Antimicrobial prescribing in referral hospitals in Timor-Leste: results of the first two national point prevalence surveys, 2020-21.

Objectives: To describe antimicrobial use (AMU) in patients admitted to hospitals in Timor-Leste. Methods: In 2020 and 2021, we undertook antimicrobial prescribing point prevalence surveys across all six hospitals in Timor-Leste (one national and five municipal) to describe AMU and appropriateness in admitted patients. Results: In 2020, 291/394 (73.9%) surveyed patients had been prescribed antimicrobials, compared with 260/403 (64.5%) in 2021 (P = 0.004). Most (309/551; 56.1%) were prescribed one antimicrobial, and 179/551 (32.5%) were prescribed two. The most commonly prescribed antibiotics were ceftriaxone (38.5% in 2020, 41.5% in 2021) and ampicillin (35.7% in 2020, 32.3% in 2021), followed by gentamicin, metronidazole and cloxacillin. Reserve antibiotics like meropenem and vancomycin were minimally used. Of all antimicrobial prescriptions, 70.8% were deemed appropriate in 2020 and 69.1% in 2021. Antimicrobial prescriptions for surgical and post-partum prophylaxis were frequently deemed inappropriate [37/50 (74.0%) and 39/44 (88.6%) prescriptions, respectively]. Conclusions: Most patients admitted to hospital in Timor-Leste are prescribed antimicrobials, and approximately one-third of these prescriptions are inappropriate. However, this was in the context of limited local guideline availability at the time of surveys and limited microbiological culture capacity outside of the capital, Dili. Improved microbiological guidance, iterative guideline revisions based on local antimicrobial resistance (AMR) surveillance data, and enhanced stewardship activities including further point prevalence studies, could improve antimicrobial use, optimize patient outcomes and reduce AMR in Timor-Leste.

Is Education Alone Enough to Sustain Improvements of Antimicrobial Stewardship in General Practice in Australia? Results of an Intervention Follow-Up Study.

Sustained behaviour change and practice improvements for the optimal use of antimicrobials remains challenging in primary care. In 2018, a simple antimicrobial stewardship education programme involving guideline recommendations for common infections, antimicrobial audit reports, and local antibiograms resulted in significant improvements in guideline compliance and more appropriate antimicrobial prescribing by GPs. This observational follow-up study aims to examine the sustainability of the positive intervention effect after two years of implementation of the intervention. Practice-based data on all oral antimicrobial prescriptions issued by GPs were collected retrospectively to compare with intervention data and to measure the sustainability of the intervention effect. The data were analysed using a two-sample test of proportions. The primary outcomes included changes in the rate of prescription compliance with the Australian "Therapeutic Guidelines: Antibiotic" and the appropriateness of antimicrobial choice and duration of therapy. Overall, there was a significant decline in guideline compliance, from 58.5 to 36.5% (risk ratio (RR) (95% CI): 0.62 (0.52-0.74)), in the appropriateness of antimicrobial choice, from 92.8 to 72.8% (0.78 (0.73, 0.84)), and in the prescribed duration, from 87.7 to 53.3% (0.61 (0.54, 0.68)) in the intervention follow-up period. In respiratory infections and ear, nose, and throat infections, the rates of guideline compliance and appropriate choice and duration of antimicrobial prescription decreased significantly at p < 0.001. Appropriateness in the duration of antimicrobial therapy also significantly decreased for most antimicrobials. The evidence suggests that a simple and single-occasion antimicrobial stewardship education programme is probably not enough to sustain improvements in the optimal use of antimicrobials by GPs. Future research is needed to validate the results in multiple GP clinics and to examine the effect of sustained education programmes involving infection-specific and antimicrobial-targeted audits and feedback.

Improving diagnostic antimicrobial stewardship in respiratory tract infections: a protocol for a scoping review investigating point-of-care testing programmes in community pharmacy.

