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Abstract In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae. Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20–5.32) mg/L p

Abstract Antimicrobial resistance (AMR) and healthcare associated infections pose a significant threat globally. One key prevention strategy is to follow antimicrobial stewardship practices, in particular, to maximise targeted oral therapy and reduce the use of indwelling vascular devices for intravenous (IV) administration. Appreciating when an individual patient can switch from IV to oral antibiotic treatment is often non-trivial and not standardised. To tackle this problem we created a machine learning model to predict when a patient could switch based on routinely collected clinical parameters. 10,362 unique intensive care unit stays were extracted and two informative feature sets identified. Our best model achieved a mean AUROC of 0.80 (SD 0.01) on the hold-out set while not being biased to individuals protected characteristics. Interpretability methodologies were employed to create clinically useful visual explanations. In summary, our model provides individualised, fair, and interpretable predictions for when a patient could switch from IV-to-oral antibiotic treatment. Prospectively evaluation of safety and efficacy is needed before such technology can be applied clinically.

Abstract Despite technological advancements in infectious disease rapid diagnostic tests (RDTs) and use to direct therapy at the per-patient level, RDT utilisation in antimicrobial stewardship programmes (ASPs) is variable across low-to-middle income and high-income countries. Key insights from a panel of seven infectious disease experts from Colombia, Japan, Nigeria, Thailand, the UK, and the USA, combined with evidence from a literature review, were used to assess the value of RDTs in ASPs. From this, a value framework is proposed which aims to define the benefits of RDT use in ASPs, separate from per-patient benefits. Expert insights highlight that, to realise the value of RDTs within ASPs, effective implementation is key; actionable advice for choosing an RDT is proposed. Experts advocate the inclusion of RDTs in the World Health Organization Model List of essential in vitro diagnostics and in iterative development of national action plans.

Introduction: Central line-associated bloodstream infections (CLABSI) are an important clinical and public health issue, impacted by the purported increase in healthcare-associated infections (including CLABSI) during the COVID-19 pandemic. This review evaluates the impact of COVID-19 on CLABSI at a global level, to determine risk factors, effective preventive measures and microbiological epidemiology. Methods: A systematic literature review was performed using a PECO framework, with COVID-19 infection as the exposure measure and CLABSI rates as the main outcome of interest, pre- and during the pandemic. Results: Overall, most studies (17 of N=21) found a significant increase in CLABSI incidence/rates during the pandemic. Four studies showed a reduction (N=1) or no increase (N=3). High workload, redeployment, and ‘overwhelmed’ healthcare staff were recurrent risk-factor themes, likely to have negatively influenced basic infection control practices, including compliance with hand hygiene and line care bundles. Microbiological epidemiology was also impacted, with an increase in enterococcal infections and other pathogens. Conclusion: The COVID-19 pandemic significantly impacted CLABSI incidence/rates. Observations from the different studies highlight significant gaps in healthcare associated infections (HCAI) knowledge and practice during the pandemic, and the importance of identifying preventive measures effective in reducing CLABSI, essential to health system resilience for future pandemics. Central to this are changes to CLABSI surveillance, as reporting is not mandatory in many healthcare systems. An audit tool combined with regular assessments of the compliance with infection control measures and line care bundles also remains an essential step in the prevention of CLABSI.

