Personalised antimicrobial management in secondary care

Background: The growing threat of Antimicrobial Resistance (AMR) requires innovative methods to promote the sustainable effectiveness of antimicrobial agents. Hypothesis: This thesis aimed to explore the hypothesis that personalised decision support interventions have the utility to enhance antimicrobial management across secondary care. Methods: Different research methods were used to investigate this hypothesis. Individual physician decision making was mapped and patient experiences of engagement with decision making explored using semi-structured interviews. Cross-specialty engagement with antimicrobial management was investigated through cross-sectional analysis of conference abstracts and educational training curricula. Artificial intelligence tools were developed to explore their ability to predict the likelihood of infection and provide individualised prescribing recommendations using routine patient data. Dynamic, individualised dose optimisation was explored through: (i) development of a microneedle based, electrochemical biosensor for minimally invasive monitoring of beta-lactams; and (ii) pharmacokinetic (PK)-pharmacodynamic (PD) modelling of a new PK-PD index using C-Reactive protein (CRP) to predict the pharmacodynamics of vancomycin. Ethics approval was granted for all aspects of work explored within this thesis. Results: Mapping of individual physician decision making during infection management demonstrated several areas where personalised, technological interventions could enhance antimicrobial management. At specialty level, non-infection specialties have little engagement with antimicrobial management. The importance of engaging surgical specialties, who have relatively high rates of antimicrobial usage and healthcare associated infections, was observed. An individualised information leaflet, co-designed with patients, to provide personalised infection information to in-patients receiving antibiotics significantly improved knowledge and reported engagement with decision making. Artificial intelligence was able to enhance the prediction of infection and the prescribing of antimicrobials using routinely available clinical data. Real-time, continuous penicillin monitoring was demonstrated using a microneedle based electrochemical sensor in-vivo. A new PK-PD index, using C-Reactive Protein, was able to predict individual patient response to vancomycin therapy at 96-120 hours of therapy. Conclusion: Through co-design and the application of specific technologies it is possible to provide personalised antimicrobial management within secondary care.Open Acces

Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study.

BACKGROUND: The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions. METHODS: Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached. RESULTS: Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing 'optimal' care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort. CONCLUSION: Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers

Antimicrobials : a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.Peer reviewe

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection

ObjectivesIn 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.MethodsMinimum inhibitory concentrations (MICs) of clinical NDM-producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of the ATM breakpoint after the addition of CAZ/AVI was explored. A CAZ/AVI Etest/ATM disc method was compared with broth dilution.ResultsOf 43 isolates, 33 (77%) were ATM resistant (median [range] MIC = 56 [16-512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC ConclusionCAZ/AVI+ATM demonstrated significant synergy in most ATM-resistant NDM-producing Enterobacterales. The Etest/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory