Since first identified in late 2019, the acute respiratory syndrome coronavirus (SARS-CoV2) and the resulting coronavirus disease (COVID-19) pandemic has overwhelmed healthcare systems worldwide, often diverting key resources in a bid to meet unprecedented challenges. To measure its impact on national antimicrobial stewardship (AMS) activities, a questionnaire was designed and disseminated to antimicrobialstewardship leads in the United Kingdom (UK). Most respondents reported a reduction in AMS activity with 64% (61/95) reporting that COVID-19 had a negative impact on routine AMS activities. Activities reported to have been negatively affected by the pandemic include audit, quality improvement initiatives, education, AMS meetings, and multidisciplinary working including ward rounds. However, positive outcomes were also identified, with technology being increasingly used as a tool to facilitate stewardship, e.g., virtual meetings and ward rounds and increased the acceptance of using procalcitonin tests to distinguish between viral and bacterial infections. The COVID-19 pandemic has had a significant impact on the AMS activities undertaken across the UK. The long-term impact of the reduced AMS activities on incidence of AMR are not yet known. The legacy of innovation, use of technology, and increased collaboration from the pandemic could strengthen AMS in the post-pandemic era and presents opportunities for further development of AMS.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug–drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. ‘Breakthrough’ invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3–4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one ‘probable’ and one ‘possible’. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.

Introduction The United Kingdom Clinical Pharmacist Association Pharmacy Infection Network (UKCPA PIN) is the community of pharmacy professionals with an interest or specialism in infection management. As we come out of the Covid-19 pandemic, it is important for the leadership of UKCPA PIN to understand the current need and wishes of the community. Aim This study aimed to explore infection specialist pharmacy professionals about their research activity, experience, and perceived barriers to greater research activity. Methods An online, anonymised survey, consisting of closed and free-type open questions, was circulated to UKCPA PIN members for completion in September and October 2021 using the Google Forms platform. The questionnaire was developed and piloted amongst members of UKCPA PIN committee to identify current research activity and barriers. Responses were downloaded and underwent descriptive analysis with Microsoft Excel. This work was deemed a service evaluation and therefore did not require ethics approval. Results There were 38 responses were received from pharmacists in all 7 NHS England regions, Scotland, and Wales (6% of UKCPA PIN forum members). Pharmacy technicians were invited to participate but none did so. 13 (34%) described themselves as being actively involved in research, 13 (34%) described themselves as having done research in the past, 8 (21%) described themselves as not having the opportunity to develop research capabilities. 27 (71%) respondents had completed a postgraduate diploma, 8 (21%) had completed MSc or equivalent, 6 (16%) had completed a PhD or equivalent, 11 (29%) were Good Clinical Practice accredited and 10 (26%) had undertaken local research training. 6 (16%) were consultant pharmacists or accredited by the Royal Pharmaceutical Society as being consultant-ready, 10 (27%) were building a consultant portfolio and 15 (39%) were aspiring to build a consultant portfolio in the future. Of the 28% that were building a consultant portfolio, 6 were confident that they were already meeting the research outcomes and 4 were not. Antimicrobial pharmacists were most frequently wanting to undertake research in the areas of antimicrobial stewardship (11, 29%), antifungal stewardship (5, 13%) and allergies/penicillin delabelling (5, 13%). The greatest barriers identified were lack of time/funding (27, 71% agreed significant barrier), lack of funding for costs of undertaking research (17, 45%), lack of support with research methods (9, 24%) and lack of support with dissemination of research (9, 24%). A number of potential support options were proposed to respondents, with “Signposting resources to help you write research protocols” and “A repository of in progress antimicrobial research in the UK” being the most popular (19 and 17 respondents, respectively, described as very useful). Discussion/Conclusion There is a significant interest in research amongst antimicrobial pharmacists and scope for enhancing the contribution of pharmacists to research around antimicrobials and infectious disease. A limitation of this study was the small sample size; however, the themes provide important information for UKCPA PIN to provide support for its members.