INTRODUCTION: Diagnostic uncertainty regarding the cause of respiratory tract infections (RTIs) multiplies the problem of unnecessary use of antibiotics and antimicrobial resistance in primary care. Point-of-care testing (POCT) programmes have been recognised as a potential stewardship strategy to optimise antimicrobial use in primary care. There is a need for greater understanding of community pharmacy-based POCT programmes in reducing the unnecessary use of antimicrobials in patients with RTIs. This review systematically maps out evidence around the effectiveness, feasibility and implementation challenges of POCT programmes in community pharmacy to improve safe antimicrobial use in RTIs. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist and the Arksey and O'Malley methodology framework will guide the reporting of this review. We will systematically review studies with either randomised controlled trial, non-randomised controlled trial, before-after study, observational study or pilot feasibility study design. Medline, Emcare, PubMed, Health Technology Assessment, Cochrane Central Register of Controlled Trials and Google Scholar databases will be used to search for articles. Three reviewers will independently screen, review and select studies with POCT programmes involving community pharmacists for antimicrobial stewardship in RTIs. Summary statistics and random effects model, if data permit, will be used to summarise the effectiveness, feasibility and cost-effectiveness of the POCT programme. The Consolidated Framework for Implementation Research will capture POCT implementation drivers. ETHICS AND DISSEMINATION: This review study does not require research ethics approval. Findings will be disseminated through national and international conferences, seminars and publication in a peer-reviewed journal.

A Novel GPPAS Model: Guiding the Implementation of Antimicrobial Stewardship in Primary Care Utilising Collaboration between General Practitioners and Community Pharmacists.

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.

A systems thinking approach for antimicrobial stewardship in primary care.

INTRODUCTION: The establishment of antimicrobial stewardship (AMS) in primary care is central to substantially reduce the antimicrobial use and the associated risk of resistance. This perspective piece highlights the importance of systems thinking to set up and facilitate AMS programs in primary care. AREAS COVERED: The challenges that primary care faces to incorporate AMS programmes is multifactorial: an implementation framework, relevant resources, team composition, and system structures remain under-researched, and these issues are often overlooked and/or neglected in most parts of the world. Progress in the field remains slow in developed countries but potentially limited in low- and middle-income countries. EXPERT OPINION: The key AMS strategies to optimize antimicrobial use in primary care are increasingly known; however, health system components that impact effective implementation of AMS programs remain unclear. We highlight the importance of systems thinking to identify and understand the resource arrangements, system structures, dynamic system behaviors, and intra- and interprofessional connections to optimally design and implement AMS programs in primary care. An AMS systems thinking systemigram (i.e. a visual representation of overall architecture of a system) could be a useful tool to foster AMS implementation in primary care.

Antimicrobial stewardship in Australia: the role of qualitative research in programme development.

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.

Development of an antimicrobial stewardship implementation model involving collaboration between general practitioners and pharmacists: GPPAS study in Australian primary care.

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.

Divergent and Convergent Attitudes and Views of General Practitioners and Community Pharmacists to Collaboratively Implement Antimicrobial Stewardship Programs in Australia: A Nationwide Study.

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 system structure and practice agreements is a priority to improve interprofessional trust, competencies, and communications for AMS and to establish a GPPAS model in future.

Antimicrobial stewardship by Australian community pharmacists: Uptake, collaboration, challenges, and needs.

