63 results on '"Sandoe JAT"'
Search Results
2. Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms
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Caudwell, JA, Tinkler, JM, Johnson, BRG, McDowell, KJ, Alsulaimani, F, Tiede, C, Tomlinson, DC, Freear, S, Turnbull, B, Evans, SD, and Sandoe, JAT
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Cell Biology ,Molecular Biology ,Applied Microbiology and Biotechnology ,Microbiology - Abstract
Staphylococcus aureus (S. aureus) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor – a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (KD = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 μL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment.
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- 2022
3. Pasteurella multocida Endocarditis with Septic Arthritis: Case Report and Review of the Literature
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Carter, E, primary, Iroegbu, U, additional, Baig, W, additional, and Sandoe, JAT, additional
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- 2021
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4. Infective endocarditis in the adult patient
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Sandoe, JAT, primary, Watkin, RW, additional, and Dayer, MJ, additional
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- 2021
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5. Production of Giant Unilamellar Vesicles and Encapsulation of Nematic Lyotropic Liquid Crystals
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Bao, P, Paterson, DA, Peyman, SA, Jones, JC, Sandoe, JAT, Gleeson, HF, Evans, SD, and Bushby, RJ
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We describe a modified microfluidic method for making Giant Unilamellar Vesicles (GUVs)viawater/octanol-lipid/water double emulsion droplets. At a high enough lipid concentration we show that thede-wetting of the octanol from these droplets occurs spontaneously (off-chip) without the need to useshear to aid the de-wetting process. The resultant mixture of octanol droplets and GUVs can beseparated by making use of the buoyancy of the octanol. A simpler microfluidic device and pumpsystem can be employed and, because of the higher flow-rates and much higher rate of formation ofthe double emulsion droplets (B1500 s 1compared to up toB75 s 1), it is easier to make largernumbers of GUVs and larger volumes of solution. Because of the potential for using GUVs thatincorporate lyotropic nematic liquid crystals in biosensors we have used this method to make GUVs thatincorporate the nematic phases of sunset yellow and disodium chromoglycate. However, the phasebehaviour of these lyotropic liquid crystals is quite sensitive to concentration and we found that there isan unexpected spread in the concentration of the contents of the GUVs obtained.
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- 2021
6. 6 - Principles of infectious disease
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Sandoe, JAT and Dockrell, DH
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- 2023
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7. Penicillin allergy de-labelling ahead of elective surgery: feasibility and barriers
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Savic, L, Gurr, L, Kaura, V, Toolan, J, Sandoe, JAT, Hopkins, PM, and Savic, S
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Background: Around 10–15% of the in-patient population carry unsubstantiated ‘penicillin allergy’ labels, the majority incorrect when tested. These labels are associated with harm from use of broad-spectrum non-penicillin antibiotics. Current testing guidelines incorporate both skin and challenge tests; this is prohibitively expensive and time-consuming to deliver on a large scale. We aimed to establish the feasibility of a rapid access de-labelling pathway for surgical patients, using direct oral challenge. Methods: ‘Penicillin allergic’ patients, recruited from a surgical pre-assessment clinic, were risk-stratified using a screening questionnaire. Patients at low risk of true, immunoglobulin E (IgE)-mediated allergy were offered direct oral challenge using incremental amoxicillin to a total dose of 500 mg. A 3-day course was completed at home. De-labelled patients were followed up to determine antibiotic use in surgery, and attitudes towards de-labelling were explored. Results: Of 219 patients screened, 74 were eligible for inclusion and offered testing. We subsequently tested 56 patients; 55 were de-labelled. None had a serious reaction to the supervised challenge, or thereafter. On follow-up, 17 of 19 patients received appropriate antimicrobial prophylaxis during surgery. Only three of 33 de-labelled patients would have been happy for the label to be removed without prior specialist testing. Conclusion: Rapid access de-labelling, using direct oral challenge in appropriately risk-stratified patients, can be incorporated into the existing surgical care pathway. This provides immediate and potential long-term benefit for patients. Interest in testing is high among patients, and clinicians appear to follow clinic recommendations. Patients are unlikely to accept removal of their allergy label on the basis of history alone.
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- 2019
8. Oral versus intravenous antibiotics for bone and joint infection
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John Marshall, Gavin Barlow, A S Walker, S C Ellis, Abtin Alvand, Lucinda Barrett, Susan Hopkins, Jennifer Bostock, Philippa C Matthews, John Paul, D J Bunn, Adrian Taylor, Claudia Geue, E Khatamzas, Parham Sendi, S Warren, M Rogers, B Atkins, Rhea Zambellas, S Stafford, C E Moran, Sandoe Jat., I. Byren, Graham S Cooke, N. Jenkins, M Scarborough, R K Sutherland, Andrew Brent, Harriet Hughes, C Vallance, Helen Reynolds, Guy E. Thwaites, A F Woodhouse, J Folb, Benjamin A. Lipsky, I Aggarwal, C Scarborough, Tri Wangrangsimakul, R.A. Seaton, Wong Thn., F E Fitzgerald, Roger Gundle, C F Old, Cyrus Cooper, Michelle Kümin, Anthony R. Berendt, K Bisnauthsing, Ines Rombach, Andrew Briggs, Martin A. McNally, Mack Djf., Nicola McMeekin, Elinoor Moore, J Lomas, Philip Bejon, Brian Angus, Li H-K., C J Hemsley, D Bose, and National Institute for Health Research
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Treatment outcome ,Medication adherence ,Administration, Oral ,030204 cardiovascular system & hematology ,Article ,law.invention ,Medication Adherence ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Medicine, General & Internal ,Randomized controlled trial ,law ,Internal medicine ,General & Internal Medicine ,OSTEOMYELITIS ,medicine ,MANAGEMENT ,Humans ,030212 general & internal medicine ,610 Medicine & health ,Aged ,Aged, 80 and over ,Intention-to-treat analysis ,Science & Technology ,business.industry ,General Medicine ,11 Medical And Health Sciences ,Middle Aged ,Bone Diseases, Infectious ,Anti-Bacterial Agents ,Intention to Treat Analysis ,Editorial Commentary ,Treatment Outcome ,Multicenter study ,Intravenous antibiotics ,Oral antibiotic therapy ,Orthopedic surgery ,570 Life sciences ,biology ,OVIVA Trial Collaborators ,Administration, Intravenous ,Female ,Joint Diseases ,business ,Life Sciences & Biomedicine - Abstract
BACKGROUND\ud \ud The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.\ud \ud \ud \ud METHODS\ud \ud We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points.\ud \ud \ud \ud RESULTS\ud \ud Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%).\ud \ud \ud \ud CONCLUSIONS\ud \ud Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927. opens in new tab.)
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- 2018
9. 6 - Principles of infectious disease
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Sandoe, JAT and Dockrell, DH
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- 2018
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10. Efficacy of rifampicin combination therapy for the treatment of enterococcal infections assessed in vivo using a Galleria mellonella infection model.
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Skinner, K, Sandoe, JAT, Rajendran, R, Ramage, G, Lang, S, Skinner, K, Sandoe, JAT, Rajendran, R, Ramage, G, and Lang, S
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Enterococci are a leading cause of healthcare-associated infection worldwide and display increasing levels of resistance to many of the commonly used antimicrobials, making treatment of their infections challenging. Combinations of antibiotics are occasionally employed to treat serious infections, allowing for the possibility of synergistic killing. The aim of this study was to evaluate the effects of different antibacterial combinations against enterococcal isolates using an in vitro approach and an in vivo Galleria mellonella infection model. Five Enterococcus faecalis and three Enterococcus faecium strains were screened by paired combinations of rifampicin, tigecycline, linezolid or vancomycin using the chequerboard dilution method. Antibacterial combinations that displayed synergy were selected for in vivo testing using a G. mellonella larvae infection model. Rifampicin was an effective antibacterial enhancer when used in combination with tigecycline or vancomycin, with minimum inhibitory concentrations (MICs) of each individual antibiotic being reduced by between two and four doubling dilutions, generating fractional inhibitory concentration index (FICI) values between 0.31 and 0.5. Synergy observed with the chequerboard screening assays was subsequently observed in vivo using the G. mellonella model, with combination treatment demonstrating superior protection of larvae post-infection in comparison with antibiotic monotherapy. In particular, rifampicin in combination with tigecycline or vancomycin significantly enhanced larvae survival. Addition of rifampicin to anti-enterococcal treatment regimens warrants further investigation and may prove useful in the treatment of enterococcal infections whilst prolonging the clinically useful life of currently active antibiotics.
