Imperial College London

DrLukeMoore

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 2732l.moore CV

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

146 results found

Burdett A, Toumazou C, Sahoo R, Mujan A, Hon T-K, Bedzo-Nutakor J, Casali N, Karvela M, Sohbati M, Cooke GS, Davies GW, Moore LSPet al., 2021, Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing, BMC Infectious Diseases, Vol: 21, Pages: 1-10, ISSN: 1471-2334

BackgroundAs 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.MethodWe 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.ResultsAcross 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.ConclusionWe 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”.

Journal article

Moore L, William H, Savarimuthu S, 2021, A rare case of Wiessella confusa endocarditis, Clinical Infection In Practice, Vol: 12, ISSN: 2590-1702

Background:Weissella confusa, a Gram positive coccobacillus, is a rare cause of human disease. They are vancomycin resistant, bile aesculin positive, lactic acid fermenters previously classified as members of the Leuconostoc and Lactobacillus genera. Among the 19 recognised species of Weissella, W. confusa is most frequently associated with human infection, however as its name suggests establishing its pathogenicity and correctly identifying it using traditional phenotypic testing platforms can be challenging.Case report:We present a case of W. confusa endocarditis in a male from Ghana where W. confusa is used in the fermenting process of commonly consumed food products. We discuss the microbiological diagnostic processes, including identification of this organism through use of matrix-assisted laser-desorption ionisation/time-of-flight (MALDI-ToF), and how the laboratory derived susceptibility tests were interpreted and applied to construct a successful therapeutic regime for infective endocarditis.Conclusions:We review the literature around cases of invasive W. confusa disease, contextualising this organism in terms of relevance to patients who are immunocompromised or who have indwelling vascular access devices.

Journal article

Hughes S, Mughal N, Moore L, 2021, Procalcitonin to guide antibacterial prescribing in patients hospitalised with COVID-19, Antibiotics, ISSN: 2079-6382

Abstract: Antibacterial prescribing in patients presenting with COVID-19 remains discordant to rates of bacterial co-infection. Implementing diagnostic tests to exclude bacterial infection may aid reduction in antibacterial prescribing. (1) Method: A retrospective observational analysis was un-dertaken of all hospitalised patients with COVID-19 across a single-site NHS acute Trust (London, UK) from 01/12/20–28/2/21. Electronic patient records were used to identify patients, clinical data, and outcomes. Procalcitonin (PCT) serum assays, where available on admission, were analysed against electronic prescribing records for antibacterial prescribing to determine relationships with a negative PCT result (<0.25 mg/L) and antibacterial course length. (2) Results: Antibacterial agents were initiated on admission in 310/624 (49.7%) of patients presenting with COVID-19. 33/74 (44.5%) patients with a negative PCT on admission had their treatment stopped within 24 h. 6/49 (12.2%) patients who had antibacterials started but a positive PCT had their treatment stopped. Microbiologically confirmed bacterial infection was low (19/594; 3.2%); no correlation was seen with PCT and culture positivity (p = 1). Lower mortality (15.6% vs. 31.4%; p = 0.049), length of hospital stay (7.9 days vs 10.1 days; p = 0.044), and intensive care unit (ICU) admission (13.9% vs 40.8%; p = 0.001) were seen among patients with low PCT. (3) Conclusion: This retrospective analysis of community acquired COVID-19 patients demonstrates the potential role of PCT in ex-cluding bacterial co-infection. A negative PCT on admission correlates with shorter antimicrobial courses, early cessation of therapy and predicts lower frequency of ICU admission. Low PCT may support decision making in cessation of antibacterials at the 48–72 h review.

Journal article

Pallett SJ, Handford C, Wong SM, West C, Moore LSet al., 2021, Necrosis and amputation following the bite of the Bibron's stiletto snake (Atractaspis bibronii) with a concise review of current literature., Trop Doct

Atractaspis bibronii are highly specialised snakes found across Southern Africa. Adapted for subterranean hunting of prey, snakes of the genus Atractaspis 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. Atractaspididae 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 A. bibronii 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.

