University College London

Provide a brief overview of your project?
The INHALE study is a comprehensive research programme designed to explore the utility of molecular diagnostics for improving antimicrobial stewardship in the treatment of hospital-acquired pneumonia (HAP) in UK critical care. Hospital acquired and ventilators- associated pneumonias (VAP) cause significant morbidity and mortality among hospital in-patients, while also acting as a major driver of antimicrobial use. Standard microbiological culture to diagnose the infection takes 2-3 days and often a causative pathogen is not isolated.

In the first phase of INHALE we evaluated the performance of three different rapid molecular tests for the diagnosis of HAP/VAP, alongside an observational study of this patient group at four participating ICUs. Based on these results, we chose the Biofire Pneumonia Panel for progression to the next phase, a randomised controlled trial (RCT). In the INHALE RCT the Biofire Pneumonia Panel is run directly at the point of care at 12 participating ICUs across England. The test is a ‘sample-in, answer-out’ diagnostic test capable of identifying 37 pathogens and antimicrobial resistance genes in 1h15min, with limited hands on time. In the trial, patients randomised to the intervention arm will have a Pneumonia Panel run on the ICU by research nurses or clinical staff. The result is then delivered to the treating clinician alongside a prescribing algorithm designed to help front-line ICU staff interpret the result and prescribe according to principles of good antimicrobial stewardship. Control arm patients receive standard of care. The primary outcomes of the study are more active and proportionate prescribing at 24h and equivalence of clinical cure at 14 days. A behavioural arm investigates clinician’s attitudes and willingness to prescribe according to the rapid test results. The study opened to recruitment in summer 2019 and has recruited just under 200 patients to date. It is due to complete in March 2021.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.

1. Establishing a framework for the comprehensive evaluation of molecular diagnostics designed to improve antimicrobial prescribing
2. Demonstrating that nucleic acid based tests are more sensitive than conventional culture for the diagnosis of pneumonia, with the latter being highly variable depending on the laboratory performing it.
3. Demonstrating that a rapid syndromic diagnostic test can be successfully deployed directly at the point of care in ICU and be used to make antimicrobial prescribing decisions.

How is the project to be developed in the future?
Once the RCT is complete we intend to work closely with various national stakeholders to ensure that our results are broadly disseminated, and where possible incorporated into NHS guidance on adoption of molecular diagnostics for HAP and VAP.

NHS Somerset Foundation Trust

Provide a brief overview of your project?
The aim of this QI project was to achieve 25% reduction from baseline in 12 weeks and 50% in 6 months in the rate measuring the association between positive urine dipsticks for UTI diagnosis and antibiotic treatment in patients aged 65 and over across GP practices in the county.
The intervention consisted in sharing practice-level data on episodes of care (EoC) in the preceding 28-days’ period linking UTI antibiotic prescribing with a positive dipstick result, also presented as benchmark data. The underlying principles were based on the COM-B behaviour change model.

A PDSA cycle was undertaken by applying the intervention to two enthusiastic low performing GP practices followed by weekly updates for 4 weeks.

The next step involved obtaining leadership agreement to spread the intervention to include all 65 GP practices. The novel methodology was also set up as a bespoke automatic Eclipse Live alert showing individual EoC. The latter and benchmark data broken down by GP practice were shared via email with primary care leads, with updates 3, 5 and 8 weeks later.

Following a successful 4-week PDSA cycle, the intervention was applied to all GP practices and clinicians rapidly engaged with the novel data combining clinical and prescribing parameters leading to significant change. Within 3 months the aim targets of this QI project were achieved suggesting improvement demonstrated by a more than halved rate in the association between dipsticks and UTI antibiotic in patients aged 65 and over.

The new automatic Eclipse Live alert provides weekly reporting of EoC and is intended to contribute to consistency and sustainability with the onus on clinicians to monitor progress and need for improvement.

In conclusion, this QI project illustrates how change in culture and behaviour can be positively influenced by evidence-based references, peer comparison, and effectively communicating meaningful and specific data.
Please cite 3 examples of outcomes or impacts from the project on tackling AMR.
The rationale for this project was based on the premise that urine dipsticks are an unreliable tool to diagnose urine tract infection (UTI) in patients aged 65 and over are a driver for inappropriate prescribing.

The process measure was based on the rate variation of Episodes of Care (EoC) in the preceding 28-days’ period linking positive dipstick results to antibiotics’ prescribing per 1,000 patients aged 65 and over.

At Week 4 of the PDSA cycle GP practices had reduced the rate by 47% and 29%.

At countywide level four weeks after spreading the intervention the overall rate reduction was 42% against a target of 25% (rate level reduced from 3.21 to 1.86; EoC events reduced from 452 to 262).

