Publications
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Low R, Young K, Verani L, et al., 2022, Point-of-care testing for tetanus immunity: a systematic review and meta-analysis, Emergency Medicine Journal, Vol: 39, Pages: 771-778, ISSN: 1472-0205
BACKGROUND: The current standard of care for tetanus prophylaxis management in patients with open wounds likely results in overtreatment and unnecessary costs. Point-of-care immunochromatographic tests, known as Tetanus Quick Sticks (TQS), have been developed to qualitatively measure tetanus immunoglobulin levels. Multiple studies advocate their use in EDs. We aim to evaluate the diagnostic accuracy and cost-effectiveness of TQS to assess their relevance in frontline emergency care. METHODS: A systematic review was undertaken following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was conducted in MEDLINE, Embase, Global Health, The Health Management Information Consortium and The Cochrane Library. Studies were eligible if sensitivity, specificity or cost-efficacy of TQS was reported. At least two authors independently assessed and extracted data from each study. A meta-analysis was conducted to evaluate summary sensitivity and specificity estimates for TQS. RESULTS: 12 studies were suitable for inclusion (n=1 662 865 participants): 1 modelling and 11 prospective observational cohort studies. Eight studies assessed diagnostic accuracy; the summary estimate for sensitivity was 90% (95% CI, 89% to 90%) with specificity 97% (95% CI, 95% to 100%). Six studies investigated cost-efficacy, reporting lower healthcare costs when using TQS instead of the current method of vaccination history, due to a decrease in unnecessary tetanus vaccine and immunoglobulin administration. Based on the current NHS supply chain data, TQS use could save £173.05 per tetanus-prone patient. CONCLUSION: TQS could confer the greatest cost savings if used in combination with vaccination history in patients with tetanus-prone wounds. A quality assurance process is recommended prior to implementation of TQS in EDs.
Girometti N, Byrne R, Bracchi M, et al., 2022, Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis, Lancet Infectious Diseases, Vol: 22, Pages: 1321-1328, ISSN: 1473-3099
BackgroundHistorically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre.MethodsIn this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak.FindingsMonkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34–45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes.InterpretationAutochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosa
Heskin J, Belfield A, Milne C, et al., 2022, Transmission of monkeypox virus through sexual contact - A novel route of infection., Journal of Infection, Vol: 85, Pages: 334-363, ISSN: 0163-4453
Hughes S, Heard K, Mughal N, et al., 2022, Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis, European Journal of Hospital Pharmacy, Vol: 29, Pages: 280-283, 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.
Hughes S, Heard K, Mughal N, et al., 2022, Optimisation of antimicrobial dosing in patients with acute kidney injury; a single centre observational study, JAC-Antimicrobial Resistance, Vol: 4, Pages: 1-6, ISSN: 2632-1823
Introduction:Acute kidney injury (AKI) is a potential complication of systemic infection. Optimising antimicrobial dosing in this dynamic state can be challenging with sub- or supra-therapeutic dosing risking treatment failure or toxicity, respectively. Locally, unadjusted renal dosing for the first 48 hours of infection is recommended; this analysis aims to determine the outcomes associated with this dosing strategy.Methods:A retrospective cohort analysis was undertaken in patients treated for Gram-negative bacteraemia with concurrent non-filtration dependent AKI from a single-centre NHS acute hospital (April 2016-March 2020). Patient demographics, microbiology data, antimicrobial treatment and patient outcome (in-hospital mortality, and kidney function) were analysed. Results:647 episodes of Gram-negative bacteraemia (608 patients) were included; 305/608(50.2%) were male with median age 71years(range 18–100years). AKI was present in 235/647(36.3%); 78/647(12.1%) and 45/647(7.0%) having Kidney Disease Improving Global Outcomes (KDIGO)-defined injury(stage 2) or failure(stage 3), respectively. In-hospital 30-day mortality was 25/352(7.1%), 14/112(12.5%), 26/123(21.1%) and 11/60(18.3%) in patients with normal renal function, AKI stage 1, AKI stage ≥2 and established CKD, respectively. Recovery of renal function at day21 or discharge was present in 105/106 surviving patients presenting with AKI≥2. Time to recovery of AKI was similar in patients receiving full, low or no aminoglycoside (3days versus4days versus 3days, p=0.612) and those receiving full and low-dose beta-lactam (3days versus 5days, p=0.077).Conclusion:There is a high burden of AKI in patients with Gram-negative bacteraemia. Dose adjustments of beta-lactams may not be necessary in the first 48-hours of infection-induced AKI and single-dose aminoglycosides may be considered for early empiric coverage.