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- 2017
11. The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in 7 NHS secondary care hospitals in England: a series of local service evaluations
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Goldenberg, SD, Brown, S, Edwards, L, Gnanarajah, D, Howard, P, Jenkins, D, Nayar, D, Pasztor, M, Oliver, S, Planche, T, Sandoe, JAT, Wade, P, and Whitney, L
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genetic structures - Abstract
Purpose. C. difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the NHS and Public Health England alike. In June 2012 fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real world data to understand the effectiveness of fidaxomicin in routine practice. Methods. In 7 hospitals introducing FDX between July 2012-July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18yrs with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment anytime within 3 months after the first episode. Results. Each hospital had a different protocol for use of fidaxomicin. In hospitals A and B, where fidaxomicin was used first line for all primary and recurrent episodes, recurrence rate reduced from 10.6% to 3.1% and from 16.3% to 3.1%, with a significant difference in 28-day mortality from 18.2% to 3.1% (P
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- 2016
12. Prepatellar bursitis: a rare manifestation of chronic brucellosis
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Mawer, DPC, McGann, PH, Sandoe, JAT, Emerton, M, Beeching, NJ, and Wilcox, MH
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Introduction: Bursitis is a rare complication of brucellosis that has only once been described in a country where disease has been eradicated in domestic animals. Case Presentation: A 63-year-old diabetic man presented with an 11-year history of painless swelling over his right knee. Magnetic resonance imaging (MRI) showed a large, multiloculated cyst overlying the knee joint. The patient underwent bursectomy which revealed caseous necrosis. Operative samples cultured Brucella abortus. The patient was treated with a combination of surgery and antimicrobials (doxycycline, rifampicin and gentamicin). His only risk factor for acquiring Brucella was drinking unpasteurized milk during childhood. Fifty eight cases of Brucella bursitis have been described in the English-language medical literature. Half have involved the prepatellar bursa. Only one case, from Australia, occurred in a country that has eradicated brucellosis in domestic animals. Although symptoms are often prolonged, local features of inflammation are usually absent. Diagnosis is primarily by bursal fluid culture. Treatment involves antimicrobials with or without aspiration or excision of the bursa. As the diagnosis was unexpected, several laboratory workers were exposed to the Brucella isolate before its identification. Follow up according to UK guidelines revealed no cases of occupationally acquired infection. Conclusion: Bursitis is an unusual manifestation of brucellosis. It is extremely rare outside countries where the infection is endemic, but the chronicity of symptoms and increase in global travel mean that patients with the condition may present in non-endemic settings. Clinicians should therefore consider the diagnosis in cases of unexplained chronic bursitis.
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- 2015
13. Early diagnosis of cardiac implantable electronic device generator pocket infection using F-18-FDG-PET/CT
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Ahmed, FZ, James, J, Cunnington, C, Motwani, M, Fullwood, C, Hooper, J, Burns, P, Qamruddin, A, Al-Bahrani, G, Armstrong, I, Tout, D, Clarke, B, Sandoe, JAT, Arumugam, P, Mamas, MA, and Zaidi, AM
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Aims: To examine the utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the early diagnosis of cardiac implantable electronic device (CIED) generator pocket infection. Methods and results: A total of 86 patients with CIEDs were evaluated with 18F-FDG PET/CT imaging: 46 with suspected generator pocket infection and 40 without any history of infection. 18F-FDG activity in the region of the generator pocket was expressed as a semi-quantitative ratio (SQR)—defined as the maximum count rate around the CIED divided by the mean count rate between normal right and left lung parenchyma. All patients underwent standard clinical management, independent of the PET/CT result. Patients with suspected generator pocket infection that required CIED extraction (n = 32) had significantly higher 18F-FDG activity compared with those that did not (n = 14), and compared with controls (n = 40) [SQR: 4.80 (3.18–7.05) vs. 1.40 (0.88–1.73) vs. 1.10 (0.98–1.40), respectively; P < 0.001]. On receiver operator characteristic analysis, SQR had a high diagnostic accuracy (area under curve = 0.98) for the early identification of patients with confirmed infection (i.e. those ultimately needing extraction)—with an optimal SQR cut-off value of >2.0 (sensitivity = 97%; specificity = 98%). Conclusion: This study highlights the potential benefits of evaluating patients with suspected CIED generator pocket infection using 18F-FDG PET/CT. In this study, 18F-FDG PET/CT had a high diagnostic accuracy in the early diagnosis of CIED generator pocket infection, even where initial clinical signs were underwhelming.
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- 2015
14. Paediatric neck abscesses: microbiology and management.
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Rustom IK, Sandoe JAT, and Makura ZGG
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- 2008
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15. In situ diagnosis of intravascular catheter-related bloodstream infection: a comparison of quantitative culture, differential time to positivity, and endoluminal brushing.
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Catton JA, Dobbins BM, Kite P, Wood JM, Eastwood K, Sugden S, Sandoe JAT, Burke D, McMahon MJ, Wilcox MH, Catton, James A, Dobbins, Brian M, Kite, Peter, Wood, Jonathan M, Eastwood, Kerrie, Sugden, Sarah, Sandoe, Jonathon A T, Burke, Dermot, McMahon, Michael J, and Wilcox, Mark H
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- 2005
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16. Surgical techniques and outcomes in patients with intra-cardiac abscesses complicating infective endocarditis
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Straw, S, Baig, MW, Mishra, V, Gillott, R, Witte, KK, Van Doorn, C, Ferrara, A, Javangula, K, and Sandoe, JAT
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Cardiology and Cardiovascular Medicine - Abstract
BackgroundAn intra-cardiac abscess is a serious complication of both native (NV-IE) and prosthetic valve infective endocarditis (PV-IE). Despite being an accepted indication for surgery, controversies remain regarding the optimal timing and type of operation. We aimed to report the outcomes of patients managed for intra-cardiac abscesses over more than a decade.MethodsPatients aged ≥18 years managed for intra-cardiac abscess between 1 January 2005 and 31 December 2017 were identified from a prospectively collected IE database. The primary outcome was 30-day mortality in operated patients and secondary outcomes were freedom from re-infection, re-operation and long-term mortality comparing those patients with aortic root abscess who underwent aortic valve replacement (AVR) and those who received aortic root replacement (ARR).ResultsFifty-nine patients developed an intra-cardiac abscess, and their median age was 55 (43–71) years; among them, 44 (75%) were men, and 10 (17%) were persons who injected drugs. Infection with beta-haemolytic streptococci was associated with NV-IE (p= 0.009) and coagulase-negative staphylococci with PV-IE (p= 0.005). Forty-four (75%) underwent an operation, and among those with aortic root abscess, 27 underwent AVR and 12 ARR. Thirty-day mortality was associated with infection withS. aureus(p= 0.006) but not the type or timing of the operation. Survival in operated patients was 66% at 1 year and 59% at 5 years. In operated patients, none had a relapse, although six developed late recurrence. Freedom from infection, re-operation and long-term mortality were similar in patients undergoing AVR compared to ARR.ConclusionPatients diagnosed with intra-cardiac abscess who were not operated on had very poor survival. In those who underwent an operation, either by AVR or ARR based upon patient factors, imaging and intra-operative findings outcomes were similar.
17. A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19.
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Sandoe JAT, Grozeva D, Albur M, Bond SE, Brookes-Howell L, Dark P, Euden J, Hamilton R, Hellyer TP, Henley J, Hopkins S, Howard P, Howdon D, Knox-Macaulay C, Llewelyn MJ, Maboshe W, McCullagh IJ, Ogden M, Parsons HK, Partridge DG, Powell N, Prestwich G, Shaw D, Shinkins B, Szakmany T, Thomas-Jones E, Todd S, West RM, Carrol ED, and Pallmann P
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Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK., Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups., Methods: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020., Results: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections., Conclusions: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility., Study Registration Number: ISRCTN66682918., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
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- 2024
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18. Factors influencing implementation and adoption of direct oral penicillin challenge for allergy delabelling: a qualitative evaluation.
