Publications
199 results found
Singh S, Nurek M, Mason S, et al., 2023, WHY STOP? A prospective observational vignette-based study to determine the cognitive-behavioural effects of rapid diagnostic PCR-based point-of-care test results on antibiotic cessation in ICU infections., BMJ Open, Vol: 13
OBJECTIVES: Point-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians' antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness). DESIGN: Observational cohort simulation study. SETTING: ICU. PARTICIPANTS: 70 ICU consultants/trainees working in UK-based teaching hospitals. METHODS: Clinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the 'improvement' case), clinico-biological worsening ('worsening'), clinical improvement/biological worsening ('discordant clin better'), clinical worsening/biological improvement ('discordant clin worse'). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence. MEASURES: Antibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette. RESULTS: A negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, χ2(1)=25.82, p<0.001, w=0.32) in all vignettes except improvement (already high), most notably in discordant clin worse (49% pre-POCT vs 74% post-POCT). In a linear regression, factors that significantly reduced clinicians' inclination to stop antibiotics were a worsening trajectory (b=-0.73 (-1.33, -0.14), p=0.015), initia
Pallett SJC, Trompeter A, Basarab M, et al., 2023, Multidrug-resistant infections in war victims in Ukraine, Lancet Infectious Diseases, Vol: 23, Pages: e270-e271, ISSN: 1473-3099
Baltas I, Gilchrist M, Koutoumanou E, et al., 2023, Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study, JAC-Antimicrobial Resistance, Vol: 5, Pages: 1-9, ISSN: 2632-1823
OBJECTIVES: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. METHODS: An online survey was sent to all infection consultants in NHS acute hospitals in England. RESULTS: The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. CONCLUSIONS: The 'subscription-type' model was viewed favourably by infection consultants in England.
Rayment M, Cole S, Heskin J, et al., 2023, Managing mpox using a remote monitoring service, JOURNAL OF INFECTION, Vol: 87, Pages: e36-e38, ISSN: 0163-4453
Pairo-Castineira E, Rawlik K, Bretherick AD, et al., 2023, Author Correction: GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19, Nature, Vol: 619, Pages: E61-E61, ISSN: 0028-0836
Boyd S, Pallett S, Moore L, 2023, Orthopaedic care in disasters: preparedness must extend to peri-operative infection surveillance, The Lancet, Vol: 402, Pages: 290-290, ISSN: 0140-6736
Boyd SE, Pallett SJC, Moore LSP, 2023, Orthopaedic preparedness for disasters must extend to infection surveillance, LANCET, Vol: 402, Pages: 290-290, ISSN: 0140-6736
Chan MS, Holloway R, King R, et al., 2023, An insurance value modeling approach that captures the wider value of a novel antimicrobial to health systems, patients, and the population., Journal of Health Economics and Outcomes Research, Vol: 10, Pages: 1-9, ISSN: 2327-2236
Background: Traditional health economic evaluations of antimicrobials currently underestimate their value to wider society. They can be supplemented by additional value elements including insurance value, which captures the value of an antimicrobial in preventing or mitigating impacts of adverse risk events. Despite being commonplace in other sectors, constituents of the impacts and approaches for estimating insurance value have not been investigated. Objectives: This study assessed the insurance value of a novel gram-negative antimicrobial from operational healthcare, wider population health, productivity, and informal care perspectives. Methods: A novel mixed-methods approach was used to model insurance value in the United Kingdom: (1) literature review and multidisciplinary expert workshops to identify risk events for 4 relevant scenarios: ward closures, unavoidable shortage of conventional antimicrobials, viral respiratory pandemics, and catastrophic antimicrobial resistance (AMR); (2) parameterizing mitigable costs and frequencies of risk events across perspectives and scenarios; (3) estimating insurance value through a Monte Carlo simulation model for extreme events and a dynamic disease transmission