score was 91.94 (SD 8.54), which corresponds to a qualitative rating of "excellent." The clinicians found the app intuitive and easy to use, with the majority describing its predictions as a useful adjunct to their clinical practice. The main concern was related to the use of the app in isolation rather than in conjunction with other clinical parameters. However, most clinicians speculated that the app could positively reinforce or validate their clinical decision-making.

Conclusions: Translating artificial intelligence technologies into the clinical setting remains an important but challenging task. We demonstrate the effectiveness, efficiency, and system usability of a web-based app designed to predict the outcomes of patients with COVID-19 from an ANN.
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http://dx.doi.org/10.2196/27992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320734PMC
July 2021

Optimising the initial investigation of suspected cases of SARS-CoV-2 reinfection.

Travel Med Infect Dis 2021 Jul-Aug;42:102078. Epub 2021 Apr 30.

Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH, UK; North West London Pathology, Fulham Palace Road, London, W6 8RF, UK; Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Du Cane Road, London, W12 0NN, UK.

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http://dx.doi.org/10.1016/j.tmaid.2021.102078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084632PMC
June 2021

SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (React 2): diagnostic accuracy study.

BMJ 2021 03 2;372:n423. Epub 2021 Mar 2.

Department of Infectious Disease, Imperial College London, School of Medicine, St Mary's Hospital, Praed Street, London W2 1NY, UK.

Objective: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national coronavirus disease 2019 (covid-19) seroprevalence programme (real time assessment of community transmission 2-React 2).

Design: Diagnostic accuracy study.

Setting: Laboratory analyses were performed in the United Kingdom at Imperial College, London and university facilities in London. Research clinics for finger prick sampling were run in two affiliated NHS trusts.

Participants: Sensitivity analyses were performed on sera stored from 320 previous participants in the React 2 programme with confirmed previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Specificity analyses were performed on 1000 prepandemic serum samples. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger prick testing.

Interventions: Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 serum samples from participants with confirmed SARS-CoV-2 infection and 500 prepandemic serum samples, respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger prick sensitivity of the LFIA currently used in React 2 seroprevalence studies (84%). These LFIAs were then further evaluated through finger prick testing on participants with confirmed previous SARS-CoV-2 infection: two LFIAs (Surescreen, Panbio) were evaluated in clinics in June-July 2020 and the third LFIA (AbC-19) in September 2020. A spike protein enzyme linked immunoassay and hybrid double antigen binding assay were used as laboratory reference standards.

Main Outcome Measures: The accuracy of LFIAs in detecting immunoglobulin G (IgG) antibodies to SARS-CoV-2 compared with two reference standards.

Results: The sensitivity and specificity of seven new LFIAs that were analysed using sera varied from 69% to 100%, and from 98.6% to 100%, respectively (compared with the two reference standards). Sensitivity on finger prick testing was 77% (95% confidence interval 61.4% to 88.2%) for Panbio, 86% (72.7% to 94.8%) for Surescreen, and 69% (53.8% to 81.3%) for AbC-19 compared with the reference standards. Sensitivity for sera from matched clinical samples performed on AbC-19 was significantly higher with serum than finger prick at 92% (80.0% to 97.7%, P=0.01). Antibody titres varied considerably among cohorts. The numbers of positive samples identified by finger prick in the lowest antibody titre quarter varied among LFIAs.

Conclusions: One new LFIA was identified with clinical performance suitable for potential inclusion in seroprevalence studies. However, none of the LFIAs tested had clearly superior performance to the LFIA currently used in React 2 seroprevalence surveys, and none showed sufficient sensitivity and specificity to be considered for routine clinical use.
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http://dx.doi.org/10.1136/bmj.n423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921617PMC
March 2021

A retrospective multicenter analysis of candidaemia among COVID-19 patients during the first UK pandemic wave.

J Infect 2021 06 18;82(6):276-316. Epub 2021 Feb 18.

Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London SW10 9NH, UK; North West London Pathology, Fulham Palace Road, London W6 8RF, UK; Imperial College London, Department of Infectious Diseases, Flowers Building, Armstrong Road, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.jinf.2021.02.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890346PMC
June 2021

Structured serological testing is an essential component to investigating SARS-CoV-2 reinfection.