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Jani YH, Williams I, McErlean M, Bhogal R, Ng BY, Kildonaviciute K, Balaji A, Daniels R, Dunsmure L, Hullur C, Jones N, Misbah S, Pollard R, Powell N, Sandoe JAT, Thomas C, Warner A, West RM, Savic L, and Thirumala Krishna M
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- Humans, Female, Male, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents adverse effects, Adult, Middle Aged, Interviews as Topic methods, Administration, Oral, Penicillins adverse effects, Penicillins administration & dosage, Qualitative Research, Drug Hypersensitivity psychology, Focus Groups methods
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Background: Over 95% of penicillin allergy labels are inaccurate and may be addressed in low-risk patients using direct oral penicillin challenge (DPC). This study explored the behaviour, attitudes and acceptability of patients, healthcare professionals (HCPs) and managers of using DPC in low-risk patients., Methods: Mixed-method, investigation involving patient interviews and staff focus groups at three NHS acute hospitals. Transcripts were coded using inductive and deductive thematic analysis informed by the Theoretical Domains Framework., Findings: Analysis of 43 patient interviews and three focus groups (28 HCPs: clinicians and managers) highlighted themes of 'knowledge', 'beliefs about capabilities and consequences', 'environmental context', 'resources', 'social influences', 'professional role and identity', 'behavioural regulation and reinforcement' and a cross-cutting theme of digital systems. Overall, study participants supported the DPC intervention. Patients expressed reassurance about being in a monitored, hospital setting. HCPs acknowledged the need for robust governance structures for ensuring clarity of roles and responsibilities and confidence., Conclusion: There were high levels of acceptability among patients and HCPs. HCPs recognised the importance of DPC. Complexities of penicillin allergy (de)labelling were highlighted, and issues of knowledge, risk, governance and workforce were identified as key determinants. These should be considered in future planning and adoption strategies for DPC., Competing Interests: Competing interests: MTK received research funds from NIHR RfPB, MRC CiC, GCRF, FSA and University of Birmingham outside this work. His department at UHB received educational grants for PracticAllergy Course from ALK Abello, Allergy Therapeutics, MEDA, Thermo Fisher Scientific and other pharmaceutical companies over the years. He is Chair of Equality, Diversity and Inclusion working group of BSACI, co-author for BSACI guidelines on penicillin allergy and an associate editor for Clinical Experimental Allergy. RD delivered paid consultancy services to Baxter medical. He has a salaried position as chief executive of UK Sepsis Trust. RB received funding or honoraria for conference attendance, Advisory boards, lectures and training from Pfizer and Menarini. Senior Editor for JAC-AMR (BSAC journal). NP is a NIHR/ HEE CDRF studying non-allergist penicillin allergy de-labelling in secondary care (Clinical Doctoral Research Fellowship). He is co-lead on the BSAC MOOC on non-allergist penicillin allergy de-labelling (British Society Antimicrobial Chemotherapy Massive Open Online Community). SAM is National Clinical Director for the Blood and Infection Programme of Care, NHS England. JATS has research funding from the NIHR and Wellcome Trust in relation to penicillin allergy. He is a member of the British Society for Allergy and Clinical Immunology allergy working party. He is co-lead on the BSAC MOOC on non-allergist penicillin allergy de-labelling (British Society Antimicrobial Chemotherapy Massive Open Online Community) and a BSAC council member., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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19. The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.
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Webb EJD, Howdon D, Bestwick R, King N, Sandoe JAT, Euden J, Grozeva D, West R, Howard P, Powell N, Albur M, Bond S, Brookes-Howell L, Dark P, Hellyer T, Llewelyn M, McCullagh IJ, Ogden M, Pallmann P, Parsons H, Partridge D, Shaw D, Szakmany T, Todd S, Thomas-Jones E, Carrol ED, and Shinkins B
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- Humans, Male, Retrospective Studies, Female, Middle Aged, Aged, Hospitalization economics, SARS-CoV-2, Quality-Adjusted Life Years, Adult, COVID-19 Drug Treatment, United Kingdom, Bacterial Infections drug therapy, Bacterial Infections economics, Procalcitonin blood, Cost-Benefit Analysis, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents economics, COVID-19
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Background: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK., Objectives: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme., Methods: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping., Results: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon., Conclusions: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
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- 2024
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20. Introducing the UK Antimicrobial Registry (UKAR) study: providing real world data on new antimicrobials to support antimicrobial stewardship and tackle antimicrobial resistance.
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Sneddon J, Macfarlane GJ, Jones GT, Moir L, Parr R, Jenkins D, Guise T, Sandoe JAT, and Seaton RA
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The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
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- 2024
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21. A multicentre observational study to investigate feasibility of a direct oral penicillin challenge in de-labelling 'low risk' patients with penicillin allergy by non-allergy healthcare professionals (SPACE study): Implications for healthcare systems.
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Krishna MT, Bhogal R, Ng BY, Kildonaviciute K, Jani YH, Williams I, Sandoe JAT, Pollard R, Jones N, Dunsmure L, Powell N, Hullur C, Balaji A, Moriarty C, Jackson B, Warner A, Daniels R, West R, Thomas C, Misbah SA, and Savic L
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- Humans, Penicillins adverse effects, Anti-Bacterial Agents adverse effects, Feasibility Studies, Skin Tests, Delivery of Health Care, Drug Hypersensitivity diagnosis, Hypersensitivity
- Abstract
Objective: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling., Methods: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC., Results: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors., Interpretation: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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22. Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial.
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Armitage KF, Porter CE, Ahmed S, Cook J, Boards J, Bongard E, Butler CC, Corfield K, Davoudianfar M, Galal U, Howard P, Mujica-Mota R, Saman R, Santillo M, Savic S, Shinkins B, Tonkin-Crine S, Wanat M, West RM, Yu LM, Pavitt S, and Sandoe JAT
- Subjects
- Adult, Humans, Alabama, Anti-Bacterial Agents adverse effects, Drug Resistance, Bacterial, Multicenter Studies as Topic, Penicillins adverse effects, Pilot Projects, Randomized Controlled Trials as Topic, State Medicine, Pragmatic Clinical Trials as Topic, Drug Hypersensitivity, Hypersensitivity
- Abstract
Introduction: Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing., Methods and Analysis: The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation., Ethics and Dissemination: This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal., Trial Registration: ISRCTN20579216., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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23. Expert consensus recommendations for the provision of infective endocarditis services: updated guidance from the Joint British Societies.
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Sandoe JAT, Ahmed F, Arumugam P, Guleri A, Horner C, Howard P, Perry J, Prendergast BD, Schwiebert R, Steeds RP, Watkin R, Wendler O, and Chambers JB
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- Humans, Consensus, United Kingdom, Ireland, Endocarditis, Bacterial diagnosis, Endocarditis therapy, Endocarditis drug therapy
- Abstract
Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association., Competing Interests: Competing interests: The British Society for Antimicrobial Chemotherapy provided funds for literature search, administrative support and meeting space. JATS (JS) received research funding from the National Institute for Health Research, the Medical Research Council, Welcome Trust, Engineering and Physical Sciences Council, and Jon Moulton Charity Trust. JS received consulting fees from Tillotts Pharma and Medtron. BDP and JBC are on the Editorial Board for BMJ Heart. BDP received consulting fees from Anteris and Microport, honoraria from Medtronic, Abbott, Edwards Lifesciences and Anteris and is on the data safety monitoring committee of Colibri. He is a board member of PCR and has received writing fees from Edwards Lifesciences., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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24. Procalcitonin Evaluation of Antibiotic Use in COVID-19 Hospitalised Patients (PEACH): Protocol for a Retrospective Observational Study.
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Euden J, Pallmann P, Grozeva D, Albur M, Bond SE, Brookes-Howell L, Dark P, Hellyer T, Hopkins S, Howard P, Llewelyn MJ, Maboshe W, McCullagh IJ, Ogden M, Parsons H, Partridge D, Powell N, Shaw D, Shinkins B, Szakmany T, Todd S, Thomas-Jones E, West RM, Carrol ED, and Sandoe JAT
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is a viral illness, many patients admitted to hospital are prescribed antibiotics, based on concerns that COVID-19 patients may experience secondary bacterial infections, and the assumption that they may respond well to antibiotic therapy. This has led to an increase in antibiotic use for some hospitalised patients at a time when accumulating antibiotic resistance is a major global threat to health. Procalcitonin (PCT) is an inflammatory marker measured in blood samples and widely recommended to help diagnose bacterial infections and guide antibiotic treatment. The PEACH study will compare patient outcomes from English and Welsh hospitals that used PCT testing during the first wave of the COVID-19 pandemic with those from hospitals not using PCT. It will help to determine whether, and how, PCT testing should be used in the NHS in future waves of COVID-19 to protect patients from antibiotic overuse. PEACH is a retrospective observational cohort study using patient-level clinical data from acute hospital Trusts and Health Boards in England and Wales. The primary objective is to measure the difference in antibiotic use between COVID-19 patients who did or did not have PCT testing at the time of diagnosis. Secondary objectives include measuring differences in length of stay, mortality, intensive care unit admission, and resistant bacterial infections between these groups.
