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Evolving medicines stewardship programs - learnings from antimicrobial stewardship
Bettina Kirk, Quality Pharmacist - Antimicrobial Stewardship, Quality & Medication Safety Unit
World Antimicrobial Resistance (AMR) Awareness Week (WAAW) is an annual global campaign to improve awareness and understanding of AMR, encourage antimicrobial stewardship (AMS) best practices, and to help stop further emergence and spread of AMR.
AMS programs began in the late 1990’s, they became a mandatory component of national hospital accreditation standards in 2012, and are now well embedded in hospitals across Australia. Learnings from successes with these programs has seen stewardship fundamentals expanded to other therapeutic focus areas.
Medication stewardship generally refers to coordinated strategies and interventions to optimise use as well as minimise harm, both for individuals and society, usually within a specific therapeutic area where there is a high risk of inappropriate prescribing or adverse outcomes.
Various strategies include supporting safety and quality systems, interventions and tools that guide and optimise practice.
AMS is a proven approach to improving the quality of medicine use. Other areas developing stewardship programs emulating AMS initiatives include antifungals, opioids, and anticoagulants, which are discussed further in this special edition of CIRCUIT.
Mould the future: practice good Antifungal Stewardship
Anna Reardon, Cancer Care Pharmacist –Icon Cancer Centre North Lakes
Antifungal Stewardship (AFS) refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents, in order to achieve the best clinical outcomes and minimise the risk of resistance and adverse effects. The principles of antifungal stewardship parallel those of established antimicrobial stewardship (AMS) programs.1 AFS has emerged as a critical component in the battle against fungal infections, especially within highrisk populations of patients undergoing oncology and haematology treatment.
Invasive fungal infections (IFI) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFIs is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug-drug interactions and the emergence of antifungal resistance.2 Figure 1 highlights the timeline of antifungal drug development, and the associated emergence of antifungal resistance; despite this trend, new antifungals in the development pipeline remain limited.3,4
Polyenes
• Ampho B: Amphotericin B
• L-AMB: Liposomal amphotericin B
Ampho B
Flucytosine
Ketoconazole
Fluconazole
L-AMB
Itraconazole
Caspofungin
Voriconazole
Micafungin
Posaconazole
Anidulafungin
Isavuconazole
Source: Miller, R.A. A Case for Antifungal Stewardship. Curr Fungal Infect Rep 12, 33–43 (2018).
Ketoconazole treatment failures
Aspergillus resistance to itraconazole reports of fluconazole resistance in Candida infections
FKS mutations identified in echinocandin-resistant Candida
Aspergillus resistance to voriconazole in agriculture
Clinical isolates of voriconazoleresistant Aspergillus fumigatus
Clinical identification of Candida auris breakthrough mould infections with azole exposure
Figure 1: Antifungal drug development and emergence of antifungal resistance isolates3,4
The
growing concern and the role of Antifungal Stewardship
In oncology and haematology, where patients are often treated with aggressive therapies, such as chemotherapy and haematopoietic stem cell transplantation (HSCT), the risk of IFIs is particularly high. These patient populations are disproportionately affected by IFIs and are the largest consumers of antifungal agents, both in terms of prophylaxis and treatment within hospitals.5 From six studies evaluating the appropriateness of antifungal prescribing, either solely or predominantly in the cancer setting, the overall rate of appropriate antifungal prescribing was found to be suboptimal, ranging between 29.4% and 56.5%.2 As the population at risk of IFIs continues to grow due to the increased burden of cancer, the need for hospitals to establish AFS programs and measures to monitor and prevent infection has become increasingly important.2 Consensus guidelines for antifungal stewardship, surveillance and infection prevention were published in 20212 to outline the essential components, key interventions and metrics, which can help guide implementation of an
Essential components and key interventions of an AFS program2
• Incorporate AFS as a component of AMS
• Establish a multidisciplinary team to oversee a quality improvement program to optimise antifungal prescribing and IFI management in hospitals with high systemic antifungal use
• Adapt IFI management guidelines and bundles of care to the local context and integrate into the workflow of prescribers
• Target educational efforts at departments with the highest number of antifungal prescriptions and repeat at least once a year to increase understanding and knowledge of appropriate drug selection, dosing, therapeutic drug monitoring (TDM) and fungal diagnostics
• Where prescribing restrictions are implemented, offer interventions such as post-prescription review and feedback (PPRF), including therapeutic advice, as a conjunctive measure
• Adopt PPRF as a core AFS intervention
• Involve personnel with expertise in the area of fungal diagnostics (e.g. microbiologists, infectious disease clinicians) in AFS programs, such that appropriate diagnostic testing is adequately promoted
• Provide access to timely TDM for antifungal agents in hospitals managing patients at risk of IFI
• Audit antifungal prescribing and IFI management and utilise data to drive quality improvement
Antifungal stewardship and pharmacy
Pharmacists can play a vital role in the AFS multidisciplinary team to ensure antifungal usage is restricted to patients that require prophylaxis or treatment of IFI and to minimise impact of antifungal resistance. As part of their clinical practice, pharmacists are well placed to be involved with:4
• Prescription review for discontinuing unrequired therapy
• De-escalating (e.g. from broad to narrow spectrum) where appropriate
• Prompting a switch from the intravenous to oral route when suitable
• Optimising drug therapy
• Monitoring, which should comprise:
– Ensuring appropriate dosing
– Pharmacokinetic/pharmacodynamic interaction management
– Therapeutic drug monitoring (TDM): individualisation of dosage by maintaining blood drug concentrations within a target range
– Dose adjustments in hepatic and renal dysfunction
– Allergy status review
• Optimising non-drug treatment, such as source control
• Patient education
Pharmacists can also play an essential role in educating other healthcare professionals on AFS, local and national resistance patterns and awareness of new IFIs and appropriate treatments. As a member of the multidisciplinary team they are instrumental in developing and implementing evidence-based antifungal guidance and in encouraging appropriate prescribing.4 One useful resource to help with clinical practice, as well as clinical education for other healthcare professionals, is “Introduction to the updated Australasian consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting, 2021”.5 This contains useful information on optimising antifungal drug delivery and monitoring, antifungal prophylaxis, diagnosis and management of various types of fungal infections, as well as key patient information for healthcare workers caring for patients with or at risk of IFIs.
Antifungal stewardship is a vital component of infection control, especially in oncology and haematology settings, focusing on appropriate therapy, resistance prevention and minimising adverse effects, in turn improving patients’ outcomes and combating the rise of resistant fungal pathogens.
References available on request
Managing pain, minimising risk: a stewardship approach to opioid use in acute pain
Karlee Del Pra, Clinical Pharmacist, Slade Pharmacy Warragul
Opioid use and potential harms
Opioids are important in the management of acute pain; however, associated risks need to be considered when prescribing.1-4
Every day in Australia, opioids cause2,5,6 150 hospitalisations 3 deaths
Over the past decade, the rate of opioid-induced deaths from pharmaceutical opioids has been higher than from illegal opioids and most opioid hospitalisations are the result of adverse effects from the intended use of prescription opioids.7 Persistent postoperative opioid use is of particular concern and a risk factor for dependence; 4-11% of opioid-naïve Australians are still taking opioids 2-4 months after surgery and more than a third of Australian adults on long-term opioids had their first prescription from their surgeon.4,6
A focus on acute pain management
Opioid stewardship involves ensuring the safe and appropriate use of opioids.2,4,6 For an opioid-naïve patient with acute pain, it supports use of immediate-release forms at the lowest appropriate dose and for the shortest duration.2-4 Opioid stewardship doesn’t always mean the reduction of opioids but rather the tailoring and optimisation, and may include strategies such as:
• Multimodal analgesia to decrease the amount and duration of opioids required.2-4,6
• Avoid slow-release formulations as they have no benefit in acute pain, cannot be rapidly adjusted, and carry an increased risk of opioid-induced ventilatory impairment.2-4,6
• Limit the duration of opioids prescribed, as this directly impacts patient consumption postoperatively.2-4,6 The risk of misuse increases by 20% with each additional week of opioid use.4 Opioid requirements in the 24 hours prior to discharge should be considered.
• Educate patients on the safe storage and disposal of opioids 2-4,6 Between 40-94% of opioids dispensed postoperatively are not used and 90% of patients don’t dispose of excess opioids, leading to a pool of opioids in the community.4,6
• Discuss and document an opioid weaning and cessation plan with the patient and ensure it is communicated at transitions of care.2-4,6
Pain has traditionally been measured using self-reported severity scales (e.g. the Numeric Rating Scale) but these are associated with the unrealistic expectation to be pain free and have not demonstrated improved pain treatment or outcome.8 The Functional Activity Score, particularly in conjunction with pain scores, is a better approach to guiding pain management.3,4,8,9 Pain should be managed sufficiently for patients to participate in their recovery and safely carry out functional goals, rather than aiming to be free from pain.3,4 Our choice of words is also important. Phrases such as ‘pain killers’ perpetuates the idea that we are aiming for no pain and instead words such as ‘pain reliever’ or ‘medicines that manage pain’ should be used, and can further improve patient pain communication.