model. Results: The mean insurance value across all scenarios and perspectives over 10 years in the UK was £718 million, should AMR remain unchanged, where only £134 million related to operational healthcare costs. It would be 50%-70% higher if AMR steadily increased or if a more risk-averse view (1-in-10 year downside) of future events is taken. Discussion: The overall insurance value if AMR remains at current levels (a conservative projection), is over 5 times greater than insurance value from just the operational healthcare costs perspective, traditionally the sole perspective used in health budgeting. Insurance value was generally larger for nationwide or universal (catastrophic AMR, pandemic, and conventional antimicrobial shortages) rather than l
Pallett S, Heskin J, Keating F, et al., 2023, Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation, Communications Medicine, Vol: 3, Pages: 1-9, ISSN: 2730-664X
Background: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies.Methods: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82yrs, IQR 76-88yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. Results: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8–14.5) higher associated with hybrid immunity (p<0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p<0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p<0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p=0.003). Conclusions: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value
Ashfield T, Hughes S, Baltas I, et al., 2023, Overview of general antimicrobial prescribing guidance across NHS trusts in the United Kingdom: analysis of the Induction™ MicroGuide platform with a focus on hospital-acquired pneumonia (HAP) disease definitions, Publisher: OXFORD UNIV PRESS
Bhaskar K, Clarke S, Moore L, et al., 2023, Bacterial peritonitis in paediatric appendicitis; microbial epidemiology and antimicrobial management, Annals of Clinical Microbiology and Antimicrobials, Vol: 22, ISSN: 1476-0711
Background: Appendicitis remains a common surgical emergency in children. Empirical antibacterial treatment is indicated to reduce infective complications. We investigate the bacterial pathogens identified intra-operatively during appendectomies in children to guide empirical surgical antimicrobial prophylaxis options.Methods: A retrospective analysis of patients (<18 years old) undergoing an appendectomy across a multisite London hospital (Nov2019-March2022) was undertaken. Patient-related outcomes including length of hospital stay (LOS), days of antibacterial therapy (DOT), intra-operative microbiology and post-operative radiology reports were interrogated. Results: 304 patients underwent an appendectomy during this period; 39.1% of patients had intraoperative samples cultured. Bacterial pathogens were found in 73/119 (61.3%) cases; the most common isolates being Escherichia coli (42.0%), Pseudomonas aeruginosa (21.0%), Streptococcus milleri. (14.3%) and Bacteroides fragilis (5.9%). Polymicrobial infection was common (32/73). Isolation of Pseudomonas spp. from intra-operative sampling was associated with a greater LOS (7.0 vs 5.0 days; p=0.011) but nil effect on the incidence of postoperative collections. Presence of Streptococcus milleri was associated with longer LOS (7.0 vs 5.0 day; p=0.007), DOT (12.0 vs 8.5 day; p=0.007) but had no observed outcome on postoperative collections (29.4% vs 18.6%; p=0.330). 48% of E. coli positive cultures were co-amoxiclav resistant and prolonged LOS compared to the non-resistant group (7.0 vs 5.0 days; p=0.040) but had no difference in post-operative collections (29.2% vs 17.9%; p=0.260).Conclusion: A high proportion of children with appendicitis have Pseudomonas spp. isolated, leading to a prolonged LOS. Evolving Enterobacterales resistance and the presence of Pseudomonas spp. necessitate extended antibacterial coverage for paediatric appendectomies with evidence of peritonitis
Moore L, Villegas MV, Wenzler E, et al., 2023, Rapid diagnostic test value and implementation in antimicrobial stewardship across low-to-middle and high-income countries: a mixed-methods review, Infectious Diseases and Therapy, Vol: 12, Pages: 1445-1463, ISSN: 2193-8229
Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.