Introduction Vancomycin treats serious Gram-positive infections such as methicillin-resistant Staphylococcus aureus. In St George’s University Hospital’s (SGH) intensive care unit (ICU) settings, vancomycin is administered by continuous infusion. Steady-state serum concentrations are measured daily with a 20-25 mg/L target. Non-therapeutic concentrations are associated with adverse drug reactions/prolonged length of stay.1 A SGH service-evaluation conducted across all three ICUs, revealed variable adherence to/effectiveness of its vancomycin prescribing/administration/monitoring protocol.2 Consequently, multifaceted interventions were devised using the Institute-for-Healthcare-Improvement’s model Plan-Do-Study-Act (PDSA) cycles and piloted on General ICU (GICU). Aim (1) To improve adherence to/effectiveness of the vancomycin protocol. (2) To ascertain administration accuracy of paper-fluid-balance-charts compared to the electronic-prescribing-and-medicines-administration (ePMA) system to assist with identifying per protocol treated patients. Methods PDSA Cycle-1 was conducted over a 9-month period (09/2021-05/2021) in which a mix of system/person-focused interventions were implemented. Protocol dosing2 was revised, introducing a >90kg patient 2g loading dose, renal-function category revision and increased maintenance dose for creatinine clearance (CLCR) >90ml/min. Protocol accessibility was increased via integration into an ePMA prescribing interface, plus CliniBee/Microguide apps. Educational slides on relevant protocol aspects were incorporated into medical/nursing induction training. Data relating to vancomycin prescribing/administration/monitoring for all non-renal replacement patients was extracted retrospectively from the ePMA system between 09/2021-05/2022. This data was compared to baseline GICU data (07/2020-07/2021).2 The project and associated interventions were approved by Trust Clinical Governance and Audit Teams. Data was collected by pharmacists directly involved in patient’s care and stored/analysed on the Trust’s secure server in line with Data Protection Act principles. Due to local generalisability, ethics approval wasn’t required. Results Compared to baseline, the proportion of patients receiving per protocol prescribing/administration of loading/maintenance doses with daily monitoring, nearly doubled (39% (7/18) to 68% (15/22)). 48-hour vancomycin serum concentrations in all patients increased therapeutically by 21% (3/9 to 7/13). In per protocol treated patients, concentrations increased 15% (2/7 to 4/9) therapeutically, decreased 21% (3/7 to 2/9) supra-therapeutically and increased 4% (2/7 to 3/9) sub-therapeutically. Supra-therapeutic concentrations were associated with CLCR<50ml/min. Sub-therapeutic concentrations were associated with CLCR>90ml/min and obesity. Compared to the ePMA system, there was 36% (8/22) less paper-fluid-balance-charts recording both loading/maintenance doses. Maintenance dose administration times in 9% (2/22) of cases differed by >60 minutes. Discussion/Conclusion Staff-turnover periods were associated with decreased protocol compliance. Observations suggest further education is required around prescribing/administration of standardised infusion bags for maintenance dosing. Pharmacist integration into daily Microbiology ward rounds may increase protocol compliance. Higher 20mg/kg loading doses for obese patients and maintenance dose revision should be considered to reduce non-therapeutic concentrations.3 Limitations include heterogenous/small sample sizes due to data paucity and vancomycin requirement. This can be addressed by involving all ICU’s in PDSA Cycle-2. Due to disparities, both the ePMA system and paper-fluid-balance-charts should be used to identify protocol adherence. Utilisation of digital-infusion-pump data to quantify administration accuracy may offer a promising solution. Piloted multifaceted interventions were successful at improving adherence to/effectiveness of the vancomycin protocol. Findings have informed further interventions and data capture methods for PDSA Cycle-2 implementation across all ICUs. References 1. Perin N, Roger C, Marin G, Molinari N, Evrard A, Lavigne J et al. Vancomycin Serum Concentration after 48 h of Administration: A 3-Years Survey in an Intensive Care Unit. Antibiotics. 2020;9(11):793. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698174/ 2. Oakley R, Bakrania P, Yau T, Standing J, Lonsdale D. P37 Variable adherence to and effectiveness of a vancomycin continuous infusion protocol within ICUs at a London tertiary-care hospital: a single-centre retrospective service evaluation. JAC-Antimicrobial Resistance. 2022;4(Supplement_1). Available from: https://academic.oup.com/jacamr/issue/4/Supplement_1 3. Rybak M, Le J, Lodise T, Levine D, Bradley J, Liu C et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020;77(11):835-864. Available from: https://academic.oup.com/ajhp/article/77/11/835/5810200?login=false