Journal article

Murongazvombo AS, Jones RS, Rayment M, Mughal N, Azadian B, Donaldson H, Davies GW, Moore LS, Aiken AMet al., 2021, Association between SARS-CoV-2 exposure and antibody status among healthcare workers in two London hospitals: a cross-sectional study., Infection Prevention in Practice, Vol: 3, Pages: 100157-100157, ISSN: 2590-0889

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, P=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, P=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.

Journal article

Soriano A, Carmeli Y, Omrani AS, Moore LSP, Tawadrous M, Irani Pet al., 2021, Ceftazidime-avibactam for the treatment of serious gram-negative infections with limited treatment options: a systematic literature review, Infectious Diseases and Therapy, Pages: 1-46, ISSN: 2193-8229

IntroductionA 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.MethodsLiterature 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.ResultsSeventy-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.ConclusionThis review provides qualitative evidence of successful use of ceftazidime-avibactam for the

Journal article

Lamb G, Heskin J, Randell P, Mughal N, Moore LS, Jones R, Davies GW, Rayment Met al., 2021, Real-world evaluation of COVID-19 lateral flow device (LFD) mass-testing in healthcare workers at a London hospital; a prospective cohort analysis, Journal of Infection, ISSN: 0163-4453

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.

Journal article

Abdulaal A, Patel A, Al-Hindawi A, Charani E, Alqahtani S, Davies G, Mughal N, Moore Let al., 2021, Clinical utility and functionality of an artificial intelligence application to predict mortality in COVID-19: a mixed methods analysis., JMIR Formative Research, Vol: 5, Pages: 1-13, ISSN: 2561-326X

BackgroundThe 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 AI technology in the healthcare setting has been the relative inability to translate models into clinician workflow. Here we demonstrate the development of a COVID-19 outcome prediction application which utilises an ANN and assesses its usability in the clinical setting. MethodsUsability assessment was conducted on the application followed by a semi-structured 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 analysed using the thematic framework method, which allowed for the development of themes from the interview narratives.Participants Thirty-one Nation Health Service (NHS) physicians at a West London teaching hospital, including foundation doctors, senior house officers, registrars, and consultants.ResultsAll participants were able to complete the assessment, with a mean time to complete separate patient vignettes of 59.35 seconds (standard deviation (SD) = 10.35). Mean system usability scale (SUS) score was 91.94 (SD = 8.54), which corresponds with an adjective rating of “Excellent”. The clinicians found the application intuitive and easy to use, with the majority describing its predictions as a useful adjunct to their clinical practice. The main concern related to use of the application in isolation as opposed to in conjunction with other clinical parameters. However, most clinicians felt that the application could positively reinforce or validate their clinical judgement.ConclusionTranslating AI technologies into the clinical setting remains an important but challenging task. We demonstrate the effectiveness, efficiency, and system usability of a web application designed to predict COVID-19 patient outcomes from

Journal article

Apisarnthanarak A, Kim HB, Moore L, Xiao Y, Singh S, Doi Y, Kwa AL-H, Sri La Sri Ponnampalavanar S, Cao Q, Kim S-W, Lee H, Santanirand Pet al., 2021, Rapid diagnostic testing for antimicrobial stewardship: Utility in Asia Pacific, Infection Control and Hospital Epidemiology, Vol: 42, Pages: 864-868, ISSN: 0899-823X

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.

Journal article

Rawson TM, Hernandez B, Moore L, Herrero P, Charani E, Ming D, Wilson R, Blandy O, Sriskandan S, Toumazou C, Georgiou P, Holmes Aet al., 2021, A real-world evaluation of a case-based reasoning algorithm to support antimicrobial prescribing decisions in acute care, Clinical Infectious Diseases, Vol: 72, Pages: 2103-2111, ISSN: 1058-4838

