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OBJECTIVES: Incorrect labelling of a penicillin allergy can lead to unnecessary use of broad-spectrum, less effective, more harmful, or more costly antibiotics. Community pharmacists are well positioned to educate the public on penicillin allergies, prevent incorrect labelling persisting, and optimize prescribing of antibiotics. This study investigated community pharmacists' capacity to recognize an opportunity to directly de-label a no-risk penicillin allergy. METHODS: A sequential explanatory mixed methods design using mystery shopping (quantitative) and postvisit reflections (qualitative). Mystery shoppers simulated a case of a previously dispensed prescription (involving nonimmune mediated intolerance 'thrush' as the reported allergy) that provided the opportunity for pharmacists to educate on incorrect penicillin allergy. The main outcomes were proportion of community pharmacists who ascertained the nature of the penicillin reaction, provided education on incorrect penicillin allergy labels and its consequences. Knowledge and practices regarding penicillin allergy were collected. KEY FINDINGS: Across two major states in Australia, 265 community pharmacists participated. Only 44.5% (118/265) of pharmacists asked about the nature of the reaction; of those, 91.52% (108/118) indicated that 'thrush' is not an allergic reaction. No pharmacists took the opportunity to educate on how an incorrect allergy label can impact antibiotic prescribing. Postvisit reflection data revealed five probable explanations for the observations viz. outdated knowledge, lack of knowledge, prioritizing management of adverse drug reaction (thrush), variations in duty of care and assumption of true allergy without an assessment. CONCLUSION: Our findings underscore a concerning knowledge and practice gap among community pharmacists regarding penicillin allergy assessment which warrants more support and education in the community pharmacy sector.

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool. METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss' kappa statistics. Assessors' responses and comments were thematically analysed to determine reasons for incorrect classification. RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification w

BACKGROUND: Understanding the trend of global antifungal agent consumption could assist with identification of global healthcare policy inadequacies and promote accessibility and availability of antifungal agents. METHODS: Using pharmaceutical sales data from the IQVIA-multinational integrated data analysis system database, we assessed use of systemic antifungal agents in humans in 27 middle- and 38 high-income countries from 2008 through 2018. RESULTS: Consumption of systemic antifungal agents increased from 0.50 (in 2008) to 0.92 defined daily dose (DDD)/1000 inhabitants/day (in 2018), with a compound annual growth rate of 6.2%. High-income countries remain major consumers of antifungal agents with large variance in quantities consumed, with a gradual decline in consumption in recent years. Consumption in middle-income countries increased. Itraconazole (0.32 DDD/1000 inhabitants/day), terbinafine (0.30 DDD/1000 inhabitants/day), and fluconazole (0.23 DDD/1000 inhabitants/day) were the most commonly used antifungal agents in middle- and high-income countries in 2018. Following incorporation into the World Health Organization Essential Medicines List, itraconazole consumption in middle-income countries surged. Consumption of ketoconazole slowly declined, with 5.04% annual decrease, probably due to labelling changes in 2013 to reflect hepatotoxicity concerns. The use of polyenes (0.004 DDD/1000 inhabitants/day) and echinocandins (0.003 DDD/1000 inhabitants/day) were lowest among all the antifungal drug classes. CONCLUSION: Global consumption of triazoles and terbinafine has gradually increased in middle- and high-income countries. Life-saving antifungal agents, including echinocandins and polyenes, are available only parenterally and may be underutilized, mainly in middle-income countries. Future research on country-specific epidemiology is warranted to guide health policy coordination to ensure equitable access to appropriate use of antifungal agents.

Interprofessional collaboration between general practitioners (GPs) and community pharmacists (CPs) is central to implement antimicrobial stewardship (AMS) programmes in primary care. This study aimed to design a GP/pharmacist antimicrobial stewardship (GPPAS) model for primary care in Australia. An exploratory study design was followed that included seven studies conducted from 2017 to 2021 for the development of the GPPAS model. We generated secondary and primary evidence through a systematic review, a scoping review, a rapid review, nationwide surveys of Australian GPs and CPs including qualitative components, and a pilot study of a GPPAS submodel. All study evidence was synthesised, reviewed, merged, and triangulated to design the prototype GPPAS model using a Systems Engineering Initiative for Patient Safety theoretical framework. The secondary evidence provided effective GPPAS interventions, and the primary evidence identified GP/CP interprofessional issues, challenges, and future needs for implementing GPPAS interventions. The framework of the GPPAS model informed five GPPAS implementation submodels to foster implementation of AMS education program, antimicrobial audits, diagnostic stewardship, delayed prescribing, and routine review of antimicrobial prescriptions, through improved GP-CP collaboration. The GPPAS model could be used globally as a guide for GPs and CPs to collaboratively optimise antimicrobial use in primary care. Implementation studies on the GPPAS model and submodels are required to integrate the GPPAS model into GP/pharmacist interprofessional care models in Australia for improving AMS in routine primary care.