Lancet Infect Dis 2021 05 20;21(5):598-599. Epub 2021 Jan 20.

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; North West London Pathology, London, UK; Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, London, UK.

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http://dx.doi.org/10.1016/S1473-3099(20)30990-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817473PMC
May 2021

Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis.

Eur J Hosp Pharm 2021 Jan 7. Epub 2021 Jan 7.

Microbiology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Introduction: Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced.

Methods: A retrospective case series of patients receiving oral antimicrobials (ciprofloxacin, levofloxacin and doxycycline) was analysed at a single-centre NHS acute hospital (April 2016-September 2019). Patient demographics, including concurrent enteral therapies, were recorded using medical records. Clinically important interactions were defined as doses administered within 2 hours of antimicrobial therapy.

Results: A total of 4067 prescriptions for the study antimicrobials (ciprofloxacin, n=1905; levofloxacin, n=538; and doxycycline, n=1624) were prescribed for 3584 patients. 1918/3583 (53.5%) of the patients were female, and the median age was 67 years (range 0.5-105.0 years). 810/4067 (19.3%) prescriptions reviewed had an interacting enteral therapy (calcium or iron salt) administered within 2 hours of the study medication.

Conclusion: The concomitant administration of enteral calcium and iron with oral antimicrobials is common within the acute care hospital setting. Approximately one in five patients has a clinically important interaction which may impair oral bioavailability and limit treatment efficacy. As antimicrobial stewardship teams strive for increased intravenous-to-oral de-escalation, it is important that optimum dosing administration is followed to optimise patient outcomes.
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http://dx.doi.org/10.1136/ejhpharm-2020-002445DOI Listing
January 2021

A pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, United Kingdom.

Mycoses 2021 Apr 24;64(4):394-404. Epub 2020 Dec 24.

Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), Nijmegen, The Netherlands.

Outbreaks of fungal infections due to emerging and rare species are increasingly reported in healthcare settings. We investigated a pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, UK. We aimed to determine route of healthcare-associated transmission and prevent additional infections. From July 2018 through February 2019, we detected a pseudo-outbreak of R. similis isolated from bronchoalveolar lavage (BAL) fluid samples collected from nine patients who had undergone bronchoscopy in a multispecialty teaching hospital, during a period of 8 months. Isolates were identified by MALDI-TOF mass spectrometry. Antifungal susceptibility testing was performed by EUCAST broth microdilution. To determine genetic relatedness among R. similis isolates, we undertook amplified fragment length polymorphism analysis. To determine the potential source of contamination, an epidemiological investigation was carried out. We reviewed patient records retrospectively and audited steps taken during bronchoscopy as well as the subsequent cleaning and decontamination procedures. Fungal cultures were performed on samples collected from bronchoscopes and automated endoscope washer-disinfector systems. No patient was found to have an infection due to R. similis either before or after bronchoscopy. One bronchoscope was identified to be used among all affected patients with positive fungal cultures. Physical damage was found in the index bronchoscope; however, no fungus was recovered after sampling of the affected scope or the rinse water of automated endoscope washer-disinfectors. Use of the scope was halted, and, during the following 12-month period, Rhinocladiella species were not isolated from any BAL specimen. All pseudo-outbreak isolates were identified as R. similis with high genetic relatedness (>90% similarity) on ALFP analysis. The study emphasises the emergence of a rare and uncommon black yeast R. similis, with reduced susceptibility to echinocandins, in a bronchoscope-related pseudo-outbreak with a potential water-related reservoir. Our findings highlight the importance of prolonged fungal culture and species-level identification of melanised yeasts isolated from bronchoscopy samples. Possibility of healthcare-associated transmission should be considered when R. similis is involved in clinical microbiology samples.
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http://dx.doi.org/10.1111/myc.13227DOI Listing
April 2021

Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes.

BMC Med Inform Decis Mak 2020 11 19;20(1):299. Epub 2020 Nov 19.

Chelsea and Westminster NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH, UK.

Background: Accurately predicting patient outcomes in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2.