BackgroundA locally developed Case-Based Reasoning (CBR) algorithm, designed to augment antimicrobial prescribing in secondary care was evaluated.MethodsPrescribing recommendations made by a CBR algorithm were compared to decisions made by physicians in clinical practice. Comparisons were examined in two patient populations. Firstly, in patients with confirmed Escherichia coli blood stream infections (‘E.coli patients’), and secondly in ward-based patients presenting with a range of potential infections (‘ward patients’). Prescribing recommendations were compared against the Antimicrobial Spectrum Index (ASI) and the WHO Essential Medicine List Access, Watch, Reserve (AWaRe) classification system. Appropriateness of a prescription was defined as the spectrum of the prescription covering the known, or most-likely organism antimicrobial sensitivity profile.ResultsIn total, 224 patients (145 E.coli patients and 79 ward patients) were included. Mean (SD) age was 66 (18) years with 108/224 (48%) female gender. The CBR recommendations were appropriate in 202/224 (90%) compared to 186/224 (83%) in practice (OR: 1.24 95%CI:0.392-3.936;p=0.71). CBR recommendations had a smaller ASI compared to practice with a median (range) of 6 (0-13) compared to 8 (0-12) (p<0.01). CBR recommendations were more likely to be classified as Access class antimicrobials compared to physicians’ prescriptions at 110/224 (49%) vs. 79/224 (35%) (OR: 1.77 95%CI:1.212-2.588 p<0.01). Results were similar for E.coli and ward patients on subgroup analysis.ConclusionsA CBR-driven decision support system provided appropriate recommendations within a narrower spectrum compared to current clinical practice. Future work must investigate the impact of this intervention on prescribing behaviours more broadly and patient outcomes.

Journal article

Denny S, Rawson T, Hart P, Satta G, Pallett S, Abdulaal A, Hughes S, Gilchrist M, Mughal N, Moore Let al., 2021, Bacteraemia variation during the COVID-19 pandemic; a multi-centre UK secondary care ecological analysis, BMC Infectious Diseases, Vol: 21, Pages: 1-9, ISSN: 1471-2334

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 –119,584 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.

Journal article

Denny S, Abdolrasouli A, Elamin T, Gonzalo X, Pallett S, Charani E, Patel A, Donaldson H, Hughes S, Armstrong-James D, Moore LS, Mughal Net al., 2021, A retrospective multicenter analysis of candidaemia among COVID-19 patients during the first UK pandemic wave, Journal of Infection, Vol: 82, Pages: 276-316, ISSN: 0163-4453

Journal article

Low R, Young K, Verani L, Cotton DT, Welman T, Moore L, Horwitz MDet al., 2021, Point of Care Testing for Tetanus Immunity: A Systematic Review, ASIT VIRTUAL SURGICAL SUMMIT, Publisher: OXFORD UNIV PRESS, ISSN: 0007-1323

Conference paper

Pallett SJC, Jones R, Randell P, Davies GW, Moore LSPet al., 2021, Structured serological testing is an essential component to investigating SARS-CoV-2 reinfection, Lancet Infectious Diseases, Vol: 21, Pages: 598-599, ISSN: 1473-3099

Journal article

Pallett SJ, Brown CS, Mughal N, Jones R, Randell P, Moore LSet al., 2021, Optimising the initial investigation of suspected cases of SARS-CoV-2 reinfection, Travel Medicine and Infectious Disease, Vol: 42, Pages: 102078-102078, ISSN: 1477-8939

Journal article

Abdolrasouli A, Gibani MM, de Groot T, Borman AM, Hoffman P, Azadian BS, Mughal N, Moore LSP, Johnson EM, Meis JFet al., 2021, A pseudo-outbreak of Rhinocladiella similis in a bronchoscopy unit of a tertiary care teaching hospital in London, United Kingdom., Mycoses: diagnosis, therapy and prophylaxis of fungal diseases, Vol: 64, Pages: 394-404, ISSN: 0933-7407

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

Journal article

Pallett SJC, Denny S, Patel A, Charani E, Mughal N, Stebbing J, Davies G, Moore Let al., 2021, Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population., Scientific Reports, Vol: 11, Pages: 1-8, ISSN: 2045-2322

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.