McKean AR, Williams GJ, Macneal P, et al., 2022, Paediatric paronychia: A single centre retrospective, microbiological analysis and national survey., J Plast Reconstr Aesthet Surg, Vol: 75, Pages: 2387-2440
Rawson TM, Brzeska-Trafny I, Maxfield R, et al., 2022, A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales infection, Journal of Global Antimicrobial Resistance, Vol: 29, Pages: 558-562, ISSN: 2213-7165
Background:In response to infection with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM producing Enterobacterales.Methods:Minimum inhibitory concentration (MIC) of clinical NDM producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of ATM breakpoint following the addition of CAZ/AVI was explored. A CAZ/AVI E-test/ATM disc method was compared to broth dilution.Results:Of 43 isolates, 33/43 (77%) isolates were ATM resistant (median [range] MIC=56 [16 – 512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4mg/L) in 29/33 (89%) of resistant isolates. Overall, the E-test/disc method correlated with findings from broth dilution in 35/43 (81%) of cases. E-test/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%.Conclusion:CAZ/AVI+ATM demonstrated significant synergy in most ATM resistant NDM producing Enterobacterales. The E-test/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory.
Heskin J, Pallett SJC, Al-Hindawi A, et al., 2022, Evaluating the performance characteristics of five lateral flow assays for the detection of the SARS-CoV-2 nucleocapsid antigen, Scientific Reports, Vol: 12, ISSN: 2045-2322
In response to the COVID-19 pandemic, lateral flow assays (LFAs) for the detection of SARS-CoV-2 antigen have been proposed as a complementary option to the more costly and time consuming reverse-transcriptase polymerase chain reaction (RT-PCR). We assessed five commercially available SARS-CoV-2 antigen detecting LFAs (ASSUT EUROPE (Rome, Italy), Besthree (Taizhou, China), Encode (Zhuhai, China), Fortress (Antrim UK), and Hughes Medical (Buckinghamshire, UK), using samples collected from hospitalised individuals with COVID-19 and compared these results against established RT-PCR assays with the aim of estimating test performance characteristics. We performed a diagnostic accuracy study of the five LFAs on 110 inpatients with confirmed COVID-19 and 75 COVID-19 negative control participants. Assay evaluation was performed using a modified version of each manufacturer’s protocol allowing for parallel testing of a single sample on multiple assays. Additional variables were studied including infection acquisition, oxygenation requirements at time of swabbing, and patient outcomes. The 110 patients were 48% (53) female, with mean age 67 years (range 26–100 years), and 77% (85) cases were community onset SARS-CoV-2. Across the five assays, sensitivity ranged from 64 (95% CI 53–73) to 76% (95% CI 65–85); Fortress performed best with sensitivity of 76% (95% CI 65–85). Specificity was high across all assays with 4/5 LFAs achieving 100%. LFA sensitivity was not dependant on RT-PCR cycle thresholds. SARS-CoV-2 antigen detecting LFAs may complement RT-PCR testing to facilitate early diagnosis and provide community testing strategies for identification of patients with COVID-19, however we find suboptimal test performance characteristics across a range of commercially available manufacturers, below WHO and MHRA pre-set sensitivity performance thresholds. With such variation in sensitivity between LFAs and PCR testing and between assay brands, we advi
Wong SMY, Handford C, Vermaak M, et al., 2022, Addressing high-risk antipoaching roles in Central Africa: lessons from delivery of remote advanced first-aid teaching for trauma care and snakebite first aid, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, Vol: 116, Pages: 381-385, ISSN: 0035-9203
Kousathanas A, Pairo-Castineira E, Rawlik K, et al., 2022, Whole genome sequencing reveals host factors underlying critical Covid-19, Nature, Vol: 607, Pages: 97-103, ISSN: 0028-0836
Critical Covid-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalisation2-4 following SARS-CoV-2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing in 7,491 critically-ill cases compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical Covid-19. We identify 16 new independent associations, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type antigen secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in critical disease. Mendelian randomisation provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5, CD209) and coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of Covid-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication, or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between critically-ill cases and population controls is highly efficient for detection of therapeutically-relevant mechanisms of disease.