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- 2022
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25. Impact of introducing procalcitonin testing on antibiotic usage in acute NHS hospitals during the first wave of COVID-19 in the UK: a controlled interrupted time series analysis of organization-level data-authors' response.
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Llewelyn MJ, West RM, Carrol ED, Pallmann P, and Sandoe JAT
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- Humans, Procalcitonin, Interrupted Time Series Analysis, State Medicine, Hospitals, United Kingdom, Anti-Bacterial Agents therapeutic use, COVID-19 Drug Treatment
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- 2022
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26. A Systematic Review of the Effect of Therapeutic Drug Monitoring on Patient Health Outcomes during Treatment with Carbapenems.
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Luxton TN, King N, Wälti C, Jeuken LJC, and Sandoe JAT
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Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration. Bias in the studies was assessed with risk of bias analysis tools. Study characteristics and outcomes were tabulated and a narrative synthesis was performed. In total, 2 randomised controlled trials (RCTs), 17 non-randomised studies, and 19 clinical case studies were included. Significant variation in TDM practice was seen; consequently, a meta-analysis was unsuitable. Few studies assessed impacts on AMR. No significant improvement on health outcomes and no detrimental effects of carbapenem TDM were observed. Five cohort studies showed significant associations between achieving target concentrations and clinical success, including suppression of resistance. Studies in this review showed no obvious improvement in clinical outcomes when TDM is implemented. Optimisation and standardisation of carbapenem TDM practice are needed to improve intervention success and enable study synthesis. Further suitably powered studies of standardised TDM are required to assess the impact of TMD on clinical outcomes and AMR.
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- 2022
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27. Diagnostic accuracy of splinter haemorrhages in patients referred for suspected infective endocarditis.
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Schwiebert R, Baig W, Wu J, and Sandoe JAT
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Objective: Splinter haemorrhages are an examination finding that has classically been associated with infective endocarditis (IE), but are not included in current diagnostic algorithms. Splinter haemorrhages have not been evaluated as a diagnostic tool using modern definitions of IE. We determined their sensitivity and specificity in patients with suspected IE and investigated their inclusion in the Duke criteria., Methods: This is a retrospective diagnostic accuracy study using data from 1119 patients with suspected IE referred to the IE service. Patients were categorised according to the Duke criteria, the current diagnostic gold standard, into Duke 'rejected', 'possible' or 'definite' groups. Definite cases (n=451) served as the true positives and rejected cases (n=486) as the true negatives against which splinter haemorrhages were compared. Duke possible cases (n=182) were used the assess the clinical impact of adding splinter haemorrhages to the Duke criteria., Results: In clinically suspected cases of IE and using the Duke criteria as the gold standard comparator, splinter haemorrhages had a sensitivity of 26% (95% CI 22 to 31) (119 out of 451) and a specificity of 83% (95% CI 79 to 86) (403 out of 486). Inclusion of splinter haemorrhages as a minor vascular phenomenon in the Duke criteria would result in a reclassification of 12% of cases from Duke rejected to possible and 13% from Duke possible to definite., Conclusion: Splinter haemorrhages are an insensitive tool in the diagnosis of IE, but their high specificity indicates they do have clinical value in patients with suspected infection. Their inclusion in the Duke criteria as a minor vascular criterion reduces diagnostic uncertainty for some Duke possible cases, while increasing it for a similar proportion of Duke rejected cases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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28. Surgical Techniques and Outcomes in Patients With Intra-Cardiac Abscesses Complicating Infective Endocarditis.
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Straw S, Baig MW, Mishra V, Gillott R, Witte KK, Van Doorn C, Ferrara A, Javangula K, and Sandoe JAT
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Background: An intra-cardiac abscess is a serious complication of both native (NV-IE) and prosthetic valve infective endocarditis (PV-IE). Despite being an accepted indication for surgery, controversies remain regarding the optimal timing and type of operation. We aimed to report the outcomes of patients managed for intra-cardiac abscesses over more than a decade., Methods: Patients aged ≥18 years managed for intra-cardiac abscess between 1 January 2005 and 31 December 2017 were identified from a prospectively collected IE database. The primary outcome was 30-day mortality in operated patients and secondary outcomes were freedom from re-infection, re-operation and long-term mortality comparing those patients with aortic root abscess who underwent aortic valve replacement (AVR) and those who received aortic root replacement (ARR)., Results: Fifty-nine patients developed an intra-cardiac abscess, and their median age was 55 (43-71) years; among them, 44 (75%) were men, and 10 (17%) were persons who injected drugs. Infection with beta-haemolytic streptococci was associated with NV-IE ( p = 0.009) and coagulase-negative staphylococci with PV-IE ( p = 0.005). Forty-four (75%) underwent an operation, and among those with aortic root abscess, 27 underwent AVR and 12 ARR. Thirty-day mortality was associated with infection with S. aureus ( p = 0.006) but not the type or timing of the operation. Survival in operated patients was 66% at 1 year and 59% at 5 years. In operated patients, none had a relapse, although six developed late recurrence. Freedom from infection, re-operation and long-term mortality were similar in patients undergoing AVR compared to ARR., Conclusion: Patients diagnosed with intra-cardiac abscess who were not operated on had very poor survival. In those who underwent an operation, either by AVR or ARR based upon patient factors, imaging and intra-operative findings outcomes were similar., Competing Interests: JS has participated in research funded by Pfizer and Merck Sharpe and Dohme. KW has received speakers' fees and honoraria from Medtronic, Cardiac Dimensions, Novartis, Abbott, BMS, Pfizer, and Bayer has received an unconditional research grant from Medtronic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Straw, Baig, Mishra, Gillott, Witte, Van Doorn, Ferrara, Javangula and Sandoe.)
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- 2022
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29. Risk of infective endocarditis after surgical and transcatheter aortic valve replacement.
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Cahill TJ, Raby J, Jewell PD, Brennan PF, Banning AP, Byrne J, Kharbanda RK, MacCarthy PA, Thornhill MH, Sandoe JAT, Spence MS, Ludman P, Hildick-Smith DJR, Redwood SR, and Prendergast BD
- Subjects
- Aortic Valve surgery, Humans, Male, Risk Factors, Treatment Outcome, Aortic Valve Stenosis complications, Endocarditis epidemiology, Endocarditis etiology, Endocarditis surgery, Endocarditis, Bacterial surgery, Heart Valve Prosthesis adverse effects, Heart Valve Prosthesis Implantation adverse effects, Transcatheter Aortic Valve Replacement adverse effects
- Abstract
Objective: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI)., Methods: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee., Results: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis., Conclusions: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI., Competing Interests: Competing interests: BDP has received unrestricted education and research grants from Edwards Lifesciences and speaker fees from Edwards Lifesciences. SRR has served as a proctor for and received speaker fees from Edwards Lifesciences, and has served on the advisory board for Medtronic. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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30. Protein-conjugated microbubbles for the selective targeting of S. aureus biofilms.
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Caudwell JA, Tinkler JM, Johnson BRG, McDowall KJ, Alsulaimani F, Tiede C, Tomlinson DC, Freear S, Turnbull WB, Evans SD, and Sandoe JAT
- Abstract
Staphylococcus aureus ( S. aureus ) is an important human pathogen and a common cause of bloodstream infection. The ability of S. aureus to form biofilms, particularly on medical devices, makes treatment difficult, as does its tendency to spread within the body and cause secondary foci of infection. Prolonged courses of intravenous antimicrobial treatment are usually required for serious S. aureus infections. This work investigates the in vitro attachment of microbubbles to S. aureus biofilms via a novel Affimer protein, AClfA1, which targets the clumping factor A (ClfA) virulence factor - a cell-wall anchored protein associated with surface attachment. Microbubbles (MBs) are micron-sized gas-filled bubbles encapsulated by a lipid, polymer, or protein monolayer or other surfactant-based material. Affimers are small (∼12 kDa) heat-stable binding proteins developed as replacements for antibodies. The binding kinetics of AClfA1 against S. aureus ClfA showed strong binding affinity (K
D = 62 ± 3 nM). AClfA1 was then shown to bind S. aureus biofilms under flow conditions both as a free ligand and when bound to microparticles (polymer beads or microbubbles). Microbubbles functionalized with AClfA1 demonstrated an 8-fold increase in binding compared to microbubbles functionalized with an identical Affimer scaffold but lacking the recognition groups. Bound MBs were able to withstand flow rates of 250 μL/min. Finally, ultrasound was applied to burst the biofilm bound MBs to determine whether this would lead to biofilm biomass loss or cell death. Application of a 2.25 MHz ultrasound profile (with a peak negative pressure of 0.8 MPa and consisting of a 22-cycle sine wave, at a pulse repetition rate of 10 kHz) for 2 s to a biofilm decorated with targeted MBs, led to a 25% increase in biomass loss and a concomitant 8% increase in dead cell count. The results of this work show that Affimers can be developed to target S. aureus biofilms and that such Affimers can be attached to contrast agents such as microbubbles or polymer beads and offer potential, with some optimization, for drug-free biofilm treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Published by Elsevier B.V.)- Published
- 2022
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31. Chiral nematic liquid crystal droplets as a basis for sensor systems.