The second milestone target of 50% reduction at 6 months was achieved by Week 13 (reduction = 54.5%; rate level = 1.46; EoC events = 205).

The previous 12 months of UTI antibiotics’ consumption for patients aged 65 and over showed no significant variation for pilot practices or county up to February 2020.
How is the project to be developed in the future?

Suggested future work included:

• continued monitoring of local Eclipse Amber alert by new AMS lead
• monitoring UTI antibiotic consumption
• triangulation with E Coli BSI data and MSU lab demand once available
• clinical time and cost savings associated with reduction in use of urine dipsticks

Wirral University Teaching Hospital

Provide a brief overview of your project?
The COVID-19 pandemic has resulted in a large number of radiologically proven pneumonias, associated with increased markers of inflammation (e.g. CRP, WCC) and ongoing fever. Clinicians cannot ascertain if this clinical picture is viral or bacterial in origin and thus frequently commence antibiotic treatment for the potentially reversible pneumonia and escalate therapy if patients do not respond to therapy. The resulting long treatment courses could be avoided if secondary bacterial infection could be reliably excluded.

Procalcitonin (PCT) is a precursor of the hormone calcitonin, released into the bloodstream upon bacterial insult, thus allowing differentiation of bacterial infection from viral/fungal infection. There is also evidence to support the use of PCT as an indicator of resolution of bacterial infection and as such, the test can be used to aid patient monitoring and guide antibiotic cessation.

Wirral University Teaching Hospitals (WUTH) trialled PCT to facilitate antibiotic related decision making in patients with COVID-19 under the care of respiratory physicians or intensivists. The assay was undertaken on day 3 of antibiotic therapy when all necessary additional clinical information was also available. A PCT result of <0.25ng/ml, indicated the infection was not bacterial and antibiotics could be stopped.

A baseline audit of antibiotic course length (123 COVID -19 positive patients) demonstrated a total course length of 7.3 antibiotic treatment days. The audit of the first 100 patients who received a PCT test demonstrated;

• 59 patients had a PCT <0.25ng/ml
• Resultant antibiotic cessation facilitated 96 antibiotic days saved. This excludes potential escalations of treatment that may have occurred in patients whose antibiotics had been stopped.
• Reduction of total course length of 1.7 days to 5.6 days in patients with PCT <0.25ng/ml.
• 10% increase in patients whose antibiotics stopped at or before day 3 of treatment.
• 4% reduction in course lengths >7 days.

Please cite 3 examples of outcomes or impacts from the project on tackling AMR.

1. 1. Use of PCT assays enabled reduction in antibiotic course length from 7.3 days to 5.6 days for patients with a low PCT (<0.25ng/ml).
   There is potential to reduce this further to closer to 3 days when clinicians are more familiar with PCT and its use.
2. 2. The proportion of patients whose antibiotics were stopped at or before the 72 hour clinical review rose by 10%.
   As this practice of review of cessation of antibiotics becomes more common across the Trust, if PCT is further rolled out, this will facilitate a change in culture where antibiotics are more frequently stopped at 72 hours unless there is clear clinical evidence for continuation. This will turn antibiotic review on its head, from justifying antibiotic cessation to justifying continuation.
3. 3. Increased ability to challenge inappropriate decisions to escalate or continue antibiotic therapy based on patients’ specific PCT result.
   This will empower pharmacist led AMS ward rounds, targeting those patients with PCT <0.25ng/ml who remain on antibiotics, identifiable through reporting within the electronic prescribing system, to promote appropriate cessation. The impact this will have on antibiotic course lengths is previously described but additionally this will increase the reach of traditionally resource heavy AMS ward rounds, currently limited by capacity of Consultant Medical Microbiologists.

How is the project to be developed in the future?

It is hoped that the demonstrated positive outcomes on antibiotic course lengths, alongside less tangible associated benefit on reduced potentiation of resistant organisms will result in acceptance of the business case to support full rollout of PCT use Trustwide.

The audit of PCT use identified some missed opportunities which have been shared with Lead clinicians in the pilot to enable us to utilise PCT testing to the fullest potential in the future. These included PCT not being undertaken at day 3 but later in antibiotic therapy. This will be mitigated through incorporation of the PCT test as an electronic order that can be selected when completing the electronic antimicrobial stewardship review. Thus clinicians will be prompted to undertake the review and it can be ordered with ‘one click’.

Only a small proportion of the patients reviewed were based on critical care (14%). There is further experience needed in PCT use in this area as testing may be more appropriate at different time intervals and patients may need several tests to identify when infections are resolving and antibiotics can be appropriately stopped.

Should PCT testing be supported Trustwide there will need to be an extensive programme of education, supported in real time on AMS ward rounds, to ensure it is utilised correctly and to its full potential.