Pallett SJC, Heskin J, Groppelli E, et al., 2022, Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants., Lancet Microbe, Vol: 3, Pages: e167-e167
Apisarnthanarak A, Kim HB, Moore LSP, et al., 2022, Utility and applicability of rapid diagnostic testing in antimicrobial stewardship in the Asia-Pacific region: a delphi consensus, Clinical Infectious Diseases, Vol: 74, Pages: 2067-2076, ISSN: 1058-4838
Rapid diagnostic tests (RDTs) facilitate fast and accurate identification of infectious disease microorganisms and are a valuable component of multimodal antimicrobial stewardship (AMS) programs but are currently underutilized in the Asia-Pacific region. An experienced group of infectious diseases clinicians, clinical microbiologists, and a clinical pharmacist used a modified Delphi consensus approach to construct 10 statements, aiming to optimize the utility and applicability of infection-related RDTs for AMS in the Asia-Pacific region. They provide guidance on definition, types, optimal deployment, measuring effectiveness, and overcoming key challenges. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to indicate the strength of the recommendation and the quality of the underlying evidence. Given the diversity of the Asia-Pacific region, the trajectory of RDT development will vary widely; the collection of local data should be prioritized to allow realization and optimization of the full benefits of RDTs in AMS.
Pallett SJ, Jones R, Abdulaal A, et al., 2022, Variability in detection of SARS-CoV-2-specific antibody responses following mild infection: a prospective multicentre cross-sectional study, London, United Kingdom, 17 April to 17 July 2020, Eurosurveillance, Vol: 27, ISSN: 1025-496X
IntroductionImmunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.AimsWe aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.MethodsA multicentre prospective cross-sectional study was undertaken (April–July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.ResultsWe included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2–89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).ConclusionSARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic indiv
Pallett SJC, Handford C, Wong SMY, et al., 2022, Necrosis and amputation following the bite of the Bibron's stiletto snake (Atractaspis bibronii) with a concise review of current literature, Tropical Doctor, Vol: 52, Pages: 142-146, ISSN: 0049-4755
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.
Heskin J, Pallett SJC, Mughal N, et al., 2022, Caution required with use of ritonavir-boosted PF-07321332 in COVID-19 management, LANCET, Vol: 399, Pages: 21-22, ISSN: 0140-6736
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- Citations: 40
Heskin J, Pallett SJC, Mughal N, et al., 2022, Healthcare worker perceptions of routine asymptomatic SARS-CoV-2 screening using lateral flow assays: A qualitative analysis across two London hospitals, JOURNAL OF INFECTION, Vol: 84, Pages: E26-E28, ISSN: 0163-4453
Al-Hindawi A, Abdulaal A, Rawson T, et al., 2021, COVID-19 prognostic models: a pro-con debate for machine learning vs traditional statistics, Frontiers in Digital Health, Vol: 3, Pages: 1-6, ISSN: 2673-253X
The SARS-CoV-2 virus causing the COVID-19 pandemic has had an unprecedented impact on healthcare requiring multi-disciplinary innovation and novel thinking to minimise impact and improve outcomes. Wide ranging disciplines have collaborated including diverse clinicians (radiology, microbiology, critical care) working increasingly closely with data-science. This has been leveraged through the democratisation of data-science with increasing availability of easy to access open datasets, tutorials, programming languages and hardware it is significantly easier to create mathematical models. To address the COVID-19 pandemic, such data-science has enabled modelling of the impact of the virus on the population and on individuals for diagnostic, prognostic, and epidemiological ends. This has led to two large systematic reviews on this topic that have highlighted the two different ways in which this feat has been attempted: one using classical statistics and the other using more novel machine learning techniques. In this review, we debate the relative strengths and weaknesses of each method towards the specific task of predicting COVID-19 outcomes
Rawson TM, Wilson R, Moore L, et al., 2021, Exploring the pharmacokinetics of phenoxymethylpenicillin (Penicillin-V) in adults: a healthy volunteer study, Open Forum Infectious Diseases, Vol: 8, Pages: 1-4, ISSN: 2328-8957
This healthy volunteer study aimed to explore Phenoxymethylpenicillin (Penicillin-V) pharmacokinetics (PK) to support the planning of large, dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentration was determined and a base population PK model were fitted to the data.