Voriconazole (VCZ) was one of the first mold-active triazoles available; however, its current use among high-risk hematology populations is unknown as the uptake of posaconazole (PCZ) and isavuconazole (ISZ) increases. We evaluated the usage and therapeutic level attainment of VCZ in hematopoietic cell transplantation (HCT) and chimeric antigen receptor T cell (CAR-T) therapy patients at our cancer center. Electronic medical records for all adult HCT or CAR-T patients with an order for VCZ, PCZ, or ISV between January 1, 2018, and June 30, 2020, were extracted. Clinical characteristics, VCZ indication, trough VCZ levels, and frequency of VCZ initiation from 6 months before to 6 months after HCT/CAR-T infusion in consecutive HCT/CAR-T recipients within the study period (infusion between July 1, 2018, and January 1, 2020) were assessed. The association between relevant clinical characteristics and the attainment of subtherapeutic or supratherapeutic levels was also evaluated. Of 468 patients prescribed mold-active triazoles, 256 (54.7%) were prescribed VCZ, 324 (69.2%) PCZ, and 60 (12.8%) ISZ; 152/468 (32.5%) treatment regimens were sequentially modified to alternate mold-active triazoles. Among consecutive HCT and CAR-T recipients at our center, evaluated 6 months pre- or post- HCT/ CAR-T, VCZ was commonly initiated before or after allogeneic HCT (102/381, 26.8%), with most use in the first 30 days after stem cell infusion (40/381, 10.5%); VCZ use was less common in autologous HCT (13/276, 4.7%) and CAR-T (10/153, 6.5%). Of 223 VCZ orders that met inclusion for analysis, indications included empiric treatment in 108/223 (48.4%), directed therapy in 25/223 (11.2%), primary prophylaxis in 69/223 (30.9%) and secondary prophylaxis in 21/223 (9.4%). Of 223 eligible VCZ patients, 144 (64.6%) had at least 1 VCZ level measured during the study period; 75/144 (52.1%) had a therapeutic VCZ level (1.0-5.5 mg/L) at the first measurement (median 2.8mg/L [range 0.1-13.5]) at a med

Abstract Background: Rising antimicrobial resistance (AMR) in primary care is a growing concern and a threat to community health. The rise of AMR can be slowed down if general practitioners (GPs) and community pharmacists (CPs) could work as a team to implement antimicrobial stewardship (AMS) programs for optimal use of antimicrobial(s). However, the evidence supporting a GP pharmacist collaborative AMS implementation model (GPPAS) in primary care remains limited. Aim: With an aim to design a GPPAS model in Australia, this paper outlines how this model will be developed. Methods: This exploratory study undertakes a systematic review, a scoping review, nationwide surveys, and qualitative interviews to design the model. Medical Research Council (MRC) framework and Normalization Process Theory are utilized as guides. Reviews will identify the list of effective GPPAS interventions. Two AMS surveys and paired interviews of GPs and CPs across Australia will explore their convergent and divergent views about the GPPAS interventions, attitudes towards collaboration in AMS and the perceived challenges of implementing GPPAS interventions. Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model and factor analyses will guide the structure of GPPAS model through identifying the determinants of GPPAS uptake. The implementable GPPAS strategies will be selected based on empirical feasibility assessment by AMS stakeholders using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria. Discussion: The GPPAS model might have p

Setting up an interprofessional team for antimicrobial stewardship (AMS) to improve the quality and safety of antimicrobial use in primary care is essential but challenging. This study aimed to investigate the convergent and divergent attitudes and views of general practitioners (GPs) and community pharmacists (CPs) about AMS implementation and their perceived challenges of collaboration to design a GP–pharmacist collaborative AMS (GPPAS) model. Nationwide surveys of GPs and CPs across Australia were conducted January-October 2019. Chi square statistics and a theoretical framework were used for comparative analyses of quantitative and qualitative data, respectively. In total, 999 participants responded to the surveys with 15.4% (n = 386) response rates for GPs and 30.7% (n = 613) for CPs. GPs and CPs were aware about AMS however their interprofessional perceptions varied to the benefits of AMS programs. CPs indicated that they would need AMS training; significantly higher than GPs (GP vs. CP; 46.4% vs. 76.5%; p < 0.0001). GPs’ use of the Therapeutic Guideline Antibiotic was much higher than CPs (83.2% vs. 45.5%; p < 0.0001). No interprofessional difference was found in the very-limited use of patient information leaflets (p < 0.1162) and point-of-care tests (p < 0.7848). While CPs were more willing (p < 0.0001) to collaborate with GPs, both groups were convergent in views that policies that support GP–CP collaboration are needed to implement GPPAS strategies. GP–pharmacist collaborative group meetings (54.9% vs. 82.5%) and antimicrobial audit (46.1% vs. 86.5%) models were inter-professionally supported to optimise antimicrobial therapy, but an attitudinal divergence was significant (p < 0.001). The challenges towards GP–CP collaboration in AMS were identified by both at personal, logistical and organisational environment level. There are opportunities for GP–CP collaboration to improve AMS in Australian p

Abstract Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing ‘big data’ on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years.

BACKGROUND: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated. METHODS: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118). FINDINGS: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group. INTERPRETATION: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects. FUNDING: Research Grants Council, Hong Kong.

Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda.

BACKGROUND: The use of antithymocyte globulin (ATG) in allogeneic hematopoietic cell transplant (HCT) is associated with an increased risk of Epstein-Barr virus (EBV) reactivation and post-transplant lymphoproliferative disorders (PTLD). The dynamics and outcomes of EBV-DNAemia are not well described in this population. METHODS: We retrospectively assessed the kinetics of EBV-DNAemia after ATG conditioning of HCT recipients. Receiver operating characteristic (ROC) curves were used to assess EBV-DNAemia to predict EBV-PTLD in this group. RESULTS: A total of 174/405 (43%) consecutive HCT recipients from two centers met inclusion criteria of ATG conditioned, non-B-cell lymphoma patients. Of these with EBV-DNA measured using standardized IU/ml, 78.6% (92/117) developed EBV-DNAemia: 62% spontaneously resolved; 19% cleared after preemptive rituximab, and 13% developed EBV-PTLD. ROC curve analysis using maximum pre-EBV-PTLD EBV-DNAemia, demonstrated an AUC of 0.912 with EBV-DNAemia of 9782 IU/ml, associated with 82.6% sensitivity and 94.4% specificity for development of EBV-PTLD. Median time for EBV-DNAemia to increase from initial detection to >1000 IU/ml was 7 days; to >10 000 IU/ml, 12 days; and to >100 000 IU/ml, 18 days. Median EBV-DNAemia level prior to administration of rituximab was significantly lower in patients with successful preemptive treatment, compared with those who developed EBV-PTLD (3.41 log10 IU/ml [3.30-3.67] vs. 4.34 log10 IU/ml [3.85-5.13], p = .002; i.e., 2628 IU/ml vs. 21 965 IU/ml, respectively). CONCLUSIONS: EBV-DNAemia >10 000 IU/ml was the strongest predictor of the development of EBV-PTLD, and progression to this level was rapid in ATG-conditioned HCT recipients. This information may guide EBV-PTLD management strategies in these high-risk patients.

BACKGROUND: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT). METHOD: We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre-transplant predictors of CMV reactivation, clinically significant CMV infection (cs-CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized pre-emptive therapy approach to identify at-risk groups to target prevention strategies. RESULTS: Cs-CMVi was most common in D-/R+ unrelated donor transplants (URD). Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56-137 IU/mL, 6% at 138-250 IU/mL and in one patient >250 IU/mL. Median time between the first CMV reactivation (>56 IU/mL) and a viral load >250 IU/mL was 13 days, whereas the time from the first viral load >250 IU/mL to reach a vial load >1000 IU/mL was 4 days. Cs-CMVi was associated with a significant increase in non-relapse mortality (NRM) on multivariate analysis. CONCLUSIONS: Overall, this study indicates that D-/R+ URD recipients are at high-risk for cs-CMVi- and CMV-related mortality, and are potential candidates for targeted CMV prophylaxis. Spontaneous clearance of CMV beyond a viral load of 250 IU/mL is uncommon, suggesting that this could be used as an appropriate threshold to initiate pre-emptive therapy.

Infection-related mortality (IRM) is the most common non-relapse-related cause of death reported after allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies. This report provides the first account of IRM in adults and children undergoing HCT in Australia. Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry database, associated with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death, including infectious etiology and causative organisms, were extracted from the database for adults and children for analysis. At day +100 and 1 year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children, IRM was the leading cause of post-HCT mortality at day +100 at 2.5% and the second highest cause of post-HCT mortality at 1 year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of antithymocyte globulin (ATG) or alemtuzumab, donor-positive/recipient-negative cytomegalovirus (CMV) serostatus, and acute graft-versus-host disease were significant risk factors for IRM. However, in children, age >5 years, acute lymphocytic leukemia as the primary disease, and mismatched unrelated or haploidentical donor source were predictive of IRM. Of the deaths in which an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to post-transplantation lymphoproliferative disorder (PTLD). The most common organisms were Pseudomonas spp, Enterococcus spp, Candida spp, Aspergillus spp, and CMV. In children where an infectious etiology was reported (64%), 13% were attributed to bacteria

Aim To summarise the evidence on pharmacist‐led antifungal stewardship (AFS) programs in the hospital setting and to evaluate their impact on the quality of antifungal prescribing and infection management, antifungal usage and clinical outcomes. Data sources A systematic review of English‐language studies identified in MEDLINE and EMBASE was performed on 27 November 2020 and conducted in accordance with PRISMA. Search terms included ‘antifungal agent’, ‘invasive fungal infection’, ‘antimicrobial stewardship’, ‘patient care bundles’ and ‘pharmacist’. Study selection Eligible studies describing pharmacist‐led quality improvement intervention(s) implemented in the hospital setting targeted at optimising systemic antifungal prescribing. Results Six hundred and forty‐six studies were identified, and seven met inclusion criteria. Five were dedicated to optimising candidaemia management, one at optimising intensive care unit prescribing of caspofungin and one on antifungal prescribing in haematology and oncology units. All studies measured varied metrics relating to quality of prescribing and infection management, reporting improvement in proportion of effective antifungal therapy (n = 1/1), appropriate antifungal selection (n = 1/1), dosing (n = 2/3), management of drug–drug interactions (n = 1/1) and reduced time to antifungal initiation (n = 4/4). Studies that implemented a candidaemia bundle of care reported improvements in composite bundle adherence (n = 2/2), with greatest improvement in ophthalmological consultation (n = 4/4), echocardiography (n = 2/2) and infectious diseases consultation (n = 3/3). There was reduction in antifungal expenditure (n = 4/4) and consumption (n = 2/4). Pharmacist‐led AFS programs did not influence clinical outcomes. Conclusion Available evidence suggests that pharmacist‐led AFS interventions can improve the quality and timeliness of antifungal prescribing and reduce antifungal usage. Further research is required to assess the i

Setting up an interprofessional team for antimicrobial stewardship (AMS) to improve the quality and safety of antimicrobial use in primary care is essential but challenging. This study aimed to investigate the convergent and divergent attitudes and views of general practitioners (GPs) and community pharmacists (CPs) about AMS implementation and their perceived challenges of collaboration to design a GP-pharmacist collaborative AMS (GPPAS) model. Nationwide surveys of GPs and CPs across Australia were conducted January-October 2019. Chi square statistics and a theoretical framework were used for comparative analyses of quantitative and qualitative data, respectively. In total, 999 participants responded to the surveys with 15.4% (n = 386) response rates for GPs and 30.7% (n = 613) for CPs. GPs and CPs were aware about AMS however their interprofessional perceptions varied to the benefits of AMS programs. CPs indicated that they would need AMS training; significantly higher than GPs (GP vs. CP; 46.4% vs. 76.5%; p < 0.0001). GPs' use of the Therapeutic Guideline Antibiotic was much higher than CPs (83.2% vs. 45.5%; p < 0.0001). No interprofessional difference was found in the very-limited use of patient information leaflets (p < 0.1162) and point-of-care tests (p < 0.7848). While CPs were more willing (p < 0.0001) to collaborate with GPs, both groups were convergent in views that policies that support GP-CP collaboration are needed to implement GPPAS strategies. GP-pharmacist collaborative group meetings (54.9% vs. 82.5%) and antimicrobial audit (46.1% vs. 86.5%) models were inter-professionally supported to optimise antimicrobial therapy, but an attitudinal divergence was significant (p < 0.001). The challenges towards GP-CP collaboration in AMS were identified by both at personal, logistical and organisational environment level. There are opportunities for GP-CP collaboration to improve AMS in Australian primary care. However, strengthening GP-pharmacy collaborative

BACKGROUND: Rising antimicrobial resistance (AMR) in primary care is a growing concern and a threat to community health. The rise of AMR can be slowed down if general practitioners (GPs) and community pharmacists (CPs) could work as a team to implement antimicrobial stewardship (AMS) programs for optimal use of antimicrobial(s). However, the evidence supporting a GP pharmacist collaborative AMS implementation model (GPPAS) in primary care remains limited. AIM: With an aim to design a GPPAS model in Australia, this paper outlines how this model will be developed. METHODS: This exploratory study undertakes a systematic review, a scoping review, nationwide surveys, and qualitative interviews to design the model. Medical Research Council (MRC) framework and Normalization Process Theory are utilized as guides. Reviews will identify the list of effective GPPAS interventions. Two AMS surveys and paired interviews of GPs and CPs across Australia will explore their convergent and divergent views about the GPPAS interventions, attitudes towards collaboration in AMS and the perceived challenges of implementing GPPAS interventions. Systems Engineering Initiative for Patient Safety (SEIPS 2.0) model and factor analyses will guide the structure of GPPAS model through identifying the determinants of GPPAS uptake. The implementable GPPAS strategies will be selected based on empirical feasibility assessment by AMS stakeholders using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria. DISCUSSION: The GPPAS model might have potential implications to inform how to better involve GPs and CPs in AMS, and, to improve collaborative services to optimize antimicrobial use and reduce AMR in primary care.

BACKGROUND: Itraconazole (ITZ) is an effective agent when used as primary invasive fungal disease (IFD) prophylaxis, but is limited by drug tolerability and variability in serum concentrations. A new formulation, SUBA-itraconazole (for "super bioavailability"; S-ITZ), addresses the limitations of conventional ITZ formulations. METHODS: We conducted a retrospective cohort study at 2 Australian centers to evaluate the safety, tolerability, and effectiveness of S-ITZ as primary antifungal prophylaxis in hematopoietic cell transplant (HCT) recipients without grade II-IV acute graft-vs-host disease, from day 1 until approximately day 100 (cohort A) or day 1 until neutrophil engraftment (cohort B). A total of 204 patients and 1410 trough plasma ITZ concentrations were assessed. RESULTS: The incidence of breakthrough proven/probable IFD at day 180 was 1.0% (95% confidence interval [CI], .2%-3.2%), with 1.6% in cohort A and 0% in cohort B, and overall fungal-free survival of proven/probable IFD was 82.9% (95% CI, 76.8%-87.4%). Preengraftment early permanent S-ITZ discontinuation was 3.4% overall, with no significant difference between cohorts. No patients required cessation due to gastrointestinal intolerance attributed to S-ITZ. The geometric mean trough plasma ITZ concentration was 1130ng/mL (interquartile range, 566-1801ng/mL; coefficient of variation, 56.57%) and the median time to achieve therapeutic levels was 10 days. CONCLUSIONS: S-ITZ is a safe and well-tolerated oral formulation and is a novel alternative for primary IFD prophylaxis after HCT.

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners’ (GPs’) awareness of AMS, uptake of AMS strategies, attitudes towards GP–pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists’ recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP–pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP–pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP–pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.

Epstein-Barr virus associated post-transplant lymphoproliferative disorders (EBV PTLD) are recognized as a significant cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). The number of patients at risk of developing EBV PTLD is increasing, partly as a result of highly immunosuppressive regimens, including the use of anti-thymocyte globulin (ATG). Importantly, there is heterogeneity in PTLD management strategies between alloHSCT centers worldwide. This review summarizes the different EBV PTLD prevention strategies being utilized including the alloHSCT and T-cell depletion regimes and the risk they confer; monitoring programs, including the timing and analytes used for EBV virus detection, as well as pre-emptive thresholds and therapy with rituximab. In the absence of an institution-specific policy, it is suggested that the optimal pre-emptive strategy in HSCT recipients with T-cell depleting treatments, acute graft vs host disease (GVHD) and a mismatched donor for PTLD prevention is (a) monitoring of EBV DNA post-transplant weekly using plasma or WB as analyte and (b) pre-emptively reducing immune suppression (if possible) at an EBV DNA threshold of >1000 copies/mL (plasma or WB), and treating with rituximab at a threshold of >1000 copies/mL (plasma) or >5000 copies/mL (WB). There is emerging evidence for prophylactic rituximab as a feasible and safe strategy for PTLD, particularly if pre-emptive monitoring is problematic. Future management strategies such as prophylactic EBV specific CTLs have shown promising results and as this procedure becomes less expensive and more accessible, it may become the strategy of choice for EBV PTLD prevention.

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners' (GPs') awareness of AMS, uptake of AMS strategies, attitudes towards GP-pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists' recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP-pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP-pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP-pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care.

Background Behavioural emergencies (BEs) are complex situations in the emergency department (ED) setting. Treatment decisions always must be made within a limited time and are based on incomplete patient data. As a result of the urgency and complexity, patients often are exposed to increased risk of harm. Aim The aim of this paper is to describe the prescribing patterns and adverse events (AEs) associated with parenteral sedation for the management of BEs in Australian EDs. Methods Ten Australian EDs enrolled a convenience sample of adult patients (aged ≥18 years) requiring parenteral sedative medication for BEs. Data were collected prospectively between March 2015 and April 2017 using a designated case report form. Results In all, 564 cases were enrolled in this study. Incomplete cases (n = 17; 3%) were excluded. Of the 547 remaining cases, 63% were male and the median age was 34 years (range 18–95 years). Approximately half the patients (n = 230; 42.1%) required mechanical restraint and parenteral sedation to manage their BEs. Intramuscular monotherapy was administered in most cases (n = 390; 71.3%). The main sedative medications used as monotherapy were droperidol (n = 381; 69.7%), midazolam (n = 54; 9.9%) and olanzapine (n = 26; 4.8%). The most common combination therapy was midazolam + droperidol (n = 36; 6.6%). The incidence of AEs from sedative administration was 13.5%. No deaths or irreversible AEs were reported. Conclusions Overall, the participating EDs provided safe pharmacological management for BEs. AEs following parenteral sedation are common, although serious AEs are rare. Because all patients receiving parenteral sedation for BEs are at risk of AEs, ongoing monitoring of vital signs after parenteral sedation should be a standard protocol in all EDs.

OBJECTIVE: The objective was to describe the incidence, nature, and risk factors for adverse events (AEs) among patients who received parenteral sedation for acute agitation in an emergency department (ED) setting. METHODS: We undertook a prospective observational study and a clinical trial of parenteral sedation for the management of acute agitation. We included agitated adult patients who required parenteral sedation from 2014 to 2017 in 12 Australian EDs, excluding those with incomplete information or aged under 18 years. The primary outcome was the number of patients who experienced at least one AE. Multivariable logistic regression was used to determine factors associated with AEs. RESULTS: A total of 904 patients were included in the analyses (62.3% male; median age = 34 years, range = 18 to 95 years). Of these, 144 (15.9%) patients experienced at least one AE. The most common AEs were oxygen desaturation (7.4%), airway obstruction (3.6%), bradycardia (1.9%), hypotension (1.7%), and prolonged QTc interval (1.3%). No deaths or serious AEs were reported. The following factors had an increased adjusted odds ratio (OR) for experiencing an AE: age 65 years and older (OR = 2.8, 95% confidence interval [CI] = 1.2 to 7.2), more than one type of parenteral sedation administered within 60 minutes (OR = 2.1, 95% CI = 1.4 to 3.1), and alcohol intoxication (OR = 1.8, 95% CI = 1.2 to 2.6). CONCLUSIONS: Sedation-related AEs are common, especially respiratory events. Elderly patients, sedation with multiple sedatives within 60 minutes, and alcohol intoxication increased the risk.

The annual Aged Care National Antimicrobial Prescribing Survey aims to identify local and national prescribing issues and guide antimicrobial stewardship goals In the 2018 point prevalence survey, medication charts of over 20,000 residents were reviewed from 407 participating facilities across Australia On the day of the survey, almost 10% of residents were prescribed an antimicrobial Nearly two-thirds of recently prescribed antimicrobials were for residents who had no documented signs or symptoms of infection Over a quarter of antimicrobials had been prescribed for longer than six months Incomplete documentation was a prominent barrier to proper review of antimicrobial therapy, with the indication, review date or stop date not documented for many prescriptions Recommendations include using appropriate microbiological testing to guide prescribing, following national antimicrobial prescribing guidelines, documenting the indication for the antimicrobial, and its start, stop and review dates, and monitoring and re-evaluating long-term antimicrobial use

BACKGROUND: Clinical studies and mathematical simulation suggest that active surveillance with contact isolation is associated with reduced vancomycin-resistant enterococci (VRE) prevalence compared to passive surveillance. Models using pre- and post-intervention data that account for the imperfect observation and serial dependence of VRE transmission events can better estimate the effectiveness of active surveillance and subsequent contact isolation; however, such analyses have not been performed. METHODS: A mathematical model was fitted to surveillance data collected pre- and post-implementation of active surveillance with contact isolation in the haematology-oncology ward. We developed a Hidden Markov Model to describe undetected and observed VRE colonisation/infection status based on the detection activities in the ward. Bayesian inference was used to estimate transmission rates. The effectiveness of active surveillance was assumed to be via increased detection and subsequent contact isolation of VRE positive patients. RESULTS: We estimated that 31% (95% credible interval: 0.33-85%) of the VRE transmissions were due to cross-transmission between patients. The ratio of transmission rates from patients with contact isolation versus those without contact isolation was 0.33 (95% credible interval: 0.050-1.22). CONCLUSIONS: The majority of the VRE acquisitions in the haematology-oncology ward was estimated to be due to background rates of VRE, rather than within ward patient to patient acquisition. The credible interval for cross-transmission was wide which results in a large degree of uncertainty in the estimates. Factors that could account for background VRE acquisition include endogenous acquisition from antibiotic selection pressure and VRE in the environment. Contact isolation was not significantly associated with reduced VRE transmission in settings where the majority of VRE acquisition was due to background acquisition, emphasising the need to identify and add

BACKGROUND: The combination of midazolam and droperidol has proven superior to droperidol or olanzapine monotherapy in the management of acute agitation in emergency departments (EDs). OBJECTIVE: This is the first economic analysis to evaluate the cost-benefit and cost effectiveness of the midazolam-droperidol combination compared with droperidol or olanzapine for the management of acute agitation in EDs. METHODS: This analysis used data derived from a randomised, controlled, double-blind clinical trial conducted in two metropolitan Australian EDs between October 2014 and August 2015. The economic evaluation was from the perspective of Australian public hospital EDs. The main outcomes included agitation management time and the agitation-free time gained. Sensitivity analyses were undertaken. RESULTS: The midazolam-droperidol combination was the least costly regimen (Australian dollars [AU$]46.25 per patient) compared with the droperidol and olanzapine groups (AU$92.18 and AU$110.45 per patient, respectively). The main cost driver for all groups was the cost of the labour required during the initial adequate sedation. The combination afforded an additional 10-13 min of mean agitation-free time gained, which can be translated to additional savings of AU$31.24-42.60 per patient compared with the droperidol and olanzapine groups. The benefit-cost ratio for the midazolam-droperidol combination was 12.2:1.0, or AU$122,000 in total benefit for every AU$10,000 spent on management of acute agitation. Sensitivity analyses over key variables indicated these results were robust. CONCLUSIONS: The midazolam-droperidol combination may be a cost-saving and dominant cost-effective regimen for the treatment of acute agitation in EDs as it is more effective and less costly than either droperidol or olanzapine monotherapy.

OBJECTIVES: Behavioral emergencies are commonly seen in emergency departments (EDs). Acutely agitated patients can be difficult to manage and sedation may be required to decrease dangerous behavior and to ensure the safety of both the patient and the staff. While the experience of staff caring for this population has been reported, patients' experiences with their overall management remains unknown. We aimed to describe the perceptions and experiences of patients regarding the use of sedation during acute behavioral emergencies. METHODS: Face-to-face semistructured interviews were conducted with adults aged 18 years or older, who had received parenteral sedative medication for the management of a behavioral emergency and were deemed capable to participate. The participants were asked about their experiences of receiving care in the ED during the episode and their perceptions of sedation. All interviews were transcribed verbatim and analyzed thematically. RESULTS: Data saturation was reached after 13 interviews. Two broad themes emerged: trusting relationships and needs or wants following sedation. A trusting relationship is built through 1) confidence in care, 2) sedation as an appropriate treatment, 3) insight into own behavior, and 4) humane treatment. Four subthemes of needs or wants were identified: 1) empathy, 2) debrief, 3) addressing concerns, and 4) follow-up. CONCLUSIONS: A trusting relationship was identified as crucial to minimize the negative impact of coercive measures used to manage behavioral emergencies. Participants expressed similar needs to patients presenting with medical problems. This study illustrates their needs for compassionate communication, adequate information about the treatment provided, and follow-up care.