Method: Between March 1 and April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: (1) a Cox regression model and (2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration.

Results: Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI) 73.8-91.1 and 90.0%, 95% CI 81.2-95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI 91.1-94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI 85.7-88.2), p = 0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively.

Conclusion: We demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.
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http://dx.doi.org/10.1186/s12911-020-01316-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676403PMC
November 2020

Detection of SARS-CoV-2 Antibodies in Kidney Transplant Recipients.

J Am Soc Nephrol 2020 12 29;31(12):2753-2756. Epub 2020 Oct 29.

Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom

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http://dx.doi.org/10.1681/ASN.2020081152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790204PMC
December 2020

Investigating the association between ethnicity and health outcomes in SARS-CoV-2 in a London secondary care population.

PLoS One 2020 28;15(10):e0240960. Epub 2020 Oct 28.

Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Hammersmith Campus, London, United Kingdom.

Background: Black, Asian and minority ethnic (BAME) populations are emerging as a vulnerable group in the severe acute respiratory syndrome coronavirus disease (SARS-CoV-2) pandemic. We investigated the relationship between ethnicity and health outcomes in SARS-CoV-2.

Methods And Findings: We conducted a retrospective, observational analysis of SARS-CoV-2 patients across two London teaching hospitals during March 1 -April 30, 2020. Routinely collected clinical data were extracted and analysed for 645 patients who met the study inclusion criteria. Within this hospitalised cohort, the BAME population were younger relative to the white population (61.70 years, 95% CI 59.70-63.73 versus 69.3 years, 95% CI 67.17-71.43, p<0.001). When adjusted for age, sex and comorbidity, ethnicity was not a predictor for ICU admission. The mean age at death was lower in the BAME population compared to the white population (71.44 years, 95% CI 69.90-72.90 versus, 77.40 years, 95% CI 76.1-78.70 respectively, p<0.001). When adjusted for age, sex and comorbidities, Asian patients had higher odds of death (OR 1.99: 95% CI 1.22-3.25, p<0.006).

Conclusions: BAME patients were more likely to be admitted younger, and to die at a younger age with SARS-CoV-2. Within the BAME cohort, Asian patients were more likely to die but despite this, there was no difference in rates of admission to ICU. The reasons for these disparities are not fully understood and need to be addressed. Investigating ethnicity as a clinical risk factor remains a high public health priority. Studies that consider ethnicity as part of the wider socio-cultural determinant of health are urgently needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240960PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592846PMC
November 2020

Near-patient SARS-CoV-2 molecular platforms: new-old tools for new-old problems.

Authors:
Luke S P Moore

Lancet Respir Med 2020 12 8;8(12):1161-1163. Epub 2020 Oct 8.

Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, UK; North West London Pathology, Imperial College Healthcare NHS Trust, London, UK; National Institute for Health Research Health Protection Research Unit in Healthcare-Associated Infections and Antimicrobial Resistance, Imperial College London, London, UK. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30451-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544442PMC
December 2020

Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study.

Lancet Microbe 2020 Nov 17;1(7):e300-e307. Epub 2020 Sep 17.

Department of Infectious Disease, Imperial College London, UK.

Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing.

Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (-gene, -gene, n1, n2 and n3) and human ribonuclease P () as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing.

Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86-98) with an overall specificity of 100% (99-100). The sensitivity of the test varied by group (self-referred healthcare workers 94% [95% CI 85-98]; patients in the emergency department 100% [48-100]; and hospital inpatient admissions 100% [29-100]). Specificity was consistent between groups (self-referred health-care workers 100% [95% CI 98-100]; patients in the emergency department 100% [69-100]; and hospital inpatient admissions 100% [96-100]). Point of care testing performance was similar during a period of high background prevalence of laboratory positive tests (25% [95% 20-31] in April, 2020) and low prevalence (3% [95% 1-9] in inpatient screening). Amplification of viral nucleocapsid (n1, n2, and n3) and envelope protein gene (e-gene) were most sensitive for detection of spiked SARS-CoV-2 RNA.