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Paterson DA, Du X, Bao P, Parry AA, Peyman SA, Sandoe JAT, Evans SD, Luo D, Bushby RJ, Jones JC, and Gleeson HF
- Abstract
For a series of phospholipid coated calamitic nematic liquid crystal droplets (5CB, 6CB, 7CB, E7 and MLC7023) of diameter ∼18 μm, the addition of chiral dopant leaves the sign of surface anchoring unchanged. Herein we report that for these chiral nematic droplets an analyte induced transition from a Frank-Pryce structure (with planar anchoring) to a nested-cup structure (with perpendicular anchoring) is accompanied by changes in the intensity of reflected light. We propose this system as both a general scheme for understanding director fields in chiral nematic liquid crystal droplets with perpendicular anchoring and as an ideal candidate to be utilised as the basis for developing cheap, single use LC-based sensor devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
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- 2022
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32. The impact of penicillin allergy de-labelling on the WHO AWaRe antibiotic categories: a retrospective cohort study.
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Powell N, West R, and Sandoe JAT
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- Humans, Penicillins adverse effects, Retrospective Studies, World Health Organization, Anti-Bacterial Agents adverse effects, Drug Hypersensitivity drug therapy, Drug Hypersensitivity epidemiology
- Abstract
Background: The WHO's AWaRe classification categorizes antibiotics into three stewardship groups: Access, Watch and Reserve. The Access group includes antibiotics with lower resistance potential than antibiotics in the other two groups. The UK five-year AMR strategy has set targets for reducing non-Access antibiotic use. The majority of penicillins are in the Access group and therefore patients with a penicillin allergy record are likely to receive more non-Access antibiotics. This study aimed to quantify the impact of penicillin allergy records on non-Access antibiotic prescribing and to estimate potential reductions in non-Access antibiotic use through penicillin allergy de-labelling., Methods: Inpatients of a 750-patient-bed UK district general hospital in England prescribed antibiotics between 1
st April 2018 and 31st March 2019 were included. Variables included: age, sex, co-morbidity, infection treated, antibiotic usage, hospital length of stay, penicillin allergy status. Multivariable logistic regression was used to explore the association between patient characteristics and their receipt of antibiotics in the Access and non-Access groups., Results: A total of 67,059 antibiotic prescriptions for 23,356 inpatients were analysed. Penicillin allergy records were present in 14.3% of hospital admissions. Patients with a penicillin allergy record were around four times more likely (odds ratio = 4.7) to receive an antibiotic from the non-Access groups (i.e. Reserve and Watch groups). We estimate de-labelling 50% of hospital inpatients with a penicillin allergy record could reduce non-Access antibiotic use by 5.8% and total antibiotic use by 0.86%., Conclusion: Penicillin allergy records are associated with non-Access antibiotic prescribing. Penicillin allergy de-labelling has potential to reduce non-Access antibiotic use., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)- Published
- 2021
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33. Development and randomized controlled trial of an animated film aimed at reducing behaviours for acquiring antibiotics.
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Wilding S, Kettu V, Thompson W, Howard P, Jeuken LJC, Pownall M, Conner M, and Sandoe JAT
- Abstract
Background: Antimicrobial resistance (AMR) is a global health crisis but reducing antibiotic use can help. Some antibiotic use is driven by patient demand., Objectives: To develop an intervention to discourage antibiotic-seeking behaviour in adults., Methods: Literature reviewed to identify behaviours for acquiring antibiotics among adults in the community. Behaviour change wheel approach was used to select the target behaviour and behaviour change techniques. An intervention in the form of a short animated film was developed and its potential impact evaluated in a randomized, controlled, online questionnaire study., Results: Asking a general medical/dental practitioner for antibiotics was identified as the target behaviour. A short stop-motion animated film was chosen to deliver several behaviour-change techniques. Education and persuasion were delivered around information about the normal microbial flora, its importance for health, the negative effect of antibiotics, and about AMR. 417 UK-based individuals completed the questionnaire; median age 34.5 years, 71% female, 91% white ethnicity. 3.8% of participants viewing the test film intended to ask for antibiotics compared with 7.9% viewing the control film. Test film viewers had significantly higher knowledge scores. At 6 week follow up, knowledge scores remained significantly different, while most attitude and intention scores were not different., Conclusions: Some patients continue to ask for antibiotics. The film increased knowledge and reduced intentions to ask for antibiotics. At 6 weeks, knowledge gains remained but intentions not to ask for antibiotics had waned. Evaluation in the clinical environment, probably at the point of care, is needed to see if antibiotic prescribing can be impacted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
- Published
- 2021
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34. Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians.
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Wanat M, Anthierens S, Butler CC, Savic L, Savic S, Pavitt SH, Sandoe JAT, and Tonkin-Crine S
- Subjects
- Humans, Penicillins adverse effects, Primary Health Care, Qualitative Research, Drug Hypersensitivity diagnosis, Drug Hypersensitivity therapy, Physicians, Primary Care
- Abstract
Background: Six percent of patients are allergic to penicillin according to their medical records. While this designation protects a small number of truly allergic patients from serious reactions, those who are incorrectly labelled may be denied access to recommended first line treatment for many infections. Removal of incorrect penicillin allergy may have positive health consequences for the individual and the general population. We aimed to explore primary care physicians' (PCPs) and patients' views and understanding of penicillin allergy with a focus on clinical management of infections in the face of a penicillin allergy record., Methods: We conducted an interview study with 31 patients with a penicillin allergy record, and 19 PCPs in the North of England. Data were analysed thematically., Results: Patients made sense of their allergy status by considering the timing and severity of symptoms. Diagnosis of penicillin allergy was reported to be 'imperfect' with PCPs relying on patient reports and incomplete medical records. PCPs and patients often suspected that an allergy record was incorrect, but PCPs were reluctant to change records. PCPs had limited knowledge of allergy services. PCPs often prescribed alternative antibiotics which were easy to identify. Both patients and PCPs differed in the extent to which they were aware of the negative consequences of incorrect penicillin allergy records, their relevance and importance to their lives, and management of penicillin allergy., Conclusions: PCPs and patients appear insufficiently aware of potential harms associated with incorrect penicillin allergy records. Some of the problems experienced by PCPs could be reduced by ensuring the details of newly diagnosed reactions to antibiotics are clearly documented. In order for PCPs to overturn more incorrect penicillin records through appropriate use of allergy services, more information and training about these services will be needed.
- Published
- 2021
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35. Use of Procalcitonin during the First Wave of COVID-19 in the Acute NHS Hospitals: A Retrospective Observational Study.
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Powell N, Howard P, Llewelyn MJ, Szakmany T, Albur M, Bond SE, Euden J, Brookes-Howell L, Dark P, Hellyer TP, Hopkins S, McCullagh IJ, Ogden M, Pallmann P, Parsons H, Partridge DG, Shaw DE, Shinkins B, Todd S, Thomas-Jones E, West R, Carrol ED, and Sandoe JAT
- Abstract
A minority of patients presenting to hospital with COVID-19 have bacterial co-infection. Procalcitonin testing may help identify patients for whom antibiotics should be prescribed or withheld. This study describes the use of procalcitonin in English and Welsh hospitals during the first wave of the COVID-19 pandemic. A web-based survey of antimicrobial leads gathered data about the use of procalcitonin testing. Responses were received from 148/151 (98%) eligible hospitals. During the first wave of the COVID-19 pandemic, there was widespread introduction and expansion of PCT use in NHS hospitals. The number of hospitals using PCT in emergency/acute admissions rose from 17 (11%) to 74/146 (50.7%) and use in Intensive Care Units (ICU) increased from 70 (47.6%) to 124/147 (84.4%). This increase happened predominantly in March and April 2020, preceding NICE guidance. Approximately half of hospitals used PCT as a single test to guide decisions to discontinue antibiotics and half used repeated measurements. There was marked variation in the thresholds used for empiric antibiotic cessation and guidance about interpretation of values. Procalcitonin testing has been widely adopted in the NHS during the COVID-19 pandemic in an unevidenced, heterogeneous way and in conflict with relevant NICE guidance. Further research is needed urgently that assesses the impact of this change on antibiotic prescribing and patient safety.
