Surveillance of Antimicrobial Use in Long-Term Care Facilities: An Antimicrobial Mapping Survey.

OBJECTIVES: To explore antimicrobial management processes in Australian residential aged care facilities (RACFs), including antimicrobial prescribing, supply, administration, and documentation to inform surveillance activities. DESIGN: Voluntary, online cross-sectional survey. SETTING AND PARTICIPANTS: The survey was disseminated to all South Australian RACFs (n = 237) seeking participation from an infection prevention and control lead (preferred respondent), a nurse or senior RACF staff member, or an aged care pharmacist. METHODS: The survey was open during May-June 2023. Questions aimed to understand clinical and medication management systems, sources of antimicrobial prescription and supply, management by external health care providers and documentation of antimicrobial administration. A process map of antimicrobial management in RACFs was developed. RESULTS: Of the 54 RACFs included in the analysis (29.5% response rate), most used an electronic clinical documentation system (74.1%) or a hybrid electronic paper-based system (22.2%). Medication charts were either electronic (81.0%), hybrid (5.6%), or paper-based (13.0%). Antimicrobials were prescribed by the resident's usual general practitioner, but also by locums, hospital or specialist physicians, nurse practitioners, virtual care physicians, and dentists. Oral, topical, and inhaled antimicrobial formulations were usually supplied by community pharmacies, and intravenous formulations were predominately supplied by hospitals for administration by outreach nurses. Almost all RACFs (96.2%) had imprest stock of antimicrobials that included both oral and intravenous formulations. Antimicrobials were predominately administered by an enrolled nurse or a registered nurse. CONCLUSIONS AND IMPLICATIONS: Antimicrobial management in RACFs is complex, particularly during care transitions. Multiple prescribers and sources of antimicrobials, use of different systems for clinical documentation, particularly by external health care providers, and clinical governance relating to imprest supplies were identified as key areas where medication management could be improved. Addressing these gaps will facilitate comprehensive, real-time antimicrobial surveillance in Australian RACFs.

Modelling the Future Clinical and Economic Burden of Antimicrobial Resistance: The Feasibility and Value of Models to Inform Policy.

Due to the increasing threat to public health and the economy, governments internationally are interested in models to estimate the future clinical and economic burden of antimicrobial resistance (AMR) and to evaluate the cost-effectiveness of interventions to prevent or control resistance and to inform resource-allocation decision making. A widely cited UK report estimated that 10 million additional deaths will occur globally per annum due to AMR by 2050; however, the utility and accuracy of this prediction has been challenged. The precision of models predicting the future economic burden of AMR is dependent upon the accuracy of predicting future resistance rates. This paper reviews the feasibility and value of modelling to inform policy and resource allocation to manage and curb AMR. Here we describe methods used to estimate future resistance in published burden-of-disease models; the sources of uncertainty are highlighted, which could potentially mislead policy decision-making. While broad assumptions can be made regarding some predictable factors contributing to future resistance rates, the unexpected emergence, establishment and spread of new resistance genes introduces substantial uncertainty into estimates of future economic burden, and in models evaluating the effectiveness of interventions or policies to address AMR. Existing reporting standards for best practice in modelling should be adapted to guide the reporting of AMR economic models, to ensure model transparency and validation for interpretation by policymakers.

Comparative analysis of Australian hospital antimicrobial utilization, using the WHO AWaRe classification system and the adapted Australian Priority Antimicrobial List (PAL).

BACKGROUND: In 2020 the Australian Priority Antibacterial List (PAL) was developed to support national surveillance of antibacterial usage. OBJECTIVES: To compare the WHO AwaRe classification system with the Australian PAL to analyse antibacterial utilization in Australian acute care hospitals. METHODS: Monthly antibacterial usage rates (defined daily dose per 1000 occupied bed days) were calculated using pharmacy dispensing records together with patient occupancy data for all acute care hospitals contributing to the National Antimicrobial Utilisation Surveillance Program for 2015-19. Annual usage rates as a proportion were determined using the WHO AWaRe and Australian PAL categorization systems. RESULTS: In 2019, 70.0% of total-hospital aggregate antibacterial use in Australian acute-care hospitals fell into the WHO Access category, with 29.4% of usage in Watch and 0.6% in the Reserve category. Analysis using the PAL classification system showed 40.1% of hospital usage fell into the Access category, 55.6% in Curb and 3.8% in the Contain categories. On average, cefazolin usage comprised 12.5% of acute hospital usage. CONCLUSIONS: Cefazolin, a first-line agent for surgical prophylaxis in Australia, was identified as a key antibacterial driving the differing results seen between the two classification systems. Data on the proportions of day surgery relative to inpatient surgical cases would assist the accuracy of benchmarking usage between hospitals using the PAL categorization system. The use of a targeted, nationally approved prioritized classification system can provide a focus for antimicrobial stewardship at a national level, however a clear understanding of the consumption metric used, as well as its limitations, are required for interpretation.