OBJECTIVE: To assess community pharmacists' (CPs') awareness and uptake of evidence-based antimicrobial stewardship (AMS) strategies, attitudes toward collaboration with general practitioners (GPs), and needs to improve AMS practices. METHODS: A nationwide survey of randomly sampled community pharmacies across Australia was conducted in April-October 2019. RESULTS: The response rate of CPs was 30.7% (613 of 2000) and 592 participating CPs (96.5%) described the key barriers to and facilitators of improving AMS. CPs (447 of 613, 72.9%) were familiar with AMS but felt that they would require training (468 of 612, 76.5%) and access to AMS practice guidelines (566 of 605, 93.6%). Respondents perceived that AMS programs could reduce the inappropriate use of antimicrobials (409 of 612, 66.8%) and the costs of treating infection (508 of 612, 83.0%). CPs often counseled patients (591 of 609, 97.0%) and reviewed drug interactions or allergies (569 of 607, 93.8%) before dispensing antimicrobials. Respondents less often used the national Therapeutic Guidelines: Antibiotic (274 of 602, 45.5%) or assessed guideline-compliance of prescribed antimicrobials (231 of 609, 37.9%). CPs were less likely to communicate with GPs (254 of 609, 41.8%) when an antimicrobial prescription was believed to be suboptimal and perceived that GPs are not receptive to their intervention regarding the antimicrobial choice (500 of 606, 82.6%) and dosage (416 of 606, 68.6%). Point-of-care tests (114 of 596, 19.1%) and patient information leaflets (149 of 608, 24.5%) were used uncommonly. Most respondents supported policies that could foster GP-pharmacist collaboration (560 of 606, 92.4%), limit accessibility of selected antimicrobials (420 of 604, 74.4%), and reduce repeat-dispensing of antimicrobial prescriptions (448 of 604, 74.2%). CPs faced interpersonal, interactional, structural, and resource-level barriers to collaborate with GPs for practicing AMS. CONCLUSIONS: CPs are aware of the importance of sensible use of antimicrobials but have had limited training and resources to conduct AMS activities. Improving GPs' receptiveness and system structures for increased GP-CP collaboration seem to be a priority to accelerate CP-led AMS implementation. Further study is required to understand the views of stakeholders about the feasibility of implementing evidence-based GP-CP collaborative AMS approaches.

A Nationwide Survey of Australian General Practitioners on Antimicrobial Stewardship: Awareness, Uptake, Collaboration with Pharmacists and Improvement Strategies.

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.

Knowledge, Perceptions and Practices of Community Pharmacists Towards Antimicrobial Stewardship: A Systematic Scoping Review.

The scope of antimicrobial stewardship (AMS) surveys on community pharmacists (CPs) is uncertain. This study examines the breadth and quality of AMS survey tools measuring the stewardship knowledge, perceptions and practices (KPP) of CPs and analyse survey outcomes. Following PRISMA-ScR checklist and Arksey and O'Malley's methodological framework seven medical databases were searched. Two reviewers independently screened the literatures, assessed quality of surveys and KPP outcomes were analysed and described. Ten surveys were identified that assessed CPs' AMS perceptions (n = 7) and practices (n = 8) but none that assessed AMS knowledge. Three survey tools had been formally validated. Most CPs perceived that AMS improved patient care (median 86.0%, IQR, 83.3-93.5%, n = 6), and reduced inappropriate antibiotic use (84.0%, IQR, 83-85%, n = 2). CPs collaborated with prescribers for infection control (54.7%, IQR 34.8-63.2%, n = 4) and for uncertain antibiotic treatment (77.0%, IQR 55.2-77.8%, n = 5). CPs educated patients (53.0%, IQR, 43.2-67.4%, n = 5) and screened guideline-compliance of antimicrobial prescriptions (47.5%, IQR, 25.2-58.3%, n = 3). Guidelines, training, interactions with prescribers, and reimbursement models were major barriers to CP-led AMS implementation. A limited number of validated survey tools are available to assess AMS perceptions and practices of CPs. AMS survey tools require further development to assess stewardship knowledge, stewardship targets, and implementation by CPs.

Effectiveness of interventions involving pharmacists on antibiotic prescribing by general practitioners: a systematic review and meta-analysis.