Rawson TM, Moore LSP, 2023, Understanding how diagnostics influence antimicrobial decision-making is key to successful clinical trial design, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 29, Pages: 666-669, ISSN: 1198-743X
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Pallett S, Charani E, Hawkins L, et al., 2023, National action plans for antimicrobial resistance and variations in surveillance data platforms, Bulletin of the World Health Organization, Vol: 101, Pages: 501-512F, ISSN: 0042-9686
Objective To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization’s (WHO’s) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO’s Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control’s (ECDC’s) network and Pfizer’s Antimicrobial Testing Leadership and Surveillance database. Using Bland–Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer’s database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO’s and Pfizer’s platforms for organism–country susceptibility data ranged from −26% to 35%. While mean susceptibilities of WHO’s and ECDC‘s platforms did not differ (bias: 0%, 95% confidence interval: −2 to 2), concordance between organism–country susceptibility was low (limits of agreement −18 to 18%). Significant differences exist in isolate numbers reported between WHO–Pfizer (mean of difference: 674, P-value: < 0.001 and WHO–ECDC (mean of difference: 192, P value: 0.04) platforms. Conclusion The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and
Pairo-Castineira E, Rawlik K, Bretherick AD, et al., 2023, GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19, Nature, Vol: 617, Pages: 764-768, ISSN: 0028-0836
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
Rawson TM, Antcliffe D, Wilson R, et al., 2023, Management of bacterial and fungal infections in the ICU: diagnosis, treatment, and prevention recommendations, Infection and Drug Resistance, Vol: 16, Pages: 2709-2726, ISSN: 1178-6973
Bacterial and fungal infections are common issues for patients in the intensive care unit (ICU). Large, multinational point prevalence surveys have identified that up to 50% of ICU patients have a diagnosis of bacterial or fungal infection at any one time. Infection in the ICU is associated with its own challenges. Causative organisms often harbour intrinsic and acquired mechanisms of drug-resistance, making empiric and targeted antimicrobial selection challenging. Infection in the ICU is associated with worse clinical outcomes for patients. We review the epidemiology of bacterial and fungal infection in the ICU. We discuss risk factors for acquisition, approaches to diagnosis and management, and common strategies for the prevention of infection.
Pallett SJC, Heskin J, Keating F, et al., 2023, Risk of omicron infection for high-risk older adults in long-term care facilities, LANCET INFECTIOUS DISEASES, Vol: 23, Pages: 526-527, ISSN: 1473-3099
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Shah PL, Orton CM, Grinsztejn B, et al., 2023, Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care, LANCET RESPIRATORY MEDICINE, Vol: 11, Pages: 415-424, ISSN: 2213-2600
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Fink DL, Callaby H, Luintel A, et al., 2023, Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study., Lancet Infectious Diseases, Vol: 23, Pages: 589-597, ISSN: 1473-3099
BACKGROUND: The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. METHODS: In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. FINDINGS: 156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30-44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3 (IQR 349-828).
Charani ESMITA, Mendelson M, Pallett S, et al., 2023, An analysis of existing National Action Plans for antimicrobial resistance – gaps and opportunities in strategies optimising antibiotic use in human populations, The Lancet Global Health, Vol: 11, Pages: e466-e474, ISSN: 2214-109X
At the 2015 World Health Assembly, UN member states adopted a resolution that committed to the development of national action plans (NAPs) for antimicrobial resistance (AMR). The political determination to commit to NAPs and the availability of robust governance structures to assure sustainable translation of the identified NAP objectives from policy to practice remain major barriers to progress. Inter-country variability in economic and political resilience and resource constraints could be fundamental barriers to progressing AMR NAPs. Although there have been regional and global analyses of NAPs from a One Health and policy perspective, a global assessment of the NAP objectives targeting antimicrobial use in human populations is needed. In this Health Policy, we report a systematic evidence synthesis of existing NAPs that are aimed at tackling AMR in human populations. We find marked gaps and variability in maturity of NAP development and operationalisation across the domains of: (1) policy and strategic planning; (2) medicines management and prescribing systems; (3) technology for optimised antimicrobial prescribing; (4) context, culture, and behaviours; (5) operational delivery and monitoring; and (6) patient and public engagement and involvement. The gaps identified in these domains highlight opportunities to facilitate sustainable delivery and operationalisation of NAPs. The findings from this analysis can be used at country, regional, and global levels to identify AMR-related priorities that are relevant to infrastructure needs and contexts.