Background COVID-19-associated pulmonary aspergillosis (CAPA) is a recognized but incompletely characterized secondary fungal infection reported to be associated with increased mortality in patients in the ICU. Case definitions have been published but lack clarity: clinical and radiological features are non-specific and rely heavily on mycological tests for which both a timely availability and accuracy pose an issue contributing to the wide range of incidence reported of 4%–34%. In April 2021, we introduced a CAPA guideline for ICU patients at St George's University Hospital including when to suspect and how to investigate for CAPA (see Figure 1). The aim of this study was to evaluate its utility in identifying patients meeting ECMM_ISHAM criteria for possible/probable CAPA. Methods Between March 2020 and May 2021 a retrospective audit was completed that identified all PCR-confirmed COVID-19 ICU patients prescribed either voriconazole, caspofungin, anidulafungin and AmBisome and reviewed their medical records, imaging and microbiology results categorizing patients into proven, probable, possible or unlikely CAPA based on ECMM/ISHAM criteria. Results Twenty-one patients were prescribed the specified antifungals. All had CT imaging and varying microbiological investigations. Real-time clinical decisions on empirical antifungal prescribing for CAPA (start or stop) were made by a multidisciplinary team (MDT) comprising Microbiology and ICU physicians in light of clinical, microbiology and radiology findings. Nine of 21 patients prescribed empirical antifungals had radiological evidence of CAPA. Aspergillus fumigatus was cultured in six patients from bronchoalveolar lavage and two patients from sputum/trachea. Of these, seven were deemed significant and one attributed to colonization. Two patients were diagnosed with ‘probable’ and five as ‘possible’ CAPA, of whom one died. All seven patients received antifungal treatment for CAPA of varying duration (range 18–49 days). Only one patient had an underlying host risk factor (B cell lymphoma). Of those defined with probable/possible CAPA, average time from intubation to treatment was 18.4 days (range 8–31) and from onset of COVID symptoms to treatment was 28.5 days (range 18–49). Three of 21 patients were treated empirically for CAPA and all 3 died prior to further investigation and 15 patients following an MDT were felt to have unlikely CAPA. Serum BDG and GM were negative in all patients with probable/possible CAPA. Conclusions The St George's CAPA guideline would have picked up two out of seven cases; two cases had antifungals started in another hospital so the utility of this guideline could not be assessed. Based on analysis of these cases the following changes were made to the guideline: (i) to assess patients ≥8 days post ICU admission (rather than ≥10 days) and (ii) assess patients following ≥3 days post appropriate antibiotic therapy (rather than following ≥5 days). Serum BDG and GM were negative in all patients with probable/possible CAPA prior to starting treatment therefore negative serum markers do not exclude diagnosis; this is consistent with experience reported elsewhere. Radiological presentations of CAPA were variable and wide ranging, and BAL sampling was not always possible, therefore we found the MDT approach including radiology, infection, respiratory and ICU invaluable in making decisions regarding treatment. This helped to reduce the use of fungal diagnostics, antifungal agents and appropriately manage patients with potential CAPA. The rationalization of antifungal use by the introduction of this guidelines was particularly important and also expedited the introduction of in-house fungal diagnostics.