Journal article

Moshe M, Daunt A, Flower B, Simmons B, Brown JC, Frise R, Penn R, Kugathasan R, Petersen C, Stockmann H, Ashby D, Riley S, Atchison C, Taylor GP, Satkunarajah S, Naar L, Klaber R, Badhan A, Rosadas C, Marchesin F, Fernandez N, Sureda-Vives M, Cheeseman H, O'Hara J, Shattock R, Fontana G, Pallett SJC, Rayment M, Jones R, Moore LSP, Ashrafian H, Cherapanov P, Tedder R, McClure M, Ward H, Darzi A, Cooke GS, Barclay WS, On behalf of the REACT Study teamet al., 2021, SARS-CoV-2 lateral flow assays for possible use in national covid-19 seroprevalence surveys (REACT2): diagnostic accuracy study, BMJ: British Medical Journal, Vol: 372, Pages: 1-8, ISSN: 0959-535X

Objective: To evaluate the performance of new lateral flow immunoassays (LFIAs) suitable for use in a national COVID-19 seroprevalence programme (REACT2).Design: Laboratory sensitivity and specificity analyses were performed for seven LFIAs on a minimum of 200 sera from individuals with confirmed SARS-CoV-2 infection, and 500 pre-pandemic sera respectively. Three LFIAs were found to have a laboratory sensitivity superior to the finger-prick sensitivity of the LFIA currently used in REACT2 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 a third LFIA (AbC-19) in September, 2020. A Spike protein enzyme-linked immunoassay (S-ELISA) and hybrid double antigen binding assay (DABA) were used as laboratory reference standards.Setting: Laboratory analyses were performed at Imperial College, London and University facilities in London, UK. Research clinics for finger-prick sampling were run in two affiliated NHS trusts.Participants: Sensitivity analysis on sera were performed on 320 stored samples from previous participants in the REACT2 programme with confirmed previous SARS-CoV-2 infection. Specificity analysis was performed using 1000 pre-pandemic sera. 100 new participants with confirmed previous SARS-CoV-2 infection attended study clinics for finger-prick testing.Main outcome measures: The accuracy of LFIAs in detecting IgG antibodies to SARS-CoV-2 in comparison to two in-house ELISAs.Results: The sensitivity of seven new LFIAs using sera varied between 69% and 100% (vs S-ELISA/hybrid DABA). Specificity using sera varied between 99.6% and 100%. Sensitivity on finger-prick testing for Panbio, Surescreen and AbC-19 was 77% (CI 61.4 to 88.2), 86% (CI 72.7 to 94.8) and 69% (CI 53.8 to 81.3) respectively vs S-ELISA/hybrid DABA. Sensitivity for sera from matched clinical samples performe

Journal article

Heard K, Killington K, Mughal N, Moore L, Hughes Set al., 2021, Clinical outcomes of temocillin use for invasive Enterobacterales infections; a single centre retrospective analysis, Journal of Antimicrobial Chemotherapy, Vol: 3, Pages: 1-7, ISSN: 0305-7453

Background: With increasing frequency of resistant Gram-negative bacteria, temocillin has potential utility in reducing carbapenem use. The 2020 EUCAST guideline changes to temocillin breakpoints and reclassifies isolates with a minimum inhibitory concentration from 0.001-16mg/L as ‘susceptible, increased exposure’ necessitating 6g/day rather than the previous 4g/day, associated with significant cost implications.Objectives: We explore the clinical utility and treatment failure rate of temocillin at 4g/day dosing.Method: 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, no subsequent recrudescence of infection, occurring within 30days.Results: Temocillin was used in 205 eligible patient-episodes, median age 79years (IQR:71-87years), 42.4% female. Median temocillin course length 5.9days (IQR:4.6-7.8days). Indications for use: urinary tract infection (UTI) (n=141), pneumonia (n=53), other (n=11). 144 (70.2%) patients had targeted treatment; 74 (36.1%) against Escherichia coli, 70 (34.4%) other Enterobacterales. 130 (63%) patients received 4g/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, p=0.008). Empirical treatment demonstrated 82.0% (50/61) success (versus 78.5% (113/144) among targeted treatment, p=0. 71). Discussion: 4g/day temocillin is an effective and safe alternative in treating patients with Gram-negative infections, but should be considered in the context of patient age and co-morbidities. Increased dosing or alternate strategies may be indicated when the infection is not of a urinary source.

