July 2015
clinical initiatives, research and current updates in treatment
The need for an Antimicrobial Stewardship Program Anthony Fico, Epic Pharmacy Murdoch
The risk of a return to the ‘pre-antibiotic’ era Up to 50% of antimicrobial regimens prescribed in Australian hospitals are considered inappropriate.1 Inappropriate use of antimicrobials contributes to the emergence of resistant bacteria and infections with multi-resistant bacteria, a risk of patient harm from avoidable adverse reactions and interactions with other drugs and unnecessary costs. Of greatest concern is the increasing emergence of antimicrobial resistance (AMR) which the World Health Organisation rates as a global health security threat requiring a concerted cross-sectional action by governments and society as a whole.1 No major new types of antibiotics have been developed in the last thirty years and the lack of new agents along with increasing AMR could return society to the ‘pre-antibiotic’ era where we are unable to treat certain infections.
Antimicrobial Stewardship An Antimicrobial Stewardship (AMS) program is the combination of a range of strategies and interventions designed to improve and measure the appropriate use of antimicrobials by promoting the selection of the optimal antimicrobial drug, dose, duration of therapy and route of administration, with the aim of improving patient safety and quality
of care. Comprehensive and successful AMS programs have been shown to:2 ¬ ¬ Reduce inappropriate antimicrobial use (by 22% to 36%) ¬ ¬ Improve patient outcomes ¬ ¬ Reduce antimicrobial resistance ¬ ¬ Reduce healthcare costs National Safety and Quality Health Service (NSQHS) Standard 3: Preventing and Controlling Healthcare Associated Infections, includes the requirement that an AMS program is in place as a core criterion (3.14) for hospital accreditation. Other specific actions required to achieve criterion 3.14 are: ¬ ¬ The clinical workforce prescribing antimicrobials have access to current endorsed therapeutic guidelines on antibiotic usage ¬ ¬ Monitoring antimicrobial usage and resistance is undertaken ¬ ¬ Action is taken to improve the effectiveness of AMS The success of AMS depends on the explicit support of the hospital administration, the allocation of adequate resources and the cooperation and engagement of prescribers.2 Multidisciplinary teams help implement the kind of improvements and changes required for effective AMS. The involvement of both an Infectious Disease (ID) physician (and/or microbiologist)
and a pharmacist (with ID training, if possible) as core team members is considered essential to effective programs. Where an onsite ID physician or a clinical microbiologist is not available, the AMS team should be led by an interested clinician with a clinical pharmacist and they should seek external support for AMS activities.2,4
Strategies for implementing AMS Five strategies are considered essential for effective AMS in Australia. They are:2 ¬¬ Implementing clinical guidelines that are consistent with the latest version of Therapeutic Guidelines: Antibiotic (current version 15 – released November 2014), and which take into account local microbiology and antimicrobial susceptibility patterns. ¬¬ Establishing formulary restrictions and approval systems that include restricting broad-spectrum and later generation antimicrobials to patients in whom their use is clinically justified. Types of restriction mechanisms recommended include:5 –– Expert approval: require a nominated expert (e.g. ID physician) to have input or involvement in the prescribing of the antimicrobial agent –– Criteria-based: outline specific conditions that must be met for an antimicrobial prescription to be automatically approved
Timeline of antibiotic development 1 Over the last 30 years, no major new types of antibiotics have been developed 1910
1920
1930
1940
1950
1960
1970
1980
1990
2000
2010
Discovery void Penicillin
Cephalosporin
If a restrictive formulary is not feasible, persuasive interventions such as dissemination of educational resources, reminders, audit and feedback about how antimicrobials are prescribed, may be beneficial in the long term.3 Antimicrobial restrictions may be categorised using a ‘traffic light system’ which is considered to be a successful tool for educating prescribers about local formulary restrictions. Red — Highly restricted Orange — Restricted Green — Unrestricted ¬¬ Reviewing antimicrobial prescribing with intervention and direct feedback to the prescriber — this should, at a minimum, include intensive care patients. ¬¬ Monitoring performance of antimicrobial prescribing by collecting and reporting unit or ward-specific use data, auditing antimicrobial use and using quality use of medicines indicators. Programs available include: –– National Antimicrobial Prescribing Survey which provides a snapshot of antimicrobial prescribing. Users can engage in annual benchmarking audits and site specific audits. –– National Antimicrobial Utilisation Surveillance Program provides contributing hospitals with bimonthly
Carbapenem
and annual reports on their antibiotic usage rates, enabling them to compare their usage to similarly peered hospitals and thus identify areas for improvement. ¬ ¬ Ensuring the clinical microbiology laboratory uses selective reporting of susceptibility testing results that is consistent with hospital antimicrobial treatment guidelines.