- Published
- 2021
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36. Production of giant unilamellar vesicles and encapsulation of lyotropic nematic liquid crystals.
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Bao P, Paterson DA, Peyman SA, Jones JC, Sandoe JAT, Gleeson HF, Evans SD, and Bushby RJ
- Abstract
We describe a modified microfluidic method for making Giant Unilamellar Vesicles (GUVs) via water/octanol-lipid/water double emulsion droplets. At a high enough lipid concentration we show that the de-wetting of the octanol from these droplets occurs spontaneously (off-chip) without the need to use shear to aid the de-wetting process. The resultant mixture of octanol droplets and GUVs can be separated by making use of the buoyancy of the octanol. A simpler microfluidic device and pump system can be employed and, because of the higher flow-rates and much higher rate of formation of the double emulsion droplets (∼1500 s-1 compared to up to ∼75 s-1), it is easier to make larger numbers of GUVs and larger volumes of solution. Because of the potential for using GUVs that incorporate lyotropic nematic liquid crystals in biosensors we have used this method to make GUVs that incorporate the nematic phases of sunset yellow and disodium chromoglycate. However, the phase behaviour of these lyotropic liquid crystals is quite sensitive to concentration and we found that there is an unexpected spread in the concentration of the contents of the GUVs obtained.
- Published
- 2021
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37. Long-term Outcomes Are Poor in Intravenous Drug Users Following Infective Endocarditis, Even After Surgery.
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Straw S, Baig MW, Gillott R, Wu J, Witte KK, O'regan DJ, and Sandoe JAT
- Subjects
- Humans, Retrospective Studies, Drug Users, Endocarditis epidemiology, Endocarditis surgery, Endocarditis, Bacterial, Substance Abuse, Intravenous complications
- Abstract
Background: Previous studies of outcomes in people who inject drugs (PWID) with infective endocarditis (IE) have often been retrospective, have had small sample sizes, and the duration of follow-up has been short and limited to patients who were operated on., Methods: PWID treated for IE between 1 January 2006 and 31 December 2016 were identified from a prospectively collected database. PWID hospitalized with other infections acted as a novel comparison group. Outcomes were all-cause mortality, cause of death, relapse, recurrence, and reoperation., Results: There were 105 episodes of IE in 92 PWID and 112 episodes of other infections in 107 PWID in whom IE was suspected but rejected. Survival at 30 days for the IE group was 85%, and 30-day survival following surgery was 96%. The most common pathogens were Staphylococcus species (60%) and Streptococcus species (30%). The surgical intervention rate was 47%. Survival for the IE group at 1, 3, 5, and 10 years was 74%, 63%, 58%, and 44%, respectively. This was significantly lower compared with the comparator group of other infections in PWID (P = .0002). Mortality was higher in patients who required surgery compared with those who did not (hazard ratio, 1.8 [95% confidence interval, .95-3.3]). The commonest cause of death was infection (66%), usually a further episode of IE (55%)., Conclusions: Although early survival was good, long-term life expectancy was low. This was attributable to ongoing infection risk, rather than other factors known to affect prognosis in PWID. Surgery conferred no long-term survival advantage. More efforts are needed to reduce reinfection risk following an episode of IE in PWID.While early survival for people who inject drugs (PWID) with infective endocarditis is good, long-term survival is poor due to ongoing infection risk. Surgery conferred no long-term survival advantage, so more efforts are needed to reduce reinfection risks for PWID., (© Crown copyright 2019.)
- Published
- 2020
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38. Prosthetic valve endocarditis following transcatheter aortic valve implantation.
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Ali N, Baig W, Wu J, Blackman D, Gillott R, and Sandoe JAT
- Subjects
- Aged, Aged, 80 and over, Decision Support Techniques, Endocarditis diagnosis, Endocarditis mortality, England epidemiology, Female, Humans, Incidence, Male, Prosthesis-Related Infections diagnosis, Prosthesis-Related Infections mortality, Retrospective Studies, Risk Factors, Time Factors, Transcatheter Aortic Valve Replacement instrumentation, Transcatheter Aortic Valve Replacement mortality, Treatment Outcome, Endocarditis epidemiology, Heart Valve Prosthesis adverse effects, Prosthesis-Related Infections epidemiology, Transcatheter Aortic Valve Replacement adverse effects
- Abstract
Aims: The aims were to report the incidence and outcomes of transcatheter aortic valve implantation-infective endocarditis (TAVI-IE) from a high-volume TAVI centre in the United Kingdom, including how incidence varies relative to time from the procedure, and to assess the performance of modified Duke criteria in the diagnosis of TAVI-IE., Methods: The retrospective, cohort study included all patients who underwent TAVI at Leeds Teaching Hospitals Trust during a 10-year period. Outcome measures were the incidence of TAVI-IE, the accuracy of the modified Duke criteria and the mortality rate., Results: A total of 1337 patients were followed up for a median of 2.3 years. Thirteen patients (0.97%) were diagnosed with TAVI-IE, mean age of 81.3 years (SD 5.1 years). Four patients (30.8%) fulfilled modified Duke criteria for definite infective endocarditis. The remaining nine patients (69.2%) fulfilled the modified Duke criteria for possible infective endocarditis. In the majority (7/13; 53.8%) the causative organism was streptococcal. Cumulative incidence of TAVI-IE has risen in line with the number of patients living with TAVI prostheses, and cumulative number of TAVI-years. However, in relation to the number of 100 TAVI-years, the infection rate has remained low and static over the last 6 years. The in-hospital mortality rate was 38.5%, all attributable to TAVI-IE., Conclusion: The incidence of TAVI-IE was 0.97%, with an associated all-cause mortality of 53.8%. The incidence relative to the number of TAVI-years has remained low and static in recent years. The modified Duke criteria have relatively low sensitivity in the diagnosis of TAVI-IE, meaning that a high index of suspicion is required.
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- 2020
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39. Control of Director Fields in Phospholipid-Coated Liquid Crystal Droplets.
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Paterson DA, Bao P, Abou-Saleh RH, Peyman SA, Jones JC, Sandoe JAT, Evans SD, Gleeson HF, and Bushby RJ
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In liquid crystal (LC) droplets, small changes in surface anchoring energy can produce large changes in the director field which result in readily detectable optical effects. This makes them attractive for use as biosensors. Coating LC droplets with a phospholipid monolayer provides a bridge between the hydrophobic world of LCs and the water-based world of biology and makes it possible to incorporate naturally occurring biosensor systems. However, phospholipids promote strong perpendicular (homeotropic) anchoring that can inhibit switching of the director field. We show that the tendency for phospholipid layers to promote perpendicular anchoring can be suppressed by using synthetic phospholipids in which the acyl chains are terminated with bulky tert -butyl or ferrocenyl groups; the larger these end-group(s), the less likely the system is to be perpendicular/radial. Additionally, the droplet director field is found to be dependent on the nature of the LC, particularly its intrinsic surface properties, but not (apparently) on the sign of the dielectric anisotropy, the proximity to the melting/isotropic phase transition, the surface tension (in air), or the values of the Frank elastic constants.
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- 2020
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40. 'Antibiotic footprint' as a communication tool to aid reduction of antibiotic consumption-authors' response.
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Limmathurotsakul D, Sandoe JAT, Barrett DC, Corley M, Hsu LY, Mendelson M, Collignon P, Laxminarayan R, Peacock SJ, and Howard P
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- Anti-Bacterial Agents, Communication
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- 2020
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41. 'Antibiotic footprint' as a communication tool to aid reduction of antibiotic consumption-authors' response.
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Limmathurotsakul D, Sandoe JAT, Barrett DC, Corley M, Hsu LY, Mendelson M, Collignon P, Laxminarayan R, Peacock SJ, and Howard P
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- Anti-Bacterial Agents, Communication
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- 2019
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42. Cross-sectional study of the prevalence, causes and management of hospital-onset diarrhoea.