Abstract Background European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria for methicillin-susceptible Staphylococcus aureus (MSSA) treatment with ceftriaxone are based upon high dose (4 g/day) rather than standard dose (2 g/day) posology. This is particularly relevant for invasive infections, and for patients managed via Outpatient Parenteral Antimicrobial Therapy (OPAT), but may result in increased drug toxicity. We quantified the incidence of neutropenia, thrombocytopenia and raised liver enzymes between standard and high dose ceftriaxone in adult patients. Method Adult outpatients prescribed ≥ 7 days of ceftriaxone therapy were identified, and clinical, pharmacological, and laboratory parameters extracted from electronic health records between May 2021 and December 2021. Incidence and median time to haematological and hepto-toxicity were analysed. Univariate odds ratios were calculated for neutrophil count and ALT levels with 95% confidence level and Chi squared/Fisher’s exact test used to identify statistical significance. Results Incidence of neutropenia was comparable between both groups; 8/47 (17%) in the 2 g group vs 6/39 (15.4%) in the 4 g group (OR 0.89 (95% CI 0.26–2.63), p > 0.999). Median time to neutropenia was 12 and 17 days in the 2 g and 4 g groups respectively. Thrombocytopenia was observed in 0/47 in the 2 g group compared with 3/39 (7.7%) in the 4 g group (p 0.089). Median time to thrombocytopenia was 7 days in the 4 g group. Elevated liver enzymes did not clearly correlate with ceftriaxone dosing; present in 5/47 (10.6%) and 2/39 (5.1%) for 2 g and 4 g respectively (OR 0.45 (95% CI 0.87–2.36), p 0.448). Treatment cessation due to any adverse effect was similar between both groups 2/47 (4.3%) for 2 g and 3/39 (7.7%) for 4 g (OR 1.86 (95% CI 0.36–10.92), p 0.655). Conclusions Increased adverse effects with 4 g (over 2 g) daily dosing of ceftriaxone was not observed in an OPAT population. However absolute development of haematological and liver dyscrasias was appreciable—monitoring of liver function and full blood count in patients receiving prolonged ceftriaxone is indicated irrespective of dosing.

Abstract Background To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making. Methods Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital. Results CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p

The decision on when it is appropriate to stop antimicrobial treatment in an individual patient is complex and under-researched. Ceasing too early can drive treatment failure, while excessive treatment risks adverse events. Under- and over-treatment can promote the development of antimicrobial resistance (AMR). We extracted routinely collected electronic health record data from the MIMIC-IV database for 18,988 patients (22,845 unique stays) who received intravenous antibiotic treatment during an intensive care unit (ICU) admission. A model was developed that utilises a recurrent neural network autoencoder and a synthetic control-based approach to estimate patients’ ICU length of stay (LOS) and mortality outcomes for any given day, under the alternative scenarios of if they were to stop vs. continue antibiotic treatment. Control days where our model should reproduce labels demonstrated minimal difference for both stopping and continuing scenarios indicating estimations are reliable (LOS results of 0.24 and 0.42 days mean delta, 1.93 and 3.76 root mean squared error, respectively). Meanwhile, impact days where we assess the potential effect of the unobserved scenario showed that stopping antibiotic therapy earlier had a statistically significant shorter LOS (mean reduction 2.71 days, p-value

Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described.Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-min sampling period, targeting a serum piperacillin concentration between 32 and 64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam.Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches.Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis.

Abstract 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 One hundred nineteen thousand five hundred eighty-four 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

The SARS-CoV-2 virus, which causes the COVID-19 pandemic, has had an unprecedented impact on healthcare requiring multidisciplinary innovation and novel thinking to minimize impact and improve outcomes. Wide-ranging disciplines have collaborated including diverse clinicians (radiology, microbiology, and critical care), who are working increasingly closely with data-science. This has been leveraged through the democratization of data-science with the increasing availability of easy to access open datasets, tutorials, programming languages, and hardware which makes it significantly easier to create mathematical models. To address the COVID-19 pandemic, such data-science has enabled modeling of the impact of the virus on the population and individuals for diagnostic, prognostic, and epidemiological ends. This has led to two large systematic reviews on this topic that have highlighted the two different ways in which this feat has been attempted: one using classical statistics and the other using more novel machine learning techniques. In this review, we debate the relative strengths and weaknesses of each method toward the specific task of predicting COVID-19 outcomes.