Everyone’s responsibility All healthcare practitioners can assist in addressing AMR. Seven actions that can be undertaken now to aid improved AMS:5 1. Obtain cultures before starting therapy where possible (N.B. collections should not delay empiric antibiotic therapy if required). 2. Ensure the latest Therapeutic Guidelines: Antibiotic is available in all clinical areas. Any locally endorsed guidelines take into account recommendations in the Therapeutic Guidelines and also reflect local antimicrobial susceptibilities. 3. Document indication and review date. This enables timely review by the team if required and reminds clinicians to review care. 4. Review antimicrobial therapy at 48-hours. Convert to targeted therapy when the pathogen and its susceptibilities are known.
Fluoroquinolones
5. Consider IV to oral switch where appropriate. 6. Seek advice for complex cases from clinical microbiology or ID physician. 7. Educate consumers about antibiotic use.
Act now AMS is mandatory for the accreditation of Australian hospitals and hospitals administrators are advised to implement and maintain AMS programs. Antibiotics are a limited resource with AMR being a real, current and worldwide problem restricting our treatment options. If we don’t all take action today, there may be no cure tomorrow. Please contact your EPIC Pharmacy Manager to discuss the resources we can provide to assist in establishing and maintaining an effective AMS program. Tools for the implementation and ongoing support of AMS can be found at: ¬¬ Clinical Excellence Commission: http://www.cec.health.nsw.gov.au/ programs/quah ¬¬ Australian Commission on Safety and Quality in Health Care: http:// www.safetyandquality.gov.au/ our-work/healthcare-associatedinfection/antimicrobial-stewardship/ resource-materials/ References available on request.
Rivaroxaban use in cancer patients: Misleading conclusion To the editor:
Response
While rivaroxaban has clear attraction for use in the cancer patient population, the ASCO guidelines clearly state that this is not recommended at present due to lack of evidence. I believe this should’ve been stated in the article. The subgroup analysis of the pooled results quoted a lower recurrent VTE that was not statistically significant (probably due to small sample size and likely post hoc analysis). Incidence of major bleeding was reduced may well be due to the fact that the drug was less effective in this group of patients. I have a handful of cancer patients developed DVT/PE while on Xarelto for AF. Until phase III evidence is available, the use of this drug in our patient population for treatment of VTE should be actively discouraged.
We thank Dr Tsoi for her comments regarding the recent article on rivaroxaban in the April 2015 edition of Circuit. We certainly agree with all the points she raised. As she mentioned, there is some attraction for the use of these newer agents in the cancer population and the intention of the article was to delve into that concept given its recent PBS listing but not to directly advocate for its use in cancer patients at this time. In the conclusion, we attempted to remind the reader while there is possibly a role, more research is needed and this medication could prove to be an option in the future. We would like to make it clear we were not recommending the use of rivaroxaban in cancer patients (until there is sufficiently robust evidence supporting any use) and apologise the article and conclusion may have come across that way.
