Imperial College London

Professor Mark Gilchrist

Faculty of MedicineDepartment of Infectious Disease

Professor of Practice
 
 
 
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m.gilchrist

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

56 results found

Sime FB, Wallis S, Jamieson C, Hills T, Gilchrist M, Santillo M, Seaton RA, Drummond F, Roberts Jet al., 2023, Evaluation of the stability of temocillin in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy in accordance with the requirements of the UK NHS Yellow Cover Document, EUROPEAN JOURNAL OF HOSPITAL PHARMACY, Vol: 30, Pages: E76-E81, ISSN: 2047-9956

Journal article

Rimmer S, Barnacle J, Gibani M, Wu M-S, Dissanayake O, Mehta R, Herdman T, Gilchrist M, Muir D, Ebrahimsa U, Mora-Peris B, Dosekun O, Garvey L, Peters J, Davies F, Cooke G, Abbara Aet al., 2023, The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort, International Journal of Infectious Diseases, Vol: 126, Pages: 48-53, ISSN: 1201-9712

Objectives: Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in non-endemic countries. Our aim was to characterise diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification, and to describe a virtual care model.Methods: We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV PCR testing, 70 were confirmed positive and 70 negative. Data were compared to generate odds ratios of demographic and clinical features.Results: Positive patients were predominantly cis-male (99%) and self-identified as gay, bisexual and other men who have sex with men (GBMSM) (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (OR 7.69 [95% CI 3.58, 16.51]). Positive patients were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) compared with negative controls. 79% of patients engaged with virtual ward follow-up.Conclusions: These data can inform a risk-based approach to management of suspected monkeypox in GBMSM populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPXV outbreak.

Journal article

Ramnarayan P, Mitting R, Whittaker E, Marcolin M, O'Regan C, Sinha R, Bennett A, Moustafa M, Tickner N, Gilchrist M, Kershaw A, Rampling Tet al., 2022, Neonatal Monkeypox Virus Infection, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 387, Pages: 1618-1620, ISSN: 0028-4793

Journal article

Arkell P, Wilson R, Watkins K, Antcliffe DB, Gilchrist M, Wilson M, Rawson TM, Holmes Aet al., 2022, Application of therapeutic drug monitoring to the treatment of bacterial central nervous system infection: a scoping review, Journal of Antimicrobial Chemotherapy, Vol: 77, Pages: 3408-3413, ISSN: 0305-7453

BackgroundBacterial central nervous system (CNS) infection is challenging to treat and carries high risk of recurrence, morbidity, and mortality. Low CNS penetration of antibiotics may contribute to poor clinical outcomes from bacterial CNS infections. The current application of therapeutic drug monitoring (TDM) to management of bacterial CNS infection was reviewed.MethodsStudies were included if they described adults treated for a suspected/confirmed bacterial CNS infection and had antibiotic drug concentration(s) determined that affected individual treatment.ResultsOne-hundred-and-thirty-six citations were retrieved. Seventeen manuscripts were included describing management of 68 patients. TDM for vancomycin (58/68) and the beta-lactams (29/68) was most common. Timing of clinical sampling varied widely between studies and across different antibiotics. Methods for setting individual PK-PD targets, determining parameters and making treatment changes varied widely and were sometimes unclear.DiscussionDespite increasing observational data showing low CNS penetration of various antibiotics, there are few clinical studies describing practical implementation of TDM in management of CNS infection. Lack of consensus around clinically relevant CSF PK-PD targets and protocols for dose-adjustment may contribute. Standardised investigation of TDM as a tool to improve treatment is required, especially as innovative drug concentration-sensing and PK-PD modelling technologies are emerging. Data generated at different centres offering TDM should be open access and aggregated to enrich understanding and optimize application.

Journal article

Wilson R, Arkell P, Riezk A, Wheeler G, Gilchrist M, Hope W, Holmes A, Rawson TMet al., 2022, Addition of probenecid to oral beta-lactam antibiotics: a systematic review and meta-analysis, Journal of Antimicrobial Chemotherapy, Vol: 77, Pages: 2364-2372, ISSN: 0305-7453