Burdett A, Toumazou C, Sahoo R, et 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”.
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.
Hernandez B, Herrero-Viñas P, Rawson TM, et al., 2021, Resistance trend estimation using regression analysis to enhance antimicrobial surveillance: a multi-centre study in London 2009-2016, Antibiotics, Vol: 10, Pages: 1-16, ISSN: 2079-6382
In the last years, there has been an increase of antimicrobial resistance rates around the world with the misuse and overuse of antimicrobials as one of the main leading drivers. In response to this threat, a variety of initiatives have arisen to promote the efficient use of antimicrobials. These initiatives rely on antimicrobial surveillance systems to promote appropriate prescription practices and are provided by national or global health care institutions with limited consideration of the variations within hospitals. As a consequence, physicians’ adherence to these generic guidelines is still limited. To fill this gap, this work presents an automated approach to performing local antimicrobial surveillance from microbiology data. Moreover, in addition to the commonly reported resistance rates, this work estimates secular resistance trends through regression analysis to provide a single value that effectively communicates the resistance trend to a wider audience. The methods considered for trend estimation were ordinary least squares regression, weighted least squares regression with weights inversely proportional to the number of microbiology records available and autoregressive integrated moving average. Among these, weighted least squares regression was found to be the most robust against changes in the granularity of the time series and presented the best performance. To validate the results, three case studies have been thoroughly compared with the existing literature: (i) Escherichia coli in urine cultures; (ii) Escherichia coli in blood cultures; and (iii) Staphylococcus aureus in wound cultures. The benefits of providing local rather than general antimicrobial surveillance data of a higher quality is two fold. Firstly, it has the potential to stimulate engagement among physicians to strengthen their knowledge and awareness on antimicrobial resistance which might encourage prescribers to change their prescription habits more willingly. Moreover, it pro
Valenti M, Ranganathan N, Moore LSP, et al., 2021, Listeria monocytogenes infections: presentation, diagnosis and treatment, British Journal of Hospital Medicine, Vol: 82, Pages: 1-7, ISSN: 0210-0258
Listeriosis is an infective complication that primarily affects pregnant women, patients at extremes of age or those with weakened immune systems. Ingestion of food contaminated with Listeria monocytogenes is the most common source of infection, causing self-limiting illness in immunocompetent hosts but associated with invasive infection and high mortality in high-risk patient groups. Milder illness presents as gastroenteritis with fever, diarrhoea, nausea and vomiting common in the 7 days post exposure. Invasive infection, characterised by bacteraemia and encephalitis, can develop in high-risk patients. Fetal loss is a major complication of listeriosis during pregnancy. Penicillin-based therapy (high dose penicillin or amoxicillin) in combination with gentamicin is advised for invasive infection; co-trimoxazole may be considered for patients intolerant to penicillin. Vulnerable individuals, notably pregnant women, should be counseled on appropriate preventative strategies including avoiding foods commonly contaminated with L. monocytogenes, such as soft ripened cheeses, pate, cooked chilled meats, unpasteurised milk, and ready to eat poultry unless thoroughly cooked.
Lamb G, Heskin J, Randell P, et 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, Vol: 83, Pages: 452-457, 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.
Hughes S, Mughal N, Moore L, 2021, Procalcitonin to guide antibacterial prescribing in patients hospitalised with COVID-19, Antibiotics, Vol: 10, Pages: 1-8, 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.
Murongazvombo AS, Jones RS, Rayment M, et 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.
Soriano A, Carmeli Y, Omrani AS, et al., 2021, Ceftazidime-avibactam for the treatment of serious gram-negative infections with limited treatment options: a systematic literature review, Infectious Diseases and Therapy, Vol: 10, Pages: 1989-2034, 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
Abdulaal A, Patel A, Al-Hindawi A, et 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
COVID-19 Host Genetics Initiative, 2021, Mapping the human genetic architecture of COVID-19, Nature, Vol: 600, Pages: 472-477, ISSN: 0028-0836
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Apisarnthanarak A, Kim HB, Moore L, et 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.
Rawson TM, Hernandez B, Moore L, et 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.
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