Dr Daphne Tsoi MBBS MSc FRACP Medical Oncologist Fiona Stanley Hospital St John of God Hospitals — Subiaco & Murdoch Adjunct Associate Professor University of Notre Dame Australia
Chau-Anne Pham—Pharmacist, Icon Cancer Care Adelaide Author
Ben Stevenson—General Manager, Pharmacy Services, Icon Cancer Care Editor
What’s new The benefits and cost savings of oral capecitabine treatment in rectal cancer Miranda King, Icon Cancer Care Townsville Fluorouracil (5-FU) based treatment is currently regarded as the standard of care in the neo-adjuvant treatment of locally advanced rectal cancer.1 5-FU is an antimetabolite chemotherapy drug indicated in the adjuvant setting and advanced stages of colorectal cancer.2 Its effectiveness relies on its activation to cytotoxic metabolite forms that are distributed to body tissues with the highest concentration in gastrointestinal mucosa2. Typically patients with locally advanced rectal cancer will receive six weeks of continuous 5-FU (at 225mg/m2/day) with concurrent radiotherapy prior to surgery.3 Capecitabine is a pro-drug of 5-FU and its action involves three successive enzymatic steps.2 Unlike fluorouracil, it is readily absorbed in the gastrointestinal tract when taken orally.2 It has been established that oral capecitabine is non-inferior to 5-FU in relation to 5 year overall survival in patients receiving both neo-adjuvant and adjuvant chemoradiation for the treatment of locally advanced rectal cancer.1 Capecitabine is prescribed at a dose of 825mg/m2 twice daily on days one to five of each seven day cycle. This is taken concurrently with radiation for five to six weeks prior to surgery.4 Previously, capecitabine has only had a Pharmaceutical Benefits Scheme (PBS) listing for use in patients with breast cancer and advanced or metastatic colon cancer.5 However, as of March 2015, this medication is now available as a benefit on the PBS for use without restriction.5 In the past, a major barrier to accessing capecitabine in this patient group was its significant price due to not being PBS- listed.5 5-FU on the other hand is relatively inexpensive and PBS-funded, making it a far more financially viable treatment option for healthcare facilities.7 However, despite the low cost of 5-FU, when reviewing the overall treatment cost of using this medication inclusive of PICC line
insertion, cost of complications from intravenous treatment, consumables, as well as time spent in the day therapy unit, the final figures tend to favour capecitabine. In 2014, a retrospective analysis of the healthcare costs associated with the neo-adjuvant administration of 5-FU with radiotherapy to patients with rectal cancer versus oral capecitabine and radiotherapy was conducted. These costs were derived from the perspective of a public metropolitan hospital in Brisbane. Mean cost per patient and complication rates were recorded to provide a head-tohead comparison of the two modes of treatment. A total of 63 patients were identified, 33 patients for the 5-FU arm and 30 patients for the capecitabine arm. The mean healthcare cost over the six cycles of treatment with 5-FU included: Cost of insertion of a PICC line, cost of staff for procedure, cost of infusor device, drug cost, service fee and consumables. With all of these costs considered, the mean total cost was $999 for 5-FU patients and this was compared to $969 for capecitabine patients, which was cost of drug only (at the time of the analysis). Median total time spent at the hospital each week was also calculated for each patient group. 5-FU treated patients required a consultation and a visit to the day therapy unit for PICC line flushes, disconnection/reconnection of infusor device and dressing change. Their median total time per cycle was 123 minutes compared to 60 minutes for capecitabine patients who required only a consultation with the doctor. The incidence of diarrhoea, hand and foot syndrome (HFS) and rash occurred similarly in both treatment groups, however the presence of the PICC line resulted in several complications that were unique to the 5-FU patient group. Of all complications reported in the 5-FU arm, 70% of them were attributed to the PICC line. Refer to table 1.