BACKGROUND: The use of community antibiotic stewardship programmes (ASPs) is rising; however, their effectiveness when pharmacists are involved is uncertain. OBJECTIVES: To assess the effectiveness of ASPs involving pharmacists at improving antibiotic prescribing by general practitioners (GPs). METHODS: Medline, Embase, Emcare, PubMed, PsycINFO, Cochrane CENTRAL, CINAHL Plus and Web of Science databases were searched to February 2018. Randomized and non-randomized studies of ASPs involving pharmacists as interventionists to GPs were included. Primary outcomes were absolute changes in GPs' antibiotic prescribing rate (APR) and antibiotic prescribing adherence rate (APAR) according to recommendations/guidelines. Meta-analysis used random effects models. RESULTS: Fifteen studies reporting 18 trials were included in the meta-analysis: 8 assessed the APR and 10 the APAR. APR reductions (OR 0.86, 95% CI 0.78-0.95, moderate-certainty evidence) and APAR improvements (OR 1.96, 95% CI 1.56-2.45, high-certainty evidence) were observed at 6 months median intervention follow-up. High-quality randomized trials reduced the APR (OR 0.92, 95% CI 0.90-0.94) and increased the APAR (OR 2.55, 95% CI 2.16-3.01). Interventions were successful in decreasing the APR (OR 0.93, 95% CI 0.90-0.95) and increasing the APAR (OR 1.72, 95% CI 1.04-2.84) when implemented by a pharmacist-GP team. Interventions involving pharmacist-infectious disease professional teams also decreased the APR (OR 0.81, 95% CI 0.66-1.0) and increased the APAR (OR 2.36, 95% CI 1.87-2.96). GP education plus prescribing feedback, and group meetings were effective in both outcomes, whereas GP education, academic detailing and workshop training were effective in APAR outcome. However, substantial heterogeneity was demonstrated. CONCLUSIONS: ASPs involving pharmacists are effective in decreasing antibiotic prescribing and increasing guideline-adherent antibiotic prescribing by GPs.

Improving antibiotic prescribing by general practitioners: a protocol for a systematic review of interventions involving pharmacists.

INTRODUCTION: Effective antibiotic options in general practice for patients with infections are declining significantly due to antibiotic over-prescribing and emerging antibiotic resistance. To better improve antibiotic prescribing by general practitioner (GP), pharmacist-GP collaborations have been promoted under antibiotic stewardship programmes. However, there is insufficient information about whether and how pharmacists help GPs to more appropriately prescribe antibiotics. This systematic review aims to determine whether pharmacist-led or pharmacist-involved interventions are effective at improving antibiotic prescribing by GPs. METHODS AND ANALYSIS: A systematic review of English language randomised controlled trials (RCTs), cluster RCTs, controlled before-and-after studies and interrupted time series studies cited in MEDLINE, EMBASE, EMCARE, CINAHL Plus, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials and Web of Science databases will be conducted. Studies will be included if a pharmacist is involved as the intervention provider and GPs are the intervention recipients in general practice setting. Data extraction and management will be conducted using Effective Practice and Organisation of Care data abstraction tools and a template for intervention description and replication. The Cochrane and ROBINS-I risk of bias assessment tools will be used to assess the methodological quality of studies. Primary outcome measures include changes (overall, broad spectrum and guidelines concordance) of GP-prescribed antibiotics. Secondary outcomes include quality of antibiotic prescribing, delayed antibiotic use, acceptability and feasibility of interventions. Meta-analysis for combined effect and forest plots, χ2 test and I2 statistics for detailed heterogeneity and sensitivity analysis will be performed if data permit. Grading of Recommendations Assessment, Development and Evaluation and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidance will be used to report findings. ETHICS AND DISSEMINATION: No ethics approval is required as no primary, personal or confidential data are being collected in this study. The findings will be disseminated to national and international scientific sessions and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017078478.

The effect of temperature on mortality in rural Bangladesh--a population-based time-series study.

BACKGROUND: Studies in urban cities have consistently shown evidence of increased mortality in association with hot and cold weather. However, few studies have examined temperature-mortality relationship in the rural areas of developing countries. In this study we therefore aimed to characterize the daily temperature-mortality relationships in rural Bangladesh. METHODS: A generalized linear Poisson regression model was used to regress a time-series of daily mortality for all-cause and selected causes against temperature, controlling for seasonal and interannual variations, day of week and public holidays. A total of 13 270 all-cause deaths excluding external causes for residents under demographic surveillance in Matlab, Bangladesh were available between January 1994 and December 2002. RESULTS: There was a marked increase in all-cause deaths and deaths due to cardiovascular, respiratory and perinatal causes at low temperatures over a lag of 0-13 days. Every 1 degrees C decrease in mean temperature was associated with a 3.2% (95% CI 0.9-5.5) increase in all-cause mortality. However, there was no clear heat effect on all-cause mortality for any of the lags examined. CONCLUSIONS: This study found that daily mortality increased with low temperatures in the preceding weeks, while there was no association found between high temperatures and daily mortality in rural Bangladesh. Preventive measures during low temperatures should be considered especially for young infants.