Objective: Explore literature comparing the pharmacokinetic and clinical outcomes from addition of probenecid to oral beta-lactams.Data sources: Medline and EMBASE were searched from inception to December 2021.Study eligibility criteria: All English language studies comparing the addition of probenecid (intervention) to an oral beta-lactam (flucloxacillin, penicillin-V, amoxicillin(+/-clavulanate), cephalexin, cefuroxime-axetil) alone (comparator).Risk of bias: Risk of Bias in Non-randomised studies of interventions (ROBINS-I) and Risk of Bias for Randomised studies 2 (ROB-2) tools were used.Methods of data synthesis: Data on antibiotic therapy, infection diagnosis, primary and secondary outcomes relating to pharmacokinetics and clinical outcomes plus adverse events were extracted and reported descriptively. For a subset of studies comparing treatment failure between probenecid and control groups, meta-analysis was performed. Results: Overall, 18/295 (6%) abstracts screened were included. Populations, methodology, and outcome data were heterogenous. Common populations included healthy volunteer (9/18;50%) and gonococcal infection (6/18;33%). Most studies were cross-over trials (11/18;61%) or parallel arm randomised trial (4/18;22%). Where pharmacokinetic analyses were performed, addition of probenecid to oral beta-lactams increased total AUC (7/7;100¬%), peak observed concentration (Cmax,5/8;63%), and serum half-life (t1/2,6/8;75%). Probenecid improved PTA (2/2;100%). Meta-analysis of 3105 (2258 intervention, 847 control) patients treated for gonococcal disease demonstrated a relative risk of treatment failure in the random effects model of 0.33 (95%CI:0.20-0.55; I2=7%), favouring probenecid. Conclusion: Probenecid boosted beta-lactam therapy is associated with improved outcomes in gonococcal disease. Pharmacokinetic data suggest that probenecid boosted oral beta-lactam therapy may have a broader application, but appropriately powered mechanistic and efficacy st

Journal article

Rawson TM, Eigo T, Wilson R, Husson F, Dhillon R, Seddon O, Holmes A, Gilchrist Met al., 2022, Exploring patient acceptance of research within Complex oral and IV Outpatient Parenteral Antimicrobial Therapy (COpAT) networks, JAC-Antimicrobial Resistance, Vol: 4, ISSN: 2632-1823

Journal article

Jamieson C, Ozolina L, Seaton RA, Gilchrist M, Hills T, Drummond F, Wilkinson ASet al., 2022, Assessment of the stability of citrate-buffered piperacillin/tazobactam for continuous infusion when stored in two commercially available elastomeric devices for outpatient parenteral antimicrobial chemotherapy: a study compliant with the NHS Yellow Cover Document requirements, EUROPEAN JOURNAL OF HOSPITAL PHARMACY, Vol: 29, Pages: 212-216, ISSN: 2047-9956

Journal article

Rawson TM, Brzeska-Trafny I, Maxfield R, Almeida M, Gilchrist M, Gonzalo X, Moore L, Donaldson H, Davies Fet al., 2022, A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales infection, Journal of Global Antimicrobial Resistance, Vol: 29, Pages: 558-562, ISSN: 2213-7165

Background:In response to infection with New Delhi Metallo-beta-lactamase (NDM) producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM producing Enterobacterales.Methods:Minimum inhibitory concentration (MIC) of clinical NDM producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of ATM breakpoint following the addition of CAZ/AVI was explored. A CAZ/AVI E-test/ATM disc method was compared to broth dilution.Results:Of 43 isolates, 33/43 (77%) isolates were ATM resistant (median [range] MIC=56 [16 – 512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4mg/L) in 29/33 (89%) of resistant isolates. Overall, the E-test/disc method correlated with findings from broth dilution in 35/43 (81%) of cases. E-test/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%.Conclusion:CAZ/AVI+ATM demonstrated significant synergy in most ATM resistant NDM producing Enterobacterales. The E-test/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory.

Journal article

Gilchrist M, Barr D, Drummond F, Muir A, Williams J, Scriven J, Snape S, Hemsley C, Durojaiye CO, Patel S, Seaton RAet al., 2022, Outpatient parenteral antimicrobial therapy (OPAT) in the UK: findings from the BSAC National Outcomes Registry (2015-19), JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 77, Pages: 1481-1490, ISSN: 0305-7453

Journal article

Emilie C, de Nocker P, Saïdani N, Gilchrist M, Seaton RA, Patel S, Beraud G, Kofteridis D, Schouten J, Thilly N, Berrevoets M, Hulscher M, Buyle F, Pulcini C, ESGAP-BSAC OPAT Survey Working Groupet al., 2022, Survey of delivery of parenteral antimicrobials in non-inpatient settings across Europe., Int J Antimicrob Agents, Vol: 59

