2020 Edition 3
clinical initiatives, research and current updates in treatment
Special Edition World Antimicrobial Awareness Week is from 18 - 24 November 2020. It aims to raise awareness of antimicrobial resistance and promote the responsible use of antimicrobials.
How long is a “course” of antibiotics? Glenn Valoppi, Antimicrobial Stewardship Pharmacist – Slade Pharmacy, Epworth Hospital Richmond Antibiotics are commonly prescribed for the treatment and prevention of infectious diseases. The most appropriate drug, dose, route of administration and duration of therapy should be used to achieve the best outcome for the patient while minimising the risk of harm. These potential harms include adverse effects (e.g. nausea, hepatitis), development of superinfections (yeasts, C.difficile), and colonisation with resistant organisms (e.g. ESBL E.coli, vancomycin-resistant E.faecium (VRE)).
For how long are antibiotics actually needed? Recommendations for the duration of therapy of antibiotics might be based on patient outcomes, for example continuing an antiviral drug such as ganciclovir until viral loads in the blood are under control. Other recommendations are often based on research comparing different lengths of therapy before stopping treatment or changing from injectable to oral options. These studies often compare a new (shorter) treatment plan with current standard care. If there is no worse outcome for patients using a shorter course, this may lead to a change in treatment guidelines. The likelihood of treatment success is the same, but the risk of harm from the antibiotic is
reduced. There are additional potential benefits in terms of reduced treatment costs, reduced lengths of stay, and reduced IV-line related complications related to intravenous treatment. Research is emerging indicating that clinical outcomes are similar between short and long courses of antibiotics for many common infections. To determine what the most appropriate duration might be, it is important to know what the diagnosis is for your patient.
How much longer does my patient need treatment with antibiotics? The efficacy of antibiotics is related to how much of the drug gets to the site of infection rather than the actual administration method. Every day of treatment with an active drug should be counted when reviewing the patient, regardless of the route. Consider a patient with severe pyelonephritis caused by E.coli who is now stable and ready for discharge on oral antibiotics. They received 2 days of IV piperacillin-tazobactam started in the Emergency Department; followed by 3 days of IV ceftriaxone in hospital once the microbiology findings were reported. Treatment was then de-escalated to oral amoxicillin for the last 2 days. Guidelines suggest a total treatment duration of 10 to 14 days for severe pyelonephritis. The
discharge prescription should specify for how long to continue oral antibiotics; for a further 3 to 7 days only.
Completing the course Once a diagnosis is clear, and the patient is improving, a treatment duration (in days) can be tailored to the patient. Continuing therapy until this point might be considered ‘Completing the Course’. Continuing antibiotics until a standard packet is emptied may not achieve this. A standard pack size cannot be the right fit for all patients; who may be taking different numbers of pills per day (e.g. clindamycin), have different recommended treatment durations (e.g. cystitis vs. osteomyelitis), or who have already received part of the treatment (initial IV therapy, or imprest supply). Some commercial pack sizes, or PBS quantities, are not necessarily a good fit for recommended therapy. Patients may require more than one pack of amoxicillin or clindamycin capsules to achieve the right dose for the right duration. A standard pack of seven tablets of trimethoprim is more than required for cystitis in most women, an appropriate number for cystitis in most men, and too few for treatment of prostatitis.
Where else to look for information? Useful summaries have been recently Continued on page 2
published by Australian resources including:
What to do (especially on discharge):
¬
Therapeutic Guidelines: Antibiotic Prescribing in Primary Care
Think about total duration of therapy required for your patient. ¬
¬
National Centre for Antimicrobial Stewardship (NCAS): It’s about time: Antibiotic Duration
Remember the number of doses in a standard packet may not match the needs of your patient.
¬
Don’t forget how many days of treatment have been previously administered in hospital (IV and oral).
¬
Think twice about the advice to ‘Finish the Course’; advise the patient exactly how long the course of treatment is, as recommended for the particular indication in guidelines, and how to appropriately dispose of any leftover antibiotics.
¬
Australian Prescriber (NPS): Optimal antimicrobial duration for common bacterial infections - Also as a Podcast
A neat summary produced by the John Hunter Hospital, NSW:
The duration of antibiotic therapy required to adequately treat your patient may be much shorter than you think!
References are available on request.
Having the guts for Antimicrobial Stewardship - the effects of antimicrobials on the gut microbiome Rachel Taylor, Director of Pharmacy, Epic Pharmacy Port Macquarie We humans all have a complex microbial ecosystem in our gastrointestinal tracts. We depend on microbial activities to assist digestion, provide vitamins, resist pathogens and assist with the immune system and metabolism. The adult gut contains more than 1kg of bacteria; there are thousands of different types of microorganisms in the gut and these can be further divided into different ‘taxa’ or families of microorganisms. Elements of contemporary living, such as urbanisation, highly processed diets, improvements in hygiene and
use of antibiotics can all have a profound impact on the composition of gut microbiota, and the potential consequences of such an impact are largely, at this point, unknown. ‘Hygiene hypothesis’ links increasing rates of autoimmune disorders such as asthma and inflammatory bowel disease in people living in developed countries to changes in the intestinal microbiota, with organisms being vital in promoting normal immune development. The area of gut microbiota research is
fascinating and expanding rapidly. This Antimicrobial Awareness Week edition of Circuit highlights research regarding the effect of even ONE dose of antimicrobial on the gut microbiota. One study investigated three subjects over ten months. In a six month period, the subjects received two 5-day courses of oral ciprofloxacin. The distal gut microbiota were examined pre- and post-antibiotic administration and the organisms that made up the microbiome assessed for variability and diversity.