Abstract Background Bacterial ophthalmic infections are common. Empirical treatment with topical broad-spectrum antibiotics is recommended for severe cases. Antimicrobial resistance (AMR) to agents used for bacterial ophthalmic infections make it increasingly important to consider changing resistance patterns when prescribing, however UK data in this area are lacking. We evaluate the epidemiology and antimicrobial susceptibilities of ophthalmic pathogens across care settings and compare these with local and national antimicrobial prescribing guidelines. Methods A retrospective, multi-centre observational analysis was undertaken of ophthalmic microbiology isolates between 2009 and 2015 at a centralised North-West London laboratory (incorporating data from primary care and five London teaching hospitals). Data were analysed using descriptive statistics with respect to patient demographics, pathogen distribution (across age-groups and care setting), seasonality, and susceptibility to topical chloramphenicol, moxifloxacin, and fusidic acid. Results Two thousand six hundred eighty-one isolates (n = 2168 patients) were identified. The commonest pathogen in adults was Staphylococcus spp. across primary, secondary, and tertiary care (51.7%; 43.4%; 33.6% respectively) and in children was Haemophilus spp. (34.6%;28.2%;36.6%). AMR was high and increased across care settings for chloramphenicol (11.8%;15.1%;33.8%); moxifloxacin (5.5%;7.6%;25.5%); and fusidic acid (49.6%;53.4%; 58.7%). Pseudomonas spp. was the commonest chloramphenicol-resistant pathogen across all care settings, whilst Haemophilus spp. was the commonest fusidic acid-resistant pathogen across primary and secondary care. More isolates were recorded in spring (31.6%) than any other season, mostly due to a significant rise in Haemophilus spp. Conclusions We find UK national and local antimicrobial prescribing policies for ophthalmic infections may not be concordant with the organisms and antimicrobial susceptibilities found in clinical samples. We also find variations in microbial incidence related to patient age, clinical setting, and season. Such variations may have further important implications for prescribing practices and modification of antimicrobial guidelines.

Antimicrobial resistance (AMR) in populations experiencing war has yet to be addressed, despite the abundance of contemporary conflicts and the protracted nature of twenty-first century wars, in combination with growing global concern over conflict-associated bacterial pathogens. The example of the Syrian conflict is used to explore the feasibility of using existing global policies on AMR in conditions of extreme conflict. The available literature on AMR and prescribing behaviour in Syria before and since the onset of the conflict in March 2011 was identified. Overall, there is a paucity of rigorous data before and since the onset of conflict in Syria to contextualize the burden of AMR. However, post onset of the conflict, an increasing number of studies conducted in neighbouring countries and Europe have reported AMR in Syrian refugees. High rates of multidrug resistance, particularly Gram-negative organisms, have been noted amongst Syrian refugees when compared with local populations. Conflict impedes many of the safeguards against AMR, creates new drivers, and exacerbates existing ones. Given the apparently high rates of AMR in Syria, in neighbouring countries hosting refugees, and in European countries providing asylum, this requires the World Health Organization and other global health institutions to address the causes, costs, and future considerations of conflict-related AMR as an issue of global governance. Keywords: Syria, Antimicrobial resistance, Conflict, Refugees

Abstract Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance.

Abstract Background We report the development and evaluation of a web-based tool designed to facilitate student extra-curricular engagement in medical research through project matching students with academic supervisors. UK based university students were surveyed to explore their perceptions of undergraduate research, barriers and facilitators to current engagement. Following this, an online web-based intervention (www.ProjectPal.org) was developed to support access of students to research projects and supervisors. A pilot intervention was undertaken across a London-based university in January 2013 to February 2016. In March 2016, anonymised data were extracted from the prospective data log for analysis of website engagement and usage. Supervisors were surveyed to evaluate the website and student outputs. Results Fifty-one students responded to the electronic survey. Twenty-four (47%) reported frustration at a perceived lack of opportunities to carry out extra-curricular academic projects. Major barriers to engaging in undergraduate research reported were difficulties in identifying suitable supervisors (33/51; 65%) and time pressures (36/51; 71%) associated with this. Students reported being opportunistic in their engagement with undergraduate research. Following implementation of the website, 438 students signed up to ProjectPal and the website was accessed 1357 times. Access increased on a yearly basis. Overall, 70 projects were advertised by 35 supervisors. There were 86 applications made by students for these projects. By February 2016, the 70 projects had generated 5 peer-review publications with a further 7 manuscripts under peer-review, 14 national presentations, and 1 national prize. Conclusion The use of an online platform to promote undergraduate engagement with extra-curricular research appears to facilitate extra-curricular engagement with research. Further work to understand the impact compared to normal opportunistic practices in enhancing student engagement is now underway.