Journal article

Asumang J, Heard K, Troise O, Fahmy S, Mughal N, Moore L, Hughes Set al., 2021, Evaluation of a thrice weekly administration of teicoplanin in the outpatient setting; retrospective observational multi-centre study, JAC-Antimicrobial Resistance, Vol: 3, ISSN: 2632-1823

Introduction:The glycopeptide teicoplanin is commonly utilised 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.MethodsA retrospective, observational study was conducted at Chelsea & Westminster hospital (March 2018 – 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.ResultsA total of 82 patients treated with teicoplanin in the OPAT service where included; 53/82 receiving thrice weekly and 29/82 receiving once daily dosing. Mean teicoplanin trough levels were similar in both groups (26.2mg/L and 25.8mg/L in once daily and thrice weekly groups, p=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 (>90mL/min) was associated with lower teicoplanin serum concentrations (21.4mg/L[±10.1] versus 29.7mg/L[SD±14], p = 0.0178) in the thrice weekly dosed group but not with the once daily dosed group (mean 28.2mg/L[±9.4] versus 23.7mg/L[±9.9], p = 0.2201). ConclusionsThis 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.

Journal article

Hughes S, Heard K, Mughal N, Moore LSPet al., 2021, Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis., European Journal of Hospital Pharmacy, ISSN: 2047-9956

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.

Journal article

Rela M, Opel S, Williams S, Collins D, Martin K, Mughal N, Moore Let al., 2021, Operating Room Fomites as Potential Sources for Microbial Transmission in Burns Theatres, European Burn Journal, Vol: 2, Pages: 1-8, ISSN: 2673-1991

Background: Burn patients are susceptible to healthcare-associated infections. Contaminated surfaces play a role in microbial transmission. This study aimed to quantify the degree of contamination of burns theatre fomites during routine clinical use. Methods: The Patslide Patient Transfer Board (PAT slide) and operating table were investigated using two methods—bacterial swabs to culture viable organisms and adenosine triphosphate (ATP) swabs to measure biological material. Both items were sampled four times a day: before the first case, immediately after a case, immediately before the next case after cleaning and after the terminal clean. Results: Among 82 bacterial samples, four organisms were isolated, including Staphylococcus aureus, Enterobacter cloacae (E. cloacae) x2 and Pseudomonas aeruginosa (P. aeruginosa), all from the PAT slide. The E. cloacae persisted after cleaning. In 9/82 swabs, the ATP count was &gt;10 relative light units (RLU). In all cases where an organism was identified, the ATP count was &gt;10 RLU. Hence the sensitivity and specificity of ATP &gt; 10 RLU in detecting an organism were 100% and 94% respectively. Conclusions: Within burns theatres, there are instances of bacterial contamination on surfaces that persist despite cleaning. ATP luminometers as a point-of-care device may have a role in determining the cleanliness of surfaces, potentially minimizing onwards-bacterial transmission.

Journal article

McKean AR, Batten G, Macneal P, Rahman SM, Moore LSP, Horwitz MDet al., 2021, Utilising multiplex PCR technology for rapid microbial diagnosis in hand and upper limb infections, Journal of Plastic, Reconstructive & Aesthetic Surgery, Vol: 74, Pages: 223-243, ISSN: 1748-6815

Journal article

Moore LSP, 2020, Near-patient SARS-CoV-2 molecular platforms: new-old tools for new-old problems, The Lancet Respiratory Medicine, Vol: 8, Pages: 1161-1163, ISSN: 2213-2600

Journal article

Skolimowska K, Rayment M, Jones R, Madona P, Moore LSP, Randell Pet al., 2020, Non-invasive saliva specimens for the diagnosis of COVID-19: caution in mild outpatient cohorts with low prevalence, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 26, Pages: 1711-1713, ISSN: 1198-743X

Journal article

Rajput J, Moore LS, Mughal N, Hughes Set al., 2020, Evaluating the risk of hyperkalaemia and acute kidney injury with cotrimoxazole: a retrospective observational study, Clinical Microbiology and Infection, Vol: 26, Pages: 1651-1657, ISSN: 1198-743X

OBJECTIVES: Increasing antimicrobial resistance has renewed interest in older, less used antimicrobials. Cotrimoxazole shows promise; however hyperkalaemia and acute kidney injury (AKI) are potential complications. Identifying risk factors for, and quantification of, these events is required for safe-use. This study aims to evaluate predictors of cotrimoxazole-associated AKI and hyperkalaemia in a clinical setting. METHOD: Patients prescribed cotrimoxazole were identified using electronic-healthcare records over three years (01/04/2016-31/03/2019). Individual risk-factors were recognised. Serum creatinine and potassium trends were analysed over the subsequent 21-days. AKI and hyperkalaemic patients were classified using Kidney Disease Improving Global Outcomes (KDIGO) and laboratory criteria. Univariate and multiple logistic regression analyses were performed. RESULTS: Among 214 patients prescribed co-trimoxazole, 42 (19.6%, 95%CI 14.6-25.7%) met AKI criteria and 33 (15.4%, 95%CI 11.0-21.1%) developed hyperkalaemia. Low baseline eGFR (<60mls/min/1,73m2, OR=7.78, 95%CI 3.57-16.13, p<0.0001) and cardiac disorders (OR=2.40, 95%CI 1.17-4.82, p=0.011) predicted AKI, while low baseline eGFR (<60mls/min/1.73m2, OR=6.80, 95%CI 3.09-15.06, p<0.0001) and higher baseline serum potassium (p=0.001) predicted hyperkalaemia. Low-dose cotrimoxazole (<1920mg/day) was associated with lower AKI and hyperkalaemia risk (p=0.007 and 0.019, respectively). Early (within first 2-4 days of therapy) serum creatinine changes predicted AKI (OR=3.65, 95%CI 1.73-7.41, p=0.001), and early serum potassium changes predicted hyperkalaemia (>0.6mmol/l, OR=2.47, 95%CI 1.14-5.27, p=0.0236). CONCLUSIONS: Cotrimoxazole-associated AKI and hyperkalaemia is frequent and dose-dependent. Renal function, serum potassium and pre-existing cardiac disorders should be evaluated before prescribing cotrimoxazole. Serum creatinine and potassium monitoring within first 2-4 days of treatment

Journal article

Pallett SJC, Jones R, Pallett MA, Rayment M, Mughal N, Davies GW, Moore LSPet al., 2020, Characterising differential antibody response is integral to future SARS-CoV-2 serostudies, Journal of Infection, Vol: 81, Pages: E28-E30, ISSN: 0163-4453

Journal article

Denny S, Rawson T, Satta G, Pallett SJC, Abdulaal A, Hughes S, Gilchrist M, Mughal N, Moore Let al., 2020, Bacteraemia variation during the COVID-19 pandemic; a multi-centre UK secondary care ecological analysis., Publisher: Research Square

Objectives – 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 six 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 six acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation.Results –119,584 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 CoNS were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p=0.013) and CoNS (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 Enterobacteriales 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, presumably representing 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.

Working paper

Abdulaal A, Patel A, Charani E, Denny S, Alqahtani S, Davies G, Mughal N, Moore Let al., 2020, Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes, BMC Medical Informatics and Decision Making, Vol: 20, Pages: 1-11, ISSN: 1472-6947

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.MethodBetween March 1 - 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. ConclusionWe 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.

Journal article

Abdulaal A, Patel A, Charani E, Denny S, Alqahtani SA, Davies GW, Mughal N, Moore LSPet al., 2020, Comparison of deep learning with regression analysis in creating predictive models for SARS-CoV-2 outcomes

<jats:title>Abstract</jats:title> <jats:p>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.MethodBetween March 1 - 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. ConclusionWe 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, departmenta

Journal article

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