Delivery of parenteral antimicrobials in non-inpatient settings (DPANS) may be through a dedicated outpatient parenteral antimicrobial therapy (OPAT) service, co-ordinated by hospital- or community-based specialised teams, or via an infusion service involving community-based health professionals (nurses, general practitioners) without centralised hospital oversight, or through ad hoc arrangements. DPANS varies among countries. Our objective was to describe how DPANS is organised at a national level in European countries. A survey (65-item self-administered questionnaire) was conducted from February-June 2019 among infection specialists in 34 European countries on behalf of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) and the British Society for Antimicrobial Chemotherapy (BSAC) OPAT initiative. Most countries (28/34; 82.4%) participated in the survey. DPANS was available in almost all (27/28; 96.4%) responding countries. DPANS was predominantly provided either via specialised OPAT services (17/28; 60.7%) or via infusion services (16/28; 57.1%), with 11 countries (39.3%) providing both services. A formal OPAT team structure with specifically trained staff was reported in only six countries (6/17; 35.3%). Some countries (4/28; 14.3%) had no structured services but practiced DPANS via ad hoc arrangements. The costs of all stages of the process were covered for patients managed by specialised OPAT/infusion services, either completely, partially or for specific patient groups in the majority (20/28; 71.4%) of countries. The main barriers to implement OPAT/infusion services were lack of organisational structure or guidelines. In conclusion, DPANS with respect to availability and organisation is highly heterogeneous in Europe. National/European guidelines may help improve and standardise DPANS.

Journal article

Arkell P, Wilson R, Antcliffe DB, Gilchrist M, Noel AR, Wilson M, Barnes SC, Watkins K, Holmes A, Rawson TMet al., 2022, A pilot observational study of CSF vancomycin therapeutic drug monitoring during the treatment of nosocomial ventriculitis., Journal of Infection, ISSN: 0163-4453

Journal article

Rawson TM, Wilson R, Moore L, Macgowan A, Lovering A, Bayliss M, Kyriakides M, Gilchrist M, Roberts J, Hope W, Holmes Aet al., 2021, Exploring the pharmacokinetics of phenoxymethylpenicillin (Penicillin-V) in adults: a healthy volunteer study, Open Forum Infectious Diseases, Vol: 8, Pages: 1-4, ISSN: 2328-8957

This healthy volunteer study aimed to explore Phenoxymethylpenicillin (Penicillin-V) pharmacokinetics (PK) to support the planning of large, dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentration was determined and a base population PK model were fitted to the data.

Journal article

Dimitrova M, Gilchrist M, Seaton RA, 2021, Outpatient parenteral antimicrobial therapy (OPAT) versus inpatient care in the UK: a health economic assessment for six key diagnoses., BMJ Open, Vol: 11

OBJECTIVES: To compare costs associated with different models of outpatient parenteral antimicrobial therapy (OPAT) delivery with costs of inpatient (IP) care across key infection groups managed via OPAT in the UK. DESIGN: A cost-minimisation design was used due to evidence of similarities in patient and treatment outcomes between OPAT and IP care. A bottom-up approach was undertaken for the evaluation of OPAT associated costs. The British Society of Antimicrobial Chemotherapy National Outcomes Registry System was used to determine key infection diagnoses, mean duration of treatment and most frequent antibiotics used. SETTING: Several OPAT delivery settings were considered and compared with IP care. INTERVENTIONS: OPAT models considered were OP clinic model, nurse home visits, self (or carer)-administration by a bolus intravenous, self-administration by a commercially prefilled elastomeric device, continuous intravenous infusion of piperacillin with tazobactam or flucloxacillin with elastomeric device as OP once daily and, specifically for bone and joint and diabetic foot infections, complex outpatient oral antibiotic therapies. RESULTS: Base case and a range of scenario results showed all evaluated OPAT service delivery models to be less costly than IP stay of equivalent duration. The extent of savings varied by OPAT healthcare delivery models. Estimated OPAT costs as a proportion of IP costs were estimated at 0.23-0.53 (skin and soft-tissue infections), 0.34-0.46 (complex urinary tract infections), 0.23-0.51 (orthopaedic infections), 0.24-0.42 (diabetic foot infections) 0.40-0.56 (exacerbations of bronchiectasis) and 0.25-0.42 (intra-abdominal infections). Partial or full complex oral antibiotic therapies in orthopaedic or diabetic foot infections costs were estimated to be 0.13-0.26 of IP costs. Main OPAT costs were associated with staff time and antimicrobial medications. CONCLUSIONS: OPAT is a cost-effective use of National Health Service resources for the trea