Background Prolonged voriconazole therapy may be associated with skin squamous cell carcinoma (SCC) in lung transplant (LTx) patients. This is of concern given the frequent use of voriconazole in the LTx setting. The impact of voriconazole therapy on the risk of developing skin SCC in an Australian LTx cohort with additional risk due to high levels of sun exposure remains unclear. Aim This study described the extent and outcomes of new or recurrent skin SCC among LTx patients receiving voriconazole. Methods The present retrospective cohort study was undertaken at The Alfred Hospital, Australia. Adult LTx recipients with skin SCC who had received voriconazole between 1 July 2003 and 30 June 2010 were included. Medical records and histopathology reports were reviewed. Demographics, clinical characteristics, voriconazole exposure (dose and duration), potential risk factors for skin SCC and manifestations of the skin SCC were recorded. The Naranjo algorithm was used to determine the likelihood of skin SCC being due to voriconazole exposure. Results Of the 102 LTx patients receiving voriconazole, 14 (13.7%) had at least one episode of skin SCC: seven (Group 1) had skin SCC during or after voriconazole exposure; three (Group 2) had skin SCC before commencing voriconazole therapy, which recurred or worsened subsequently; three (Group 3) had a history of skin SCC prior to voriconazole being prescribed but no skin SCC was noted during or after voriconazole exposure; and one (Group 4) had multiple skin SCCs before LTx and voriconazole use, and developed further skin SCC post voriconazole. The median (interquartile range) of voriconazole exposure in Group 1, 2 and 3 patients was 119 days (79.5, 693), 1127 days (665.5, 1129) and 173 days (135.5, 341), respectively. The Naranjo score indicated a probable association between voriconazole use and skin SCC in three patients and a possible relationship in eight. Conclusions Prolonged voriconazole exposure may contribute to

AIM: To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation. DESIGN AND SETTING: A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015. PARTICIPANTS: Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients. INTERVENTION AND COMPARATOR: Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively. MEASUREMENTS: The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated. FINDINGS: The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation. CONCLUSION: A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone.

BACKGROUND: There are limited published data on the types and appropriateness of oral and intravenous (IV) antibiotics prescribed to patients receiving haemodialysis. This information is critical to optimise antibiotic prescribing. Therefore this study aims to describe the patterns of use and the appropriateness of oral and IV antibiotics prescribed to patients receiving haemodialysis. METHODS: This was a prospective, observational study across four community and two hospital inpatient haemodialysis units in Melbourne, Australia. Data were collected from July 2014 to January 2015 from participants. Antibiotic regimens prescribed were compared with nationally available antibiotic guidelines and then classified as being either appropriate, inappropriate or not assessable by an expert multidisciplinary team using the National Antimicrobial Prescribing Survey tool. RESULTS: Overall, 114 participants consented to this study where 55.3% (63/114) received antibiotics and 235 antibiotic regimens were prescribed at a rate of 69.1 antibiotic regimens/100 patient-months. The most common oral antibiotics prescribed were amoxycillin/clavulanic acid and cephalexin. The most common IV antibiotics prescribed were vancomycin, piperacillin/tazobactam, cephazolin and ceftriaxone. The percentage of inappropriate antibiotic regimens prescribed were 34.9% (15/43) in the community setting and 22.1% (40/181) in the hospital setting. Furthermore, 29.4% (30/102) of oral and 20.5% (25/122) of IV antibiotic regimens were inappropriate with incorrect dosing as the primary reason. CONCLUSION: Although this study is limited by the sample size, it describes the high antibiotic exposure that patients receiving haemodialysis experience. Of concern is inappropriate dose and frequency being a major issue. This requires interventions focused on the quality use of medicines and antimicrobial stewardship aspects of prescribing in this population.

The efficacy of infection control interventions against Acinetobacter baumannii remains unclear, despite such information being critical for effective prevention of the transmission of this pathogen. Mathematical modeling offers an alternative to clinical trials, which may be prohibitively expensive, unfeasible or unethical, in predicting the impact of interventions. Furthermore, it allows the ability to ask key "what if" questions to evaluate which interventions have the most impact. We constructed a transmission dynamic model to quantify the effects of interventions on reducing A. baumannii prevalence and the basic reproduction ratio (R0) in intensive care units (ICUs). We distinguished between colonization and infection, and incorporated antibiotic exposure and transmission from free-living bacteria in the environment. Under the assumptions and parameterization in our model, 25% and 18% of patients are colonized and infected with A. baumannii, respectively; and R0 is 1.4. Improved compliance with hand hygiene (≥87%), enhanced environmental cleaning, reduced length of ICU stay of colonized patients (≤ 10 days), shorter durations of antibiotic treatment of A. baumannii (≤6 days), and isolation of infected patients combined with cleaning of isolation rooms are effective, reducing R0 to below unity. In contrast, expediting the recovery of the intestinal microbiota (e.g. use of probiotics) is not effective. This study represents a biologically realistic model of the transmission dynamics of A. baumannii, and the most comprehensive analysis of the effectiveness of interventions against this pathogen. Our study provides important data for designing effective infection control interventions.