Value assessment of antimicrobials and the implications for development, access, and funding of effective treatments: Australian stakeholder perspective.

BACKGROUND: The frameworks used by Health Technology Assessment (HTA) agencies for value assessment of medicines aim to optimize healthcare resource allocation. However, they may not be effective at capturing the value of antimicrobial drugs. OBJECTIVES: To analyze stakeholder perceptions regarding how antimicrobials are assessed for value for reimbursement purposes and how the Australian HTA framework accommodates the unique attributes of antimicrobials in cost-effectiveness evaluation. METHODS: Eighteen individuals representing the pharmaceutical industry or policy-makers were interviewed. Interviews were transcribed verbatim, coded, and thematically analyzed. RESULTS: Key emergent themes were that reimbursement decision-making should consider the antibiotic spectrum when assessing value, risk of shortages, the impact of procurement processes on low-priced comparators, and the need for methodological transparency when antimicrobials are incorporated into the economic evaluation of other treatments. CONCLUSIONS: Participants agreed that the current HTA framework for antimicrobial value assessment is inadequate to properly inform funding decisions, as the contemporary definition of cost-effectiveness fails to explicitly incorporate the risk of future resistance. Policy-makers were uncertain about how to incorporate future resistance into economic evaluations without a systematic method to capture costs avoided due to good stewardship. Lacking financial reward for the benefits of narrower-spectrum antimicrobials, companies will likely focus on developing broad-spectrum agents with wider potential use. The perceived risks of shortages have influenced the funding of generic antimicrobials in Australia, with policy-makers suggesting a willingness to pay more for assured supply. Although antibiotics often underpin the effectiveness of other medicines, it is unclear how this is incorporated into economic models.

Estimating the utilisation of unregistered antimicrobials in Australia.

OBJECTIVE: To identify and estimate the usage of unregistered antimicrobial drugs in Australian clinical practice. METHODS: A descriptive pharmaco-epidemiological study, utilising three data sources: analysis of Special Access Scheme (SAS) applications for unregistered antimicrobials included in clinical guidelines over a five year period, analysis of antimicrobials dispensed from South Australian public hospital pharmacy departments over a two year period and analysis of National Antimicrobial Utilisation Surveillance Program (NAUSP) data for reported inpatient usage of unregistered antimicrobials in Australian hospitals over the last 5 years. RESULTS: 59 unregistered antimicrobials were identified using the mixed methods. 18,362 Special Access Scheme applications were submitted between May 2012 and April 2017 to access the 20 unregistered antimicrobials identified in the Therapeutic Guidelines® (eTG complete); 51.4% were determined by the prescriber to be for life-threatening indications. Annual applications more than doubled over the five years. 34 unregistered antimicrobials were dispensed from South Australian public hospitals between July 2015 and June 2017. On average, 1.1% of total antimicrobial usage (Defined Daily Doses) per month was accessed via the SAS, of which 87.7% were for outpatients or discharged patients. 34 unregistered antimicrobials for systemic use identified in the NAUSP database were used in Australian hospitals between 2013 and 2018. CONCLUSION: The use of unregistered antimicrobials in Australian clinical practice is not uncommon. With increasing antimicrobial resistance, there will be a continued reliance on older less-used antimicrobial agents and an increasing need for novel drugs, therefore regulatory pathways need to facilitate security of supply and assurance of medicine quality and safety.

Feasibility of de-linking reimbursement of antimicrobials from sales: the Australian perspective as a qualitative case study.

BACKGROUND: There is a disparity in the economic return achievable for antimicrobials compared with other drugs because of the need for stewardship. This has led to a decline in pharmaceutical companies' willingness to invest in the development of these drugs and a consequent global interest in funding models where reimbursement is de-linked from sales. OBJECTIVES: To explore the perspective of stakeholders regarding the feasibility of de-linked reimbursement of antimicrobials in Australia. METHODS: Semi-structured interviews were conducted with 18 participants sourced from the pharmaceutical industry and individuals representing public-sector payers or regulators. Interviews were transcribed verbatim, coded and thematically analysed using the framework method. RESULTS: Five key themes were identified in the interviews: funding silos are a barrier to de-linking reimbursement; varying levels of supporting evidence are (currently) required for funding depending upon setting; funding status or cost is used as a stewardship tool; a de-linked model may cost more; and concerns regarding governance and access to antimicrobials exist in the private sector. CONCLUSIONS: Australia's current multi-tiered funding of medicines across different levels of government was perceived as a barrier to de-linked reimbursement. Participants felt that the responsibility for antimicrobial funding and stewardship should be integrated and centralized. Implementing a nationally funded de-linked reimbursement model for new antimicrobials would require a review of funding decision-making criteria, given that most MDR infections are off-label indications and could not then be funded through the Australian Pharmaceutical Benefits Scheme. Findings from this study could be applicable to other countries with reimbursement frameworks similar to Australia.