Heskin J, Dickinson M, Brown N, et al., 2023, Rapid reconfiguration of sexual health services in response to UK autochthonous transmission of mpox (monkeypox), Sexually Transmitted Infections, Vol: 99, Pages: 81-84, ISSN: 1368-4973
Goodfellow JJ, Hughes S, Smith J, et al., 2023, Novel use of oral chloramphenicol for treatment-resistant <i>Mycoplasma genitalium</i>, SEXUALLY TRANSMITTED INFECTIONS, ISSN: 1368-4973
Mistry R, Rawson T, Troise O, et al., 2022, Haematological and hepatic adverse effects of ceftriaxone in ambulatory care: a dual-centre retrospective observational analysis of standard vs high dose, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
BackgroundEuropean Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4g/day) rather than standard dose (2g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients. MethodAdult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher’s exact test used to identify statistical significance.ResultsIncidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2g group vs 6/39 (15.4%) in the 4g group (OR 0.89 (95% CI 0.26-2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2g and 4g groups respectively. Thrombocytopenia was observed in 0/47 in the 2g group compared with 3/39 (7.7%) in the 4g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2g and 4g respectively (OR 0.45 (95% CI 0.87 – 2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2g and 3/39 (7.7%) for 4g (OR 1.86 (95% CI 0.36 – 10.92), p 0.655).ConclusionsIncreased adverse effects with 4g (over 2g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute developm
Saeed K, Ahmad-Saeed N, Annett R, et al., 2022, A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel, European Journal of Clinical Microbiology and Infectious Diseases: an international journal on pathogenesis, diagnosis, epidemiology, therapy, and prevention of infectious diseases, Vol: 42, Pages: 169-176, ISSN: 0934-9723
Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI.
Hussain K, Bandyopadhyay A, Roberts N, et al., 2022, Panton-Valentine leucocidin-producing Staphylococcus aureus: a clinical review, Clinical and Experimental Dermatology, Vol: 47, Pages: 2150-2158, ISSN: 0307-6938
Panton-Valentine leucocidin (PVL) is a virulence factor produced by certain strains of Staphylococcus aureus (SA). Through its cytolytic action on the cell membranes of human polymorphonuclear neutrophils, PVL causes a range of pathologies collectively known as PVL-SA disease. The hallmark clinical signs of PVL-SA are recurrent boils and necrotizing skin and soft tissue infections (SSTIs) in otherwise healthy patients; however, it can lead to more severe and invasive presentations, including necrotizing haemorrhagic pneumonia, necrotizing fasciitis and purpura fulminans. Young adults with minimal previous exposure to healthcare settings tend to be at highest risk for acquiring PVL-SA disease, with close physical contact playing a central role in disease transmission. The prevalence of PVL-SA varies globally; however, this is often underestimated owing to a lack of routine PVL testing. In the UK, PVL-positive SA isolates have been rising over the past decade alongside an increasing prevalence of multidrug resistance in larger cities. This review article aims to raise awareness of the PVL toxin, to aid clinicians with diagnostic pointers and to provide guidance with treatment, with an emphasis on the need for further population-based studies.