Interpretation: The CovidNudge platform was a sensitive, specific, and rapid point of care test for the presence of SARS-CoV-2 without laboratory handling or sample pre-processing. The device, which has been implemented in UK hospitals since May, 2020, could enable rapid decisions for clinical care and testing programmes.

Funding: National Institute of Health Research (NIHR) Imperial Biomedical Research Centre, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with Public Health England, NIHR Biomedical Research Centre Oxford, and DnaNudge.
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http://dx.doi.org/10.1016/S2666-5247(20)30121-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498257PMC
November 2020

Serological assays for delayed SARS-CoV-2 case identification - Author's reply.

Lancet Respir Med 2020 10 14;8(10):e74. Epub 2020 Sep 14.

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London, UK; North West London Pathology, London, UK.

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http://dx.doi.org/10.1016/S2213-2600(20)30406-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489942PMC
October 2020

COVID-19 and fungal superinfection.

Lancet Microbe 2020 Jul 3;1(3):e107. Epub 2020 Jul 3.

Chelsea and Westminster NHS Foundation Trust, London SW10 9NH, UK.

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http://dx.doi.org/10.1016/S2666-5247(20)30065-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333994PMC
July 2020

Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey.

Thorax 2020 12 12;75(12):1082-1088. Epub 2020 Aug 12.

Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.

Background: Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.

Methods: Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two 'in-house' ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum.

Findings: 95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%-99.8%).

Interpretation: LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430184PMC
December 2020

Prognostic Modeling of COVID-19 Using Artificial Intelligence in the United Kingdom: Model Development and Validation.

J Med Internet Res 2020 08 25;22(8):e20259. Epub 2020 Aug 25.

Chelsea and Westminster NHS Foundation Trust, London, United Kingdom.

Background: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency and the case fatality rate in the United Kingdom is significant. Although there appear to be several early predictors of outcome, there are no currently validated prognostic models or scoring systems applicable specifically to patients with confirmed SARS-CoV-2.

Objective: We aim to create a point-of-admission mortality risk scoring system using an artificial neural network (ANN).

Methods: We present an ANN that can provide a patient-specific, point-of-admission mortality risk prediction to inform clinical management decisions at the earliest opportunity. The ANN analyzes a set of patient features including demographics, comorbidities, smoking history, and presenting symptoms and predicts patient-specific mortality risk during the current hospital admission. The model was trained and validated on data extracted from 398 patients admitted to hospital with a positive real-time reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2.

Results: Patient-specific mortality was predicted with 86.25% accuracy, with a sensitivity of 87.50% (95% CI 61.65%-98.45%) and specificity of 85.94% (95% CI 74.98%-93.36%). The positive predictive value was 60.87% (95% CI 45.23%-74.56%), and the negative predictive value was 96.49% (95% CI 88.23%-99.02%). The area under the receiver operating characteristic curve was 90.12%.

Conclusions: This analysis demonstrates an adaptive ANN trained on data at a single site, which demonstrates the early utility of deep learning approaches in a rapidly evolving pandemic with no established or validated prognostic scoring systems.
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http://dx.doi.org/10.2196/20259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451108PMC
August 2020

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

Lancet Respir Med 2020 09 24;8(9):885-894. Epub 2020 Jul 24.

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

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.
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http://dx.doi.org/10.1016/S2213-2600(20)30315-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380925PMC
September 2020

Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case-control study.

J Glob Antimicrob Resist 2020 09 24;22:826-831. Epub 2020 Jul 24.

National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, Du Cane Road, London W12 0HS, UK; Imperial College Healthcare NHS Trust, London, UK.

Background: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting.

Method: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified.

Results: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting.

Conclusion: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.
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http://dx.doi.org/10.1016/j.jgar.2020.07.010DOI Listing
September 2020

Non-invasive saliva specimens for the diagnosis of COVID-19: caution in mild outpatient cohorts with low prevalence.

Clin Microbiol Infect 2020 Dec 18;26(12):1711-1713. Epub 2020 Jul 18.

North West London Pathology, Imperial College Healthcare NHS Trust, London, UK.

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http://dx.doi.org/10.1016/j.cmi.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367808PMC
December 2020
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