In the capecitabine arm, a total of 30% of patients experienced reportable side-effects and only one patient did not complete treatment due to coronary artery vasospasm, a serious adverse effect which occurred in both treatment arms. An issue unique to treatment with capecitabine is compliance. Possible solutions to this are staged supply (week by week dispensing) and documentation by prescribers of the amount of tablets supplied. This is an opportunity for pharmacists and doctors to collaborate to ensure appropriate prescribing and education around dosing administration and side effects. As we continue to make advances in the treatment of cancer, the patient experience is a factor that should be considered when making decisions regarding therapeutics. The cost benefit of using an oral alternative in this patient group is only a small part of why oral therapy is an attractive option. The complication rate with 5-FU therapy also impacts on quality of life during an already stressful time. The removal of PBS restrictions on capecitabine offers prescribers more choice when treating this disease and may offer reduced side-effects and time saving benefits to our patients. References available on request. Table 1. Unique complications of 5-FU Complication type
No. of patients
Failed PICC insertion
1
PICC requiring re-insertion
3
Severe PICC dressing reaction
2
PICC dressing dislodgment
2
PICC insertion length adjustment
2
Blocked PICC line
3
Incomplete infusion after seven days
4
PICC exit site infection
2
Clot (requiring Clexane)
1
Systemic infection requiring IV antibiotics
1
PICC line damaged (break in line)
1
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New Drug Brief Ellipta® Inhalers Sally Attalla, Epic Pharmacy Port Macquarie Recent developments in maintenance therapy of Chronic Obstructive Pulmonary Disease (COPD) have delivered not only new drugs (bronchodilators with extended duration of action that enables once-daily dosing, and a more potent ester of the corticosteroid, fluticasone 1), but also new breath-activated devices to improve delivery of the drugs to the target tissues in the lungs. One such combination of new respiratory medications and delivery device is the Ellipta® range of dry powder inhalers (DPIs) from Glaxo SmithKline (GSK), summarised in Table 1. Favourable characteristics for a DPI include: i. Medium inspiratory airflow resistance through the device which yields optimal drug deposition in the lungs without being overly reliant on achievable inhalation airflow rates in COPD patients3,4 ii. Ease of use of the device, particularly in the COPD population whom often have other comorbidities affecting cognition & coordination3,5,6 Ellipta® devices are pre-loaded with medication, an advantage over devices that require the insertion of a capsule of medication and consequently more manipulation.
Figure 1 How to use the Ellipta® inhaler 7
Only open the cover once you are ready to take a dose. If you open and close the cover without inhaling the medicine, the dose will be lost.
“Click”
Click
Inhale
Close
Slide the cover down until you hear a ‘click’
Put the mouthpiece between your lips, and close your lips firmly around it
Remove the inhaler from your mouth and breathe out slowly and gently
Take one long, steady, deep breath in and hold this breath for at least 3–4 seconds
Slide the cover upwards as far as it will go to cover the mouthpiece
While holding the inhaler away from your mouth, breathe out as far as is comfortable
Table 1 Ellipta® Products 2 Device
Contains
Actions
Incruse Ellipta®
umeclidinium
Long-acting muscarinic antagonist (LAMA) bronchodilator
Anoro Ellipta®
umeclidinium, vilanterol
LAMA bronchodilator, Long-acting Beta2 agonist (LABA) bronchodilator
Breo ™ Ellipta®
fluticasone furoate, vilanterol
Corticosteroid (high potency), LABA bronchodilator
Furthermore, Ellipta® performed favourably in the two abovementioned characteristics in recent studies, airflow characteristics4 and ease of use5. Incorrect use of an inhaler by patients can lead to poor compliance and treatment failure.6 The healthcare
provider’s ability to demonstrate the correct operation of any inhaler and supervise the patient’s capacity to use it are therefore very important. Figure. 1 demonstrates the key features and correct technique for the Ellipta® device. References available on request.
If you have any queries regarding Circuit content and authors please contact the Epic Pharmacy Practice Unit by email: circuit.editor@epicpharmacy.com.au Every effort has been made to ensure this newsletter is free from error or omission.
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