Abstract Background We developed a personalised antimicrobial information module co-designed with patients. This study aimed to evaluate the potential impact of this patient-centred intervention on short-term knowledge and understanding of antimicrobial therapy in secondary care. Methods Thirty previous patients who had received antibiotics in hospital within 12 months were recruited to co-design an intervention to promote patient engagement with infection management. Two workshops, containing five focus-groups were held. These were audio-recorded. Data were analysed using a thematic framework developed deductively based on previous work. Line-by-line coding was performed with new themes added to the framework by two researchers. This was used to inform the development of a patient information module, embedded within an electronic decision support tool (CDSS). The intervention was piloted over a four-week period at Imperial College Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires were developed and implemented to assess short term changes in patient knowledge and understanding and provide feedback on the intervention. Data were analysed using SPSS and NVIVO software. Results Within the workshops, there was consistency in identified themes. The participants agreed upon and co-designed a personalised PDF document that could be integrated into an electronic CDSS to be used by healthcare professionals at the point-of-care. Their aim for the tool was to provide individualised practical information, signpost to reputable information sources, and enhance communication between patients and healthcare professionals. Eighteen out of thirty in-patients consented to participant in the pilot evaluation with 15/18(83%) completing the study. Median (range) age was 66(22–85) years. The majority were male (10/15;66%). Pre-intervention, patients reported desiring further information regarding their infections and antibiotic therapy, including side effects of treatment. Deployment of the intervention improved short term knowledge and understanding of individuals infections and antibiotic management with median (IQR) scores improving from 3(2–5)/13 to 10(6–11)/13. 13/15(87%) reported that they would use the intervention again. Conclusion A personalised, patient-centred intervention improved understanding and short-term knowledge of infections and antibiotic therapy in participating patients’. Long term impact on attitudes and behaviours post discharge will be further investigated.

In the last years, there has been an increase of antimicrobial resistance rates around the world with the misuse and overuse of antimicrobials as one of the main leading drivers. In response to this threat, a variety of initiatives have arisen to promote the efficient use of antimicrobials. These initiatives rely on antimicrobial surveillance systems to promote appropriate prescription practices and are provided by national or global health care institutions with limited consideration of the variations within hospitals. As a consequence, physicians’ adherence to these generic guidelines is still limited. To fill this gap, this work presents an automated approach to performing local antimicrobial surveillance from microbiology data. Moreover, in addition to the commonly reported resistance rates, this work estimates secular resistance trends through regression analysis to provide a single value that effectively communicates the resistance trend to a wider audience. The methods considered for trend estimation were ordinary least squares regression, weighted least squares regression with weights inversely proportional to the number of microbiology records available and autoregressive integrated moving average. Among these, weighted least squares regression was found to be the most robust against changes in the granularity of the time series and presented the best performance. To validate the results, three case studies have been thoroughly compared with the existing literature: (i) Escherichia coli in urine cultures; (ii) Escherichia coli in blood cultures; and (iii) Staphylococcus aureus in wound cultures. The benefits of providing local rather than general antimicrobial surveillance data of a higher quality is two fold. Firstly, it has the potential to stimulate engagement among physicians to strengthen their knowledge and awareness on antimicrobial resistance which might encourage prescribers to change their prescription habits more willingly. Moreover, it provides fundamental knowledge to the wide range of stakeholders to revise and potentially tailor existing guidelines to the specific needs of each hospital.

Abstract Background Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4–6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p