Journal article

Jamieson C, Drummond F, Hills T, Ozolina L, Gilchrist M, Seaton RA, Santillo M, Wilkinson A-S, Allwood MCet al., 2021, Assessment of ceftolozane/tazobactam stability in elastomeric devices and suitability for continuous infusion via outpatient parenteral antimicrobial therapy, JAC-ANTIMICROBIAL RESISTANCE, Vol: 3

Journal article

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

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

Journal article

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

Background – We investigated for change in blood stream infections (BSI) with Enterobacterales, coagulase negative staphylococci (CoNS), Streptococcus pneumoniae, and Staphylococcus aureus during the first UK wave of SARS-CoV-2 across five London hospitals.Methods – A retrospective multicentre ecological analysis was undertaken evaluating all blood cultures taken from adults from 01 April 2017 to 30 April 2020 across five acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation.Results –119,584 blood cultures were included. At the height of the UK SARS-CoV-2 first wave in April 2020, Enterobacterales bacteraemias were at an historic low across two London trusts (63/3814, 1.65%), whilst all CoNS BSI were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p=0.013), CoNS central line associated BSIs (CLABSI) (p<0.01) and CoNS non-CLABSI (p<0.01), when compared with prior periods, even allowing for seasonal variation. S. pneumoniae (p=0.631) and S. aureus (p=0.617) BSI did not vary significant throughout the study period. Conclusions – Significantly fewer than expected Enterobacterales BSI occurred during the UK peak of the COVID-19 pandemic; identifying potential causes, including potential unintended consequences of national self-isolation public health messaging, is essential. High rates of CoNS BSI, with evidence of increased CLABSI, but also likely contamination associated with increased use of personal protective equipment, may result in inappropriate antimicrobial use and indicates a clear area for intervention during further waves.

Journal article

Chavda A, Gilchrist M, Samarasinghe D, 2021, Education: A compassionate use of cefiderocol to treat osteomyelitis caused by an XDR Pseudomonas aeruginosa., JAC Antimicrob Resist, Vol: 3, Pages: i18-i20

We report a 59-year-old male with left leg osteomyelitis caused by an XDR Pseudomonas aeruginosa strain following a road traffic accident. Limited treatment options and adverse antimicrobial reaction led to consideration of cefiderocol together with appropriate surgical intervention. Improved bony remodelling over the tibia and fibula was observed with good bony alignment and no adverse features. Physiotherapy support was continued for 4 months following treatment, which resulted in good functional mobility, improved proprioception and full ability to bear weight. This case also adds to multiple reports that describe safe and successful use of cefiderocol to treat MDR, aerobic Gram-negative infections.

Journal article

Wali S, Teh JJ, Mollier J, Gilchrist M, Miskry Tet al., 2021, Tubo-ovarian abscess management at a centre offering outpatient intravenous antibiotic therapy, RCOG National Trainees Conference (NTC) 2021

Conference paper

Satta G, Youngstein T, Lightstone L, Gilchrist M, COVID-19 treatment guidelines working group at Imperial College Healthcare NHS Trustet al., 2021, The utility of a local multidisciplinary working group to oversee the establishment of rapidly evolving standards of care and to support trial recruitment during the COVID-19 pandemic, Clinical medicine (London, England), Vol: 21, Pages: e287-e289, ISSN: 1470-2118

Coronavirus disease 2019 (COVID-19) was first identified in December 2019 in Wuhan, China. The first analyses of cases described high numbers of critically ill patients requiring intensive care admission with significant late inflammatory features. By the time the first cases of SARS-CoV-2 infection were diagnosed in the UK, a wide range of drugs were under consideration and it became clear that the input of clinicians covering all organ systems (in particular, infectious diseases, haematology, rheumatology, renal medicine and intensive care) and of expert specialist pharmacists was necessary at the local level. Thus, an expert multidisciplinary (MDT) group within our organisation was convened to offer a standardised approach and robust clinical governance for the treatment of COVID-19 patients admitted to our hospitals and rapidly develop standards of care as evidence evolved. This commentary explores the methods and mechanisms for creating an MDT COVID-19 treatment working group which are applicable to any hospital likely to admit and care for high numbers of COVID-19 patients and demonstrates how the structure and governance of the group allowed for rapid adoption of both dexamethasone and tocilizumab into standard of care as data became available.