Clinical indications treated with unregistered antimicrobials: regulatory challenges of antimicrobial resistance and access to effective treatment for patients.

Objective Increasing antimicrobial resistance and a concurrent paucity of new antimicrobials marketed increases the risk that patients will develop infections resistant to currently available drugs. This study aimed to determine the range of clinical indications for which unregistered antimicrobials are prescribed at two tertiary hospitals in South Australia to identify any trends over a 2-year period. The effects of recent regulatory changes to the Special Access Scheme (SAS) were assessed. Methods Data were extracted from application forms submitted to the Therapeutic Goods Administration to access unregistered antimicrobials via the SAS pathway at two Australian tertiary hospitals for the period July 2015-June 2017. Average weighted antimicrobial prices were retrieved from the hospital iPharmacy (DXC Technology, Macquarie Park, NSW, Australia) dispensing system. To estimate the effect of a new access pathway (Category C), the SAS classification for each application was retrospectively assessed over time with each regulatory change. Results Between July 2015 and June 2017, 477 SAS applications for 29 different antimicrobials were submitted for 353 patients at the two hospitals. The most common indications were tuberculosis (43.6%) and refractory Helicobacter pylori (10%). Regulatory changes reduced the proportion of applications requiring preapproval for access. Conclusions Although the introduction of a new pathway has decreased the administrative burden when accessing unregistered antimicrobials, this study highlights the range of clinical conditions for which there are no registered drugs available in Australia. What is known about the topic? With increasing antimicrobial resistance and a paucity of novel antimicrobials entering the market, access to older, previously less-used antimicrobials is increasingly important in clinical practice. Accessing unregistered antimicrobials is common practice in Australian hospitals, but the range of clinical indications for which they are used is unclear. What does this paper add? Increasing antimicrobial resistance and a concurrent paucity of new antimicrobials being marketed globally is increasing the risk that patients may develop infections that cannot be treated with registered products. This study describes the range of clinical conditions for which registered antimicrobials are not available or appropriate, illustrating the challenges associated with sustainable access to effective treatments. What are the implications for practitioners? Access to effective antimicrobials in a timely manner is essential for optimal patient outcomes. Reliance on unregistered products is associated with increased risks regarding timely access to safe, quality-assured, effective medicines.

Infliximab for ipilimumab-induced colitis: A series of 13 patients.

OBJECTIVE: To review the outcomes of metastatic melanoma patients treated with infliximab for severe steroid-refractory colitis secondary to ipilimumab therapy. BACKGROUND: Immune-related colitis is a known potential adverse effect of ipilimumab, that causes significant morbidity and extended hospital stays. There are limited outcome data for patients treated with infliximab for ipilimumab-induced colitis refractory to corticosteroids. Management guidelines have been developed based on case study evidence only. DESIGN AND SETTING: A retrospective review of all patients administered infliximab for ipilimumab-induced colitis at South Australian public hospitals between October 2011 and April 2015. MAIN OUTCOME MEASURES: Resolution of colitis/diarrhea, duration of hospital stay, dosage regimen of infliximab used (single dose vs multiple dose) and surgical intervention if required. RESULTS: Between October 2011 and April 2015, 106 patients were dispensed ipilimumab from South Australian public hospitals for the treatment of metastatic melanoma. Thirteen were administered infliximab for severe, steroid-refractory colitis secondary to ipilimumab. Sixty-two percent received a single dose of infliximab only. Four patients achieved resolution of colitis symptoms at 1 month postinfliximab. Thirty-three percent required surgical intervention despite treatment with infliximab. One patient declined surgery and subsequently died due to bowel perforation. The average number of overnight bed days due to colitis was 27. CONCLUSION: This series of patients with severe ipilimumab-induced colitis suggests that despite treatment with infliximab a high proportion of patients do not achieve resolution of symptoms. Review of these cases has highlighted the absence of evidence-based guidelines to treat severe, steroid refractory colitis secondary to ipilimumab. Further prospective studies may clarify the role of infliximab for the treatment of ipilimumab-induced colitis.