Chan MS, Holloway R, King R, et al., 2022, THE BENEFITS THAT A NOVEL ANTIMICROBIAL PROVIDES WHEN VIEWED FROM AN INSURANCE VALUE PERSPECTIVE, Publisher: ELSEVIER SCIENCE INC, Pages: S297-S297, ISSN: 1098-3015
Enne V, Aydin A, Baldan R, et al., 2022, Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study, Thorax, Vol: 77, Pages: 1220-1228, ISSN: 0040-6376
Background Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship.Methods Surplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology.Findings In 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%–100.0% and specificity of 87.5%–99.5%; Unyvero had sensitivity of 50.0%–100.0%%, and specificity of 89.4%–99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%.Interpretation Conventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential
Pallett SJC, Rayment M, Heskin J, et al., 2022, Early identification of high-risk individuals for monoclonal antibody therapy and prophylaxis is feasible by SARS-CoV-2 anti-spike antibody specific lateral flow assay, Diagnostic Microbiology and Infectious Disease, Vol: 104, ISSN: 0732-8893
Monoclonal antibody therapy has been approved for prophylaxis and treatment of severe COVID-19 infection. Greatest benefit appears limited to those yet to mount an effective immune response from natural infection or vaccination, but concern exists around ability to make timely assessment of immune status of community-based patients where laboratory-based serodiagnostics predominate. Participants were invited to undergo paired laboratory-based (Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle immunoassay) and lateral flow assays (LFA; a split SARS-CoV-2 IgM/IgG and total antibody test) able to detect SARS-CoV-2 anti-spike antibodies. LFA band strength was compared with CMIA titer by log-linear regression. Two hundred individuals (median age 43.5 years, IQR 30-59; 60.5% female) underwent testing, with a further 100 control sera tested. Both LFA band strengths correlated strongly with CMIA antibody titers (P < 0.001). LFAs have the potential to assist in early identification of seronegative patients who may demonstrate the greatest benefit from monoclonal antibody treatment.
Singh S, Ark R, Tatlock J, et al., 2022, Evaluating the long-term impact of an antimicrobial stewardship programme in a central London mixed medical and surgical intensive care unit, JAC-Antimicrobial Resistance, Vol: 4, ISSN: 2632-1823
Background:Antimicrobial overuse causes increased antimicrobial resistance in ICUs; antimicrobial stewardship programmes (ASPs) aim to optimize usage. Following an MDR Acinetobacter baumannii (MRAb) outbreak in 2008, an ASP was implemented at a London ICU, and then continued as a long-term programme. This study aimed to determine long-term changes in antimicrobial prescribing 9 years on.Methods:Data were collected from ICU patients in 2008 immediately before ASP implementation, and thereafter for 6 month cohort periods in 2010–2011, 2012 and 2017. Antimicrobial usage in DDD per 1000 occupied bed days (OBD) were compared. Multivariate linear regression models for antimicrobial days were fitted, adjusting for APACHE II score and patient days. Antimicrobial resistance in Pseudomonas aeruginosa (as an indicator organism) was compared across cohort periods.Findings:Across 400 patients over 9 years, antimicrobial use changed significantly (P < 0.011) and remained lower in all post-ASP cohorts compared with pre-ASP [(2008; 1827 DDD/1000 OBD), (2010; 1264 DDD/1000 OBD), (2012; 1270 DDD/1000 OBD) and (2017; 1566 DDD/1000 OBD)]. There was reduction in usage of all antimicrobial classes except β-lactams (where there was no significant increase nor decrease, P = 0.178) and aminoglycosides (where there was a significant increase in usage, P < 0.0001). The latter was temporally associated with restrictions on specific carbapenems. There was an increase in carbapenem-resistant P. aeruginosa in 2012 only (P = 0.028) but not subsequently.Conclusions:Following ASP implementation after an outbreak of MRAb, reduced antimicrobial prescribing was maintained 9 years on. We identify several factors influencing successful long-term maintenance of ASPs in ICUs.
Singh S, Moore LSP, Mughal N, et al., 2022, Novel inhaled antifungal for pseudomembranous Aspergillus tracheobronchitis complicating connective tissue disease, Thorax, Vol: 78, Pages: 110-111, ISSN: 0040-6376
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