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Mawer D, Byrne F, Drake S, Brown C, Prescott A, Warne B, Bousfield R, Skittrall JP, Ramsay I, Somasunderam D, Bevan M, Coslett J, Rao J, Stanley P, Kennedy A, Dobson R, Long S, Obisanya T, Esmailji T, Petridou C, Saeed K, Brechany K, Davis-Blue K, O'Horan H, Wake B, Martin J, Featherstone J, Hall C, Allen J, Johnson G, Hornigold C, Amir N, Henderson K, McClements C, Liew I, Deshpande A, Vink E, Trigg D, Guilfoyle J, Scarborough M, Scarborough C, Wong THN, Walker T, Fawcett N, Morris G, Tomlin K, Grix C, O'Cofaigh E, McCaffrey D, Cooper M, Corbett K, French K, Harper S, Hayward C, Reid M, Whatley V, Winfield J, Hoque S, Kelly L, King I, Bradley A, McCullagh B, Hibberd C, Merron M, McCabe C, Horridge S, Taylor J, Koo S, Elsanousi F, Saunders R, Lim F, Bond A, Stone S, Milligan ID, Mack DJF, Nagar A, West RM, Wilcox MH, Kirby A, and Sandoe JAT
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- Aged, Aged, 80 and over, Cross Infection diagnosis, Cross Infection therapy, Cross-Sectional Studies, Diarrhea diagnosis, Diarrhea therapy, England epidemiology, Female, Hospitals, Humans, Male, Prevalence, Prospective Studies, Cross Infection epidemiology, Cross Infection etiology, Diarrhea epidemiology, Diarrhea etiology, Disease Management
- Abstract
Background: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking., Aim: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards., Methods: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively., Findings: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset., Conclusion: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)
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- 2019
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43. 'Caveat emptor': the cautionary tale of endocarditis and the potential pitfalls of clinical coding data-an electronic health records study.
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Fawcett N, Young B, Peto L, Quan TP, Gillott R, Wu J, Middlemass C, Weston S, Crook DW, Peto TEA, Muller-Pebody B, Johnson AP, Walker AS, and Sandoe JAT
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- Databases, Factual, Female, Humans, Incidence, International Classification of Diseases, Retrospective Studies, Clinical Coding standards, Electronic Health Records standards, Endocarditis epidemiology
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Background: Diagnostic codes from electronic health records are widely used to assess patterns of disease. Infective endocarditis is an uncommon but serious infection, with objective diagnostic criteria. Electronic health records have been used to explore the impact of changing guidance on antibiotic prophylaxis for dental procedures on incidence, but limited data on the accuracy of the diagnostic codes exists. Endocarditis was used as a clinically relevant case study to investigate the relationship between clinical cases and diagnostic codes, to understand discrepancies and to improve design of future studies., Methods: Electronic health record data from two UK tertiary care centres were linked with data from a prospectively collected clinical endocarditis service database (Leeds Teaching Hospital) or retrospective clinical audit and microbiology laboratory blood culture results (Oxford University Hospitals Trust). The relationship between diagnostic codes for endocarditis and confirmed clinical cases according to the objective Duke criteria was assessed, and impact on estimations of disease incidence and trends., Results: In Leeds 2006-2016, 738/1681(44%) admissions containing any endocarditis code represented a definite/possible case, whilst 263/1001(24%) definite/possible endocarditis cases had no endocarditis code assigned. In Oxford 2010-2016, 307/552(56%) reviewed endocarditis-coded admissions represented a clinical case. Diagnostic codes used by most endocarditis studies had good positive predictive value (PPV) but low sensitivity (e.g. I33-primary 82% and 43% respectively); one (I38-secondary) had PPV under 6%. Estimating endocarditis incidence using raw admission data overestimated incidence trends twofold. Removing records with non-specific codes, very short stays and readmissions improved predictive ability. Estimating incidence of streptococcal endocarditis using secondary codes also overestimated increases in incidence over time. Reasons for discrepancies included changes in coding behaviour over time, and coding guidance allowing assignment of a code mentioning 'endocarditis' where endocarditis was never mentioned in the clinical notes., Conclusions: Commonly used diagnostic codes in studies of endocarditis had good predictive ability. Other apparently plausible codes were poorly predictive. Use of diagnostic codes without examining sensitivity and predictive ability can give inaccurate estimations of incidence and trends. Similar considerations may apply to other diseases. Health record studies require validation of diagnostic codes and careful data curation to minimise risk of serious errors.
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- 2019
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44. Factors associated with antibiotic prescribing for adults with acute conditions: an umbrella review across primary care and a systematic review focusing on primary dental care.
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Thompson W, Tonkin-Crine S, Pavitt SH, McEachan RRC, Douglas GVA, Aggarwal VR, and Sandoe JAT
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- Acute Disease therapy, Adult, Antimicrobial Stewardship, Clinical Decision-Making, Humans, Systematic Reviews as Topic, Anti-Bacterial Agents administration & dosage, Dental Care statistics & numerical data, Drug Prescriptions statistics & numerical data, Practice Patterns, Physicians' statistics & numerical data, Primary Health Care statistics & numerical data
- Abstract
Introduction: One way to slow the spread of resistant bacteria is by improved stewardship of antibiotics: using them more carefully and reducing the number of prescriptions. With an estimated 7%-10% of antibiotic prescriptions globally originating from dental practices and up to 80% prescribed unnecessarily, dentistry has an important role to play. To support the design of new stewardship interventions through knowledge transfer between contexts, this study aimed to identify factors associated with the decision to prescribe antibiotics to adults presenting with acute conditions across primary care (including dentistry)., Methods: Two reviews were undertaken: an umbrella review across primary healthcare and a systematic review in dentistry. Two authors independently selected and quality assessed the included studies. Factors were identified using an inductive thematic approach and mapped to the Theoretical Domains Framework (TDF). Comparisons between dental and other settings were explored. Registration number: PROSPERO_CRD42016037174., Results: Searches identified 689 publications across primary care and 432 across dental care. Included studies (nine and seven, respectively) were assessed as of variable quality. They covered 46 countries, of which 12 were low and middle-income countries (LMICs). Across the two reviews, 30 factors were identified, with 'patient/condition characteristics', 'patient influence' and 'guidelines & information' the most frequent. Two factors were unique to dental studies: 'procedure possible' and 'treatment skills'. No factor related only to LMICs., Conclusions: A comprehensive list of factors associated with antibiotic prescribing to adults with acute conditions in primary care settings around the world has been collated and should assist theory-informed design of new context-specific stewardship interventions., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
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- 2019
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45. 'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.
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West RM, Smith CJ, Pavitt SH, Butler CC, Howard P, Bates C, Savic S, Wright JM, Hewison J, and Sandoe JAT
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- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Drug Prescriptions statistics & numerical data, Electronic Health Records, England epidemiology, Female, Humans, Male, Middle Aged, Odds Ratio, Outcome Assessment, Health Care, Practice Patterns, Physicians', Prevalence, Retrospective Studies, Young Adult, Anti-Bacterial Agents adverse effects, Drug Hypersensitivity epidemiology, Drug Hypersensitivity immunology, Penicillins adverse effects
- Abstract
Background: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging., Objectives: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care., Methods: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection., Results: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR) = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records., Conclusions: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2019
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46. Penicillin allergy de-labelling ahead of elective surgery: feasibility and barriers.
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Savic L, Gurr L, Kaura V, Toolan J, Sandoe JAT, Hopkins PM, and Savic S
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- Feasibility Studies, Humans, United Kingdom, Amoxicillin administration & dosage, Anti-Bacterial Agents administration & dosage, Drug Hypersensitivity diagnosis, Elective Surgical Procedures, Penicillins administration & dosage, Preoperative Care methods
- Abstract
Background: Around 10-15% of the in-patient population carry unsubstantiated 'penicillin allergy' labels, the majority incorrect when tested. These labels are associated with harm from use of broad-spectrum non-penicillin antibiotics. Current testing guidelines incorporate both skin and challenge tests; this is prohibitively expensive and time-consuming to deliver on a large scale. We aimed to establish the feasibility of a rapid access de-labelling pathway for surgical patients, using direct oral challenge., Methods: 'Penicillin allergic' patients, recruited from a surgical pre-assessment clinic, were risk-stratified using a screening questionnaire. Patients at low risk of true, immunoglobulin E (IgE)-mediated allergy were offered direct oral challenge using incremental amoxicillin to a total dose of 500 mg. A 3-day course was completed at home. De-labelled patients were followed up to determine antibiotic use in surgery, and attitudes towards de-labelling were explored., Results: Of 219 patients screened, 74 were eligible for inclusion and offered testing. We subsequently tested 56 patients; 55 were de-labelled. None had a serious reaction to the supervised challenge, or thereafter. On follow-up, 17 of 19 patients received appropriate antimicrobial prophylaxis during surgery. Only three of 33 de-labelled patients would have been happy for the label to be removed without prior specialist testing., Conclusion: Rapid access de-labelling, using direct oral challenge in appropriately risk-stratified patients, can be incorporated into the existing surgical care pathway. This provides immediate and potential long-term benefit for patients. Interest in testing is high among patients, and clinicians appear to follow clinic recommendations. Patients are unlikely to accept removal of their allergy label on the basis of history alone., Clinical Trial Registration: ClinicalTrials.gov: AN17/92982., (Copyright © 2018 British Journal of Anaesthesia. All rights reserved.)