Little is known about the transmission dynamics of Acinetobacter baumannii in hospitals, despite such information being critical for designing effective infection control measures. In the absence of comprehensive epidemiological data, mathematical modelling is an attractive approach to understanding transmission process. The statistical challenge in estimating transmission parameters from infection data arises from the fact that most patients are colonised asymptomatically and therefore the transmission process is not fully observed. Hidden Markov models (HMMs) can overcome this problem. We developed a continuous-time structured HMM to characterise the transmission dynamics, and to quantify the relative importance of different acquisition sources of A. baumannii in intensive care units (ICUs) in three hospitals in Melbourne, Australia. The hidden states were the total number of patients colonised with A. baumannii (both detected and undetected). The model input was monthly incidence data of the number of detected colonised patients (observations). A Bayesian framework with Markov chain Monte Carlo algorithm was used for parameter estimations. We estimated that 96-98% of acquisition in Hospital 1 and 3 was due to cross-transmission between patients; whereas most colonisation in Hospital 2 was due to other sources (sporadic acquisition). On average, it takes 20 and 31 days for each susceptible individual in Hospital 1 and Hospital 3 to become colonised as a result of cross-transmission, respectively; whereas it takes 17 days to observe one new colonisation from sporadic acquisition in Hospital 2. The basic reproduction ratio (R0) for Hospital 1, 2 and 3 was 1.5, 0.02 and 1.6, respectively. Our study is the first to characterise the transmission dynamics of A. baumannii using mathematical modelling. We showed that HMMs can be applied to sparse hospital infection data to estimate transmission parameters despite unobserved events and imperfect detection of the organism.

BACKGROUND: Multidrug-resistant (MDR) organisms have been increasingly reported at hospital admission. Recognising the magnitude, trend and predictors for MDR organisms in community-onset bloodstream infections (COBSI) is crucial for guiding empiric antibiotic prescribing. METHODS: Positive blood culture isolates recovered from patients presenting to the emergency department during a ten-year period (1st Jan 2002-31st Dec 2011) were assessed. Trend analyses of MDR organisms were performed. Risk factors for COBSI caused by an MDR organism and predictors for 30-day mortality were also determined. RESULTS: A total of 1721 positive blood culture isolates were identified during the study period with a yearly incidence of 30-43 isolates/10 000 ED presentations. The proportion of MDR Escherichia coli causing COBSI increased from 9%-26% (P < 0.001), whilst methicillin-resistant Staphylococcus aureus remained at high levels (20%-30%). A total of 360 patients were included in a matched case-control (1:1) study, and residents in long-term care facilities (adjusted odds ratio [AOR], 4.9 [95% CI, 2.1-11.6]), home wound care (AOR, 5.5 [95% CI, 1.6-18.7]), underlying immunosuppression (AOR, 3.5 [95% CI, 1.6-7.7]), recent surgery (AOR, 3.5 [95% CI, 1.1-11.6]), and exposure to antibiotics within 3 months (AOR, 5.5 [95% CI, 2.8-10.6]) were independently associated with MDR COBSI. High risk source of COBSI, age and Pitt bacteraemia score were independent predictors for 30-day mortality. CONCLUSIONS: A concerning trend in MDR organisms causing bloodstream infection from the community is occurring. Risk factors for MDR organisms have been identified to assist in empiric antibiotic prescribing for those presenting to hospital with sepsis.

BACKGROUND: Enterococci are a major cause of healthcare-associated infection. In Australia, vanB vancomycin-resistant enterococci (VRE) is the predominant genotype. There are limited data on the factors linked to vanB VRE bacteraemia. This study aimed to identify factors associated with vanB VRE bacteraemia, and compare them with those for vancomycin-susceptible enterococci (VSE) bacteraemia. METHODS: A case-case-control study was performed in two tertiary public hospitals in Victoria, Australia. VRE and VSE bacteraemia cases were compared with controls without evidence of enterococcal bacteraemia, but may have had infections due to other pathogens. RESULTS: All VRE isolates had vanB genotype. Factors associated with vanB VRE bacteraemia were urinary catheter use within the last 30 days (OR 2.86, 95% CI 1.09-7.53), an increase in duration of metronidazole therapy (OR 1.65, 95% CI 1.17-2.33), and a higher Chronic Disease Score specific for VRE (OR 1.70, 95% CI 1.05-2.77). Factors linked to VSE bacteraemia were a history of gastrointestinal disease (OR 2.29, 95% CI 1.05-4.99) and an increase in duration of metronidazole therapy (OR 1.23, 95% CI 1.02-1.48). Admission into the haematology/oncology unit was associated with lower odds of VSE bacteraemia (OR 0.08, 95% CI 0.01-0.74). CONCLUSIONS: This is the largest case-case-control study involving vanB VRE bacteraemia. Factors associated with the development of vanB VRE bacteraemia were different to those of VSE bacteraemia.

Clinical researchers in acute emergency settings are commonly faced with the difficulty of satisfying the conventional ethical requirement of obtaining informed consent, whilst ensuring a representative group of patients is recruited into studies. We discuss our own experience in addressing institutional ethical requirements to obtain informed consent in a multi-centre trial, recruiting highly agitated patients in the emergency setting in Melbourne, Australia. We suggest that, through the application of existing ethical and legal frameworks and pre-emptive communication with the key stakeholders in ethics committees, hospital insurers and legal representatives, a balance can be struck between ethical and legal requirements on the one hand, and the integrity of the research question, on the other.