Journal article

Zhu N, Aylin P, Rawson T, Gilchrist M, Majeed A, Holmes Aet al., 2021, Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves, Clinical Microbiology and Infection, Vol: 27, Pages: 762-768, ISSN: 1198-743X

ObjectivesWe investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London.MethodsIndividual prescribing records between 2015 and 2020 for 2 million residents in north west London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London.ResultsRecords covering 366 059 patients, 730 001 antibiotic items and 848 201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum “Access” antibiotic, prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of “Watch” antibiotics used decreased during the peak in COVID-19.DiscussionA sustained reduction in community antibiotic prescribing has been observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed.

Journal article

Ghani R, Mullish BH, McDonald JAK, Ghazy A, Williams HRT, Brannigan ET, Mookerjee S, Satta G, Gilchrist M, Duncan N, Corbett R, Innes AJ, Pavlu J, Thursz MR, Davies F, Marchesi JRet al., 2021, Disease prevention not decolonization – a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms, Clinical Infectious Diseases, Vol: 72, Pages: 1444-1447, ISSN: 1058-4838

Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.

Journal article

Rawson TM, Hernandez B, Wilson R, Wilson R, Ming D, Herrero P, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Georgiou P, Holmes Aet al., 2021, Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19, JAC-Antimicrobial Resistance, Vol: 3, Pages: 1-4, ISSN: 2632-1823

Background: Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during COVID-19.Methods: Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted. Demographic, blood test, and microbiology data for individuals with and without SARS-CoV-2 positive PCR were obtained. A Gaussian-Naïve Bayes (GNB), Support Vector Machine (SVM), and Artificial Neuronal Network (ANN) were trained and compared using the area under the receiver operating characteristic curve (AUCROC). The best performing algorithm (SVM with 21 blood test variables) was prospectively piloted in July 2020. AUCROC was calculated for the prediction of a positive microbiological sample within 48 hours of admission. Results: A total of 15,599 daily blood profiles for 1,186 individual patients were identified to train the algorithms. 771/1186 (65%) individuals were SARS-CoV-2 PCR positive. Clinically significant microbiology results were present for 166/1186 (14%) patients during admission. A SVM algorithm trained with 21 routine blood test variables and over 8000 individual profiles had the best performance. AUCROC was 0.913, sensitivity 0.801, and specificity 0.890. Prospective testing on 54 patients on admission (28/54, 52% SARS-CoV-2 PCR positive) demonstrated an AUCROC of 0.960 (0.90-1.00). Conclusion: A SVM using 21 routine blood test variables had excellent performance at inferring the likelihood of positive microbiology. Further prospective evaluation of the algorithms ability to support decision making for the diagnosis of bacterial infection in COVID-19 cohorts is underway.

Journal article

Boyd SE, Vasudevan A, Moore LSP, Brewer C, Gilchrist M, Costelloe C, Gordon AC, Holmes AHet al., 2020, Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case-control study, Journal of Global Antimicrobial Resistance, Vol: 22, Pages: 826-831, ISSN: 2213-7165

BACKGROUND: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.

Journal article

Hughes S, Gilchrist M, Heard K, Hamilton R, Sneddon Jet al., 2020, Treating infections caused by carbapenemase-producing Enterobacterales (CPE): a pragmatic approach to antimicrobial stewardship on behalf of the UKCPA Pharmacy Infection Network (PIN)., JAC Antimicrob Resist, Vol: 2

The emergence of carbapenemase-producing Enterobacterales (CPE) as a major cause of invasive infection both within the UK and internationally poses a very real concern for all providers of healthcare. The burden of morbidity and mortality associated with CPE infections is well described. The need for early, targeted, effective and safe antimicrobial therapy remains key for the management of these infected patients yet reliable antimicrobial treatment options remain scarce. In the absence of a universal treatment for these CPE invasive infections, individual treatment options tailored to susceptibilities and severity of infection are required. This working group from within the UK Clinical Pharmacy Association (UKCPA) Pharmacy Infection Network has developed evidence-based treatment recommendations to support infection specialists in managing these complex infections. A systematic review of peer-reviewed research was performed and analysed. We report consensus recommendations for the management of CPE-associated infections. The national expert panel makes therapeutic recommendations regarding the pharmacokinetic and pharmacodynamic properties of the drugs and pharmacokinetic targets, dosing, dosage adjustment and monitoring of parameters for novel and established antimicrobial therapies with CPE activity. This manuscript provides the infection specialist with pragmatic and evidence-based options for the management of CPE infections.