Summary: Background: Enhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers. Methods: This first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK). The study was approved by London-Harrow Regional Ethics Committee. Volunteers were identified through emails sent to a healthy volunteer database from the Imperial College Clinical Research Facility. Volunteers, who had to be older than 18 years, were excluded if they had evidence of active infection, allergies to penicillin, were at high risk of skin infection, or presented with anaemia during screening. Participants wore a solid microneedle β-lactam biosensor for up to 6 h while being dosed at steady state with oral phenoxymethylpenicillin (five 500 mg doses every 6 h). On arrival at the study centre, two microneedle sensors were applied to the participant's forearm. Blood samples (via cannula, at −30, 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) and extracellular fluid (ECF; via microdialysis, every 15 min) pharmacokinetic (PK) samples were taken during one dosing interval. Phenoxymethylpenicillin concentration data obtained from the microneedles were calibrated using locally estimated scatter plot smoothing and compared with free-blood and microdialysis (gold standard) data. Phenoxymethylpenicillin PK for each method was evaluated using non-compartmental analysis. Area under the concentration–time curve (AUC), maximum concentration, and time to maximum concentration were compared. Bias and limits of agreement were investigated with Bland–Altman plots. Microneedle biosensor limits of detection were estimated. The study was registered with ClinicalTrials.gov, number NCT03847610. Findings: Ten healthy volunteers participated in the study. Mean age was 42 years (SD 14). Seven (70%) were men. Microdialysis and microneedle results were similar for phenoxymethylpenicillin ECF maximum concentration (0·74 mg/L vs 0·64 mg/L; 95% CI −0·24 to 0·44; p=0·53), time to maximum concentration (1·18 h vs 1·10 h; −0·52 to 0·67; p=0·79), and AUC (1·54 mg × h/L vs 1·67 mg × h/L; −1·10 to 0·85; p=0·79). In total, 440 time points were compared with mean difference between measurements −0·16 mg/L (95% CI −1·30 to 0·82). Mean phenoxymethylpenicillin AUCs for free serum and microneedle PK were similar (1·77 mg × h/L [SD 0·59] vs 1·67 mg × h/L [1·00]; −0·77 to 0·97; p=0·81). Median coefficient of variation between sensors within individuals was 7% (IQR 4–17). Limit of detection for the microneedles was estimated at 0·17 mg/L. Interpretation: This study is proof-of-concept of real-time, microneedle sensing of penicillin in vivo. Future work will explore microneedle use in patient populations, their role in data generation to inform dosing recommendations, and their incorporation into closed-loop control systems for automated drug delivery. Funding: National Institute for Health Research Imperial Biomedical Research Centre, Mérieux Foundation.

Abstract Background The uptake of improvement initiatives in infection prevention and control (IPC) has often proven challenging. Innovative interventions such as ‘serious games’ have been proposed in other areas to educate and help clinicians adopt optimal behaviours. There is limited evidence about the application and evaluation of serious games in IPC. The purposes of the study were: a) to synthesise research evidence on the use of serious games in IPC to support healthcare workers’ behaviour change and best practice learning; and b) to identify gaps across the formulation and evaluation of serious games in IPC. Methods A scoping study was conducted using the methodological framework developed by Arksey and O’Malley. We interrogated electronic databases (Ovid MEDLINE, Embase Classic + Embase, PsycINFO, Scopus, Cochrane, Google Scholar) in December 2015. Evidence from these studies was assessed against an analytic framework of intervention formulation and evaluation. Results Nine hundred sixty five unique papers were initially identified, 23 included for full-text review, and four finally selected. Studies focused on intervention inception and development rather than implementation. Expert involvement in game design was reported in 2/4 studies. Potential game users were not included in needs assessment and game development. Outcome variables such as fidelity or sustainability were scarcely reported. Conclusions The growing interest in serious games for health has not been coupled with adequate evaluation of processes, outcomes and contexts involved. Explanations about the mechanisms by which game components may facilitate behaviour change are lacking, further hindering adoption.

Background/Objectives:Aspergillus fumigatus is the leading cause of invasive aspergillosis. Treatment is hindered by the emergence of resistance to triazole antimycotic agents. Here, we present the prevalence of triazole resistance among clinical isolates at a major centralized medical mycology laboratory in London, United Kingdom, in the period 1998–2017.Methods: A large number (n = 1469) of clinical A. fumigatus isolates from unselected clinical specimens were identified and their susceptibility against three triazoles, amphotericin B and three echinocandin agents was carried out. All isolates were identified phenotypically and antifungal susceptibility testing was carried out by using a standard broth microdilution method.Results: Retrospective surveillance (1998–2011) shows 5/1151 (0.43%) isolates were resistant to at least one of the clinically used triazole antifungal agents. Prospective surveillance (2015–2017) shows 7/356 (2.2%) isolates were resistant to at least one triazole antifungals demonstrating an increase in incidence of triazole-resistant A. fumigatus in our laboratory. Among five isolates collected from 2015 to 2017 and available for molecular testing, three harbored TR34/L98H alteration in the cyp51A gene that are associated with the acquisition of resistance in the non-patient environment.Conclusion: These data show that historically low prevalence of azole resistance may be increasing, warranting further surveillance of susceptible patients.