Opioid analgesics are highrisk medicines, widely used in hospitals and the community to manage pain.2 Stewardship of opioid analgesics through co-ordinated interventions can help to optimise their use for managing acute pain and reduce the possibility of opioidrelated harm.
References available on request
Venous Thromboembolism (VTE) Stewardship
Justine Forbes, Clinical Pharmacist, Slade Pharmacy Hollywood
Why is the Stewardship of VTE Prevention Important?
Venous thromboembolism (VTE) including deep vein thrombosis and pulmonary embolism affects over 10 million people each year, globally.1 Estimates suggest it accounts for 7% of deaths annually in Australian hospitals and is a major contributor to morbidity and mortality, and adequate VTE prevention has been shown to reduce the incidence of VTE by around 70%.2 Despite these numbers, many at risk patients in Australia do not receive recommended prevention according to evidence-based guidelines.2 VTE stewardship programs aim to optimise the use of VTE prophylaxis and reduce the associated costs and risks.
VTE Prevention Framework
It is the duty of all healthcare professionals to embrace VTE stewardship, the goal being to ensure that all hospitalised patients are assessed for VTE risk in a timely manner, using a verified risk assessment tool endorsed by the hospital, and that patients are informed and share in decisions regarding their VTE prevention plan (Figure 1).2,3 Results should be documented on the patient’s medication chart or medical progress notes.2,3
VTE prophylaxis must be considered for each patient, with respect to their individual comorbidities and medications. Many factors that increase the risk of VTE are commonly related to a patient’s reason for admission e.g. surgery, stroke, heart failure, and hospitalisation itself is a major risk factor.2,3
However, patient factors unrelated to admission can further increase VTE risk, such as obesity.
Patients with a BMI of 30 or above are at increased risk of VTE.2,4 Health professionals should be aware that standard doses of low molecular weight heparins (LMWH) may not be sufficient in those with BMI above 40, and should seek specialist advice or refer to locally endorsed guidelines.4,5
Figure 1: Seven steps to help reduce the risk of blood clots during and following a hospital stay2
1
2
3
4
5
6
Timely assessment of clotting risk
Prevention planning, balancing the risk of clotting against bleeding
Education and informed decision making
Documentation and communication of the clot-prevention plan
Appropriate clotprevention methods
Reassessment of risk and monitoring for clotrelated complications
7 Post discharge care planning
VTE in Cancer Patients
VTE risk is also elevated in malignancy, with cancer patients making up ~20% of all VTE cases.6,7 Risk varies according to cancer type, and treatment or prophylaxis needs to balance future VTE events with bleed risk.
A timely VTE risk assessment should be performed, and pharmacological prophylaxis with LMWH used where indicated in hospitalised cancer patients.7 The Australian Commission’s VTE Prevention Clinical Care Standard recommends VTE reassessment at intervals no longer than every 7 days for hospitalised non-cancer patients, but during cancer treatment, bloods can change daily and platelet levels can fall, increasing the risk of bleeding; continuous reassessment of risk is essential for these patients.2 VTE risk is even higher in multiple myeloma (MM) patients as the treatment for this disease also increases risk.6 Thalidomide, lenalidomide and pomalidomide, common treatments for MM, increase the risk of thrombosis, especially in combination with highdose steroids used in chemotherapy. Aspirin or LMWH are given to these patients to help combat the risk. 6-8 The use of direct-acting oral anticoagulants (DOACs) as VTE prophylaxis in MM is currently an area of research. Data is still uncertain.6-8
VTE is one of the leading preventable causes of death in hospitals, and costs the Australian healthcare system $1.72 billion annually.2 VTE stewardship can substantially help reduce the risk to hospitalised patients, and VTE prevention methods are ranked as the top intervention hospitals can make to improve patient safety.2 All healthcare professionals can undertake the role of steward in their everyday practice to improve outcomes for patients.
References available on request
If you have any queries regarding Circuit content and authors please contact your pharmacy manager. Every effort has been made to ensure this newsletter is free from error or omission. sladepharmacy.com.au