Journal article

Rawson TM, Moore LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes Aet al., 2020, Response to Dudoignon et al., Clin Infect Dis

Journal article

Rawson TM, Moore L, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes Aet al., 2020, Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing, Clinical Infectious Diseases, Vol: 71, Pages: 2459-2468, ISSN: 1058-4838

BackgroundTo explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection.MethodsMEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed.Results1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus.For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described.For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.ConclusionsDespite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently requi

Journal article

Honeyford K, Cooke GS, Kinderlerer A, Williamson E, Gilchrist M, Holmes Aet al., 2020, Evaluating a digital sepsis alert in a London multisite hospital network: a natural experiment using electronic health record data (vol 27, pg 274, 2020), JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION, Vol: 27, Pages: 501-501, ISSN: 1067-5027

Journal article

Honeyford C, Cooke G, Kinderlerer A, Williamson E, Gilchrist M, Holmes A, Glampson B, Mulla A, Costelloe Cet al., 2020, Evaluating a digital sepsis alert in a London multi-site hospital network: a natural experiment using electronic health record data, Journal of the American Medical Informatics Association, Vol: 27, Pages: 274-283, ISSN: 1067-5027

Objective: To determine the impact of a digital sepsis alert on patient outcomes in a UK multi-site hospital network. Methods:A natural experiment utilising the phased introduction (without randomisation) of a digital sepsis alert into a multi-site hospital network. Sepsis alerts were either visible to clinicans (patients in the ‘intervention’ group) or running silently and not visible (the control group). Inverse probability of treatment weighted multivariable logistic regression was used to estimate the effect of the intervention on individual patient outcomes.Outcomes:In-hospital 30-day mortality (all inpatients), prolonged hospital stay (≥7 days) and timely antibiotics (≤60minutes of the alert) for patients who alerted in the Emergency Department. Results: The introduction of the alert was associated with lower odds of death (OR:0.76; 95%CI:(0.70, 0.84) n=21183); lower odds of prolonged hospital stay ≥7 days (OR:0.93; 95%CI:(0.88, 0.99) n=9988); and in patients who required antibiotics, an increased odds of receiving timely antibiotics (OR:1.71; 95%CI:(1.57, 1.87) n=4622).Discussion: Current evidence that digital sepsis alerts are effective is mixed. In this large UK study a digital sepsis alert has been shown to be associated with improved outcomes, including timely antibiotics. It is not known whether the presence of alerting is responsible for improved outcomes, or whether the alert acted as a useful driver for quality improvement initiatives.Conclusions: These findings strongly suggest that the the introduction of a network-wide digital sepsis alert is associated with improvements in patient outcomes, demonstrating that digital based interventions can be successfully introduced and readily evaluated.

Journal article

Bauer KA, Kullar R, Gilchrist M, File TMet al., 2019, Antibiotics and adverse events: the role of antimicrobial stewardship programs in 'doing no harm'., Curr Opin Infect Dis, Vol: 32, Pages: 553-558

PURPOSE OF REVIEW: Antimicrobial resistance (AMR) is a global threat worldwide, with deaths associated with AMR infections projected to exceed 10 million per year by the year 2050. The overuse and misuse of antibiotics is the primary driver of this resistance, with up to 50% of antibiotics prescribed in the hospital setting being either unnecessary or inappropriate. Antimicrobial stewardship (AMS) programs (ASPs) can mitigate some of this resistance, with the benefits well recognized; however, if we are to truly advance the state of AMS, the principles and practices should align with patient safety. RECENT FINDINGS: In a recent evaluation, among 1488 adult patients receiving systemic antibiotic therapy, 298 (20%) experienced at least one antibiotic-associated adverse drug event (ADE). Fifty-six (20%) nonclinically indicated antibiotic regimens were associated with an ADE. It is also well recognized that besides ADEs, the inappropriate use of antibiotics is associated the development of multidrug-resistant infections and Clostridium difficile infection. SUMMARY: Currently, there is a significant gap in ASPs correlating initiatives with patient safety goals, including reductions in antibiotic-associated ADEs and multidrug-resistant infections. Therefore, in this article, we provide the rationale for why ASPs are best suited to lead a collaborative effort to prevent antibiotic-associated ADEs and multidrug-resistant infections.

Journal article

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