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- 2019
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47. Patient and Primary Care Physician Perceptions of Penicillin Allergy Testing and Subsequent Use of Penicillin-Containing Antibiotics: A Qualitative Study.
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Wanat M, Anthierens S, Butler CC, Savic L, Savic S, Pavitt SH, Sandoe JAT, and Tonkin-Crine S
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- Adult, Aged, Female, Humans, Male, Middle Aged, Perception, Qualitative Research, Skin Tests, Young Adult, Anti-Bacterial Agents adverse effects, Attitude of Health Personnel, Attitude to Health, Drug Hypersensitivity diagnosis, Penicillins adverse effects, Physicians, Primary Care psychology
- Abstract
Background: Removal of an inaccurate penicillin allergy record following testing allows patients to access first-line treatment for infections, and reduce the use of broad-spectrum antibiotics, which contribute to antibiotic resistance. However, it is seldom undertaken., Objectives: To identify clinicians' working in primary care and patients' views on barriers and enablers for penicillin allergy testing and subsequent antibiotic use., Methods: Fifty interviews with patients and clinicians, including 31 patients with a record of penicillin allergy, 16 with experience of testing, and 19 clinicians. Interviews were analyzed thematically., Results: Patients were often unaware of the benefits of penicillin allergy testing and only those patients who had experienced negative consequences of having a penicillin allergy label were motivated to get tested. Clinicians were reluctant to change patient records on the basis of their clinical judgment alone but had limited experience of referring patients with suspected penicillin allergy and were often uncertain about referral criteria and what the testing involved. Clinicians felt that allergy testing could be beneficial and patients who had attended testing reported benefits of the test. Clinicians expressed uncertainty related to whose responsibility it was to make sure that the patient understood allergy test results., Conclusions: Clinicians would benefit from information about penicillin allergy testing to be able to use these services appropriately, and to discuss referral with patients. Patients might be more motivated to seek testing if they were more informed regarding its benefits. Good communication between primary and secondary care would facilitate the updating of medical records, and promote better patient education., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
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- 2019
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48. Impact of the duration of antibiotic therapy on relapse and survival following surgery for active infective endocarditis.
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Rao VP, Wu J, Gillott R, Baig MW, Kaul P, and Sandoe JAT
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- Adult, Aged, Anti-Bacterial Agents administration & dosage, Cardiac Surgical Procedures adverse effects, Cardiac Surgical Procedures methods, Cardiac Surgical Procedures mortality, Endocarditis drug therapy, Endocarditis mortality, Female, Humans, Male, Middle Aged, Postoperative Care methods, Recurrence, Reoperation mortality, Reoperation statistics & numerical data, Retrospective Studies, Secondary Prevention methods, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Endocarditis surgery
- Abstract
Objectives: Surgery is often required for acute infective endocarditis (IE) to repair or replace damaged heart valves. Traditionally, long courses of antibiotic treatment have been prescribed after surgery for active IE for fear of infecting newly implanted/repaired valves, but the need for this, in the present era of enhanced antimicrobial stewardship, has been questioned. In our institution, the choice and duration of antimicrobial therapy is tailored to individual patients by a multidisciplinary team with an interest in IE. The influence of the duration of postoperative antibiotic therapy on outcomes was studied in patients requiring surgery prior to the completion of a planned course of antibiotic therapy., Methods: This was a retrospective observational study on patients with acute IE requiring surgery between January 2004 and December 2015. The primary outcome was relapse. Secondary outcomes were early reoperation and 1-year mortality., Results: In total, 182 IE episodes were included in the final analysis. The median duration of postoperative antibiotic therapy was 23.5 days (interquartile range 12-40 days) and decreased significantly during the period of study (P < 0.001). There were 2 relapses (1.1%) and 18 (9.9%) postoperative deaths within 1 year. Nine (5%) patients underwent early reoperation. The duration of postoperative antibiotic therapy did not affect either the primary or the secondary outcomes., Conclusions: This work supports previous findings that selected patients who require surgery during active IE can be safely given shorter courses of postoperative antibiotics without an impact on relapse of infection or survival., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
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- 2019
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49. Opportunities for antimicrobial stewardship in patients with acute bacterial skin and skin structure infections who are unsuitable for beta-lactam antibiotics: a multicenter prospective observational study.
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Sandoe JAT, Saeed K, Guleri A, Hand KS, Dillon R, Allen M, Mayes A, Glen F, and Gonzalez-Ruiz A
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Purpose: The objective of this prospective, observational study was to describe the treatment, severity assessment and healthcare resources required for management of patients with acute bacterial skin and skin structure infections who were unsuitable for beta-lactam antibiotic treatments., Methods: Patients were enrolled across five secondary care National Health Service hospitals. Eligible patients had a diagnosis of acute bacterial skin and skin structure infection and were considered unsuitable for beta-lactam antibiotics (e.g. confirmed/suspected methicillin-resistant Staphylococcus aureus , beta-lactam allergy). Data regarding diagnosis, severity of the infection, antibiotic treatment and patient management were collected., Results: 145 patients with acute bacterial skin and skin structure infection were included; 79% ( n = 115) patients received greater than two antibiotic regimens; median length of the first antibiotic regimen was 2 days (interquartile range of 1-5); median time to switch from intravenous to oral antibiotics was 4 days (interquartile range of 3-8, n = 72/107); 25% ( n = 10/40) patients with Eron class 1 infection had systemic inflammatory response syndrome, suggesting they were misclassified. A higher proportion of patients with systemic inflammatory response syndrome received treatment in an inpatient setting, and their length of stay was prolonged in comparison with patients without systemic inflammatory response syndrome., Conclusion: There exists an urgent need for more focused antimicrobial stewardship strategies and tools for standardised clinical assessment of acute bacterial skin and skin structure infection severity in patients who are unsuitable for beta-lactam antibiotics. This will lead to optimised antimicrobial treatment strategies and ensure effective healthcare resource utilisation., Competing Interests: Conflict of interest statement: The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: J.A.T.S. was MSD advisory board member in 2015, A.G.-R. was MSD advisory board member during 2015–2016. R.D., M.A. and A.M. are employees of MSD.
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- 2019
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50. Oral versus Intravenous Antibiotics for Bone and Joint Infection.
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Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, Lipsky BA, Hughes HC, Bose D, Kümin M, Scarborough C, Matthews PC, Brent AJ, Lomas J, Gundle R, Rogers M, Taylor A, Angus B, Byren I, Berendt AR, Warren S, Fitzgerald FE, Mack DJF, Hopkins S, Folb J, Reynolds HE, Moore E, Marshall J, Jenkins N, Moran CE, Woodhouse AF, Stafford S, Seaton RA, Vallance C, Hemsley CJ, Bisnauthsing K, Sandoe JAT, Aggarwal I, Ellis SC, Bunn DJ, Sutherland RK, Barlow G, Cooper C, Geue C, McMeekin N, Briggs AH, Sendi P, Khatamzas E, Wangrangsimakul T, Wong THN, Barrett LK, Alvand A, Old CF, Bostock J, Paul J, Cooke G, Thwaites GE, Bejon P, and Scarborough M
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- Administration, Intravenous, Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents pharmacokinetics, Female, Humans, Intention to Treat Analysis, Male, Medication Adherence, Middle Aged, Treatment Outcome, Young Adult, Administration, Oral, Anti-Bacterial Agents administration & dosage, Bone Diseases, Infectious drug therapy, Joint Diseases drug therapy
- Abstract
Background: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication., Methods: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points., Results: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%)., Conclusions: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
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- 2019
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