Some day to day differences were observed, but largely remained stable, until there was deliberate disturbance by giving antibiotics. The effect of ciprofloxacin on the gut microbiota was “profound and rapid with a loss of diversity and a shift in community composition�. By one week after completion of the antibiotic course, they noted that the microbiome started to return to its usual state, and at the end of the study it had stabilised, but remained altered from its initial state. A marked loss of diversity in the microbiota of mice for at least 28 days has been demonstrated following a single dose of clindamycin, with a prolonged loss of specific taxa. This
insult to the microbiota also resulted in a sustained susceptibility to Clostridioides difficile induced colitis. The authors suggest that these data are consistent with human studies, and that the successful treatment of C.difficile infection in humans with faecal microbiota transplantation (stool transfer from a healthy donor) is evidence that microbial populations are critical for resisting colonization and infection by this type of pathogen. Another study has shown a direct correlation between the diversity of gut microbiota and mortality following allogeneic haematopoietic stem cell transplantation. Those patients with a less diverse microbiome showed
an overall three year survival of 36%, compared to 67% for those with a high diversity of gut microbiota (see Figure 1). The groups were compared as to type of conditioning regime, transplant source, use of Total Parenteral Nutrition and antibiotics given. In examination of associations, beta lactam antibiotics and metronidazole were associated with decreased diversity whereas fluoroquinolones were not; the authors suggested that this is due to the different activity against anaerobic organisms. Intravenous vancomycin was also significantly associated with decreased diversity.
Figure 1: Plot of diversity and overall survival and transplant related mortality.
Derived from: Taur et al. (2014) Blood 124(7):1171-82
It is clear that there are risks to the diversity of the microbiome associated with antibiotic therapy, and that this may have substantial subsequent impacts. Whilst there are currently no direct cures or preventative measures for these effects, research is ongoing in therapies such as faecal transplants, as well as potential synthetic alternatives. One study identified that the administration of a particular combination of four microorganisms interacted to directly inhibit the growth
of vancomycin-resistant Enterococcus (VRE) in the intestines of mice, giving promise to future alternatives to faecal transplants. (VRE is a serious treatment-resistant pathogen that can dominate the gut after antibioticinduced microbiota destruction.) In addition to these promising therapies, it has been shown that DNA sequencing of the microbiota could identify patients at high risk of developing sepsis, and potentially enable targeted administration of microbes to prevent mucosal domination and subsequent invasive infection.
During Antimicrobial Awareness Week where we spend a bit more time thinking about wise use of antimicrobials, there are some important things we could perhaps consider: is there a need for an antimicrobial in this patient? Which antimicrobial is best? And can the duration of therapy be carefully considered to lessen the disturbance of the gut microbiota by use of antimicrobials? References are available on request.
For breaking news, follow us on social media facebook.com/epicpharmacy Twitter: @epic_pharmacy Instagram: @epic_pharmacy
Surgical Antibiotic Prophylaxis: Ironing Out the Bugs Bettina Kirk, Pharmacy Practice Unit Advisor – Antimicrobial Stewardship What is appropriate surgical antibiotic prophylaxis (SAP)? Surgical antibiotic prophylaxis (SAP) refers to the use of antibiotics for the prevention of surgical site infections (SSIs), and it is the most common indication for antimicrobial use in Australian hospitals. While SAP has been conclusively shown to reduce the rate of SSIs when it is appropriately used, this benefit should always be weighed against the potential harms associated with antimicrobial use (e.g. side effects, development of antimicrobial resistance).
For the majority of procedures, a single preoperative dose of SAP is sufficient to prevent SSIs. Extending the duration of prophylaxis postoperatively (IV or oral) has not been shown to further reduce infection rates, but can cause patient harm (e.g. subsequent infections with resistant pathogens, acute kidney injury, C. difficile infection). There are a small number of exceptions to this; refer to guidelines. In all cases, any postoperative SAP should not continue beyond 24 hours.
SAP is not required for all procedures The requirement for SAP depends on the procedure; many operations do not require an antibiotic. Generally speaking, SAP is indicated if there is a higher risk of postoperative infection (e.g. colorectal surgery), or where the consequences of a postoperative infection could be serious, even if the risk is low (e.g. an infected prosthetic implant or cardiac valve). To minimise the potential for harm, whilst maximising benefits of using antibiotics in surgery, evidence-based guidelines should be followed, including these key principles: ¬ SAP should only be used when there is a clear indication, as per guideline recommendations (either local hospital guidelines or Australian Therapeutic Guidelines (eTGs)) ¬ The choice of antibiotic should reflect the organism(s) most likely to cause infection. For most procedures, cefazolin is recommended and provides adequate coverage against skin flora. Any relevant patient factors such as existing infection, drug allergy or increased risk of infection with drug-resistant bacteria must also be taken into account. ¬ The intravenous route is recommended in most scenarios; antibiotics applied topically or by irrigation are not supported by evidence, and should not be used. ¬ Timing is crucial. SAP must be administered before “knife to skin” to achieve effective drug concentrations in the plasma and tissues at the time of incision. For cefazolin, the dose should be administered no more than 60 minutes prior to surgery commencing.
Update on SAP in Australia The Surgical National Antimicrobial Prescribing Survey (sNAPS) is a standardised auditing tool used by many Australian hospitals. It provides a comprehensive overview of the prevalence and appropriateness of antimicrobial prescribing in surgery. The latest summary report (2018) including data from 5637 surgical procedures described: ¬ Where pre/intraoperative SAP was administered (4030 procedures), 38% of prescriptions were inappropriate o 12% of these procedures did not require any antimicrobial o Where antimicrobials were required, the most common reasons deeming the prescriptions as inappropriate were incorrect timing (51%), incorrect dosage (23%) and the antibiotic spectrum being too broad (12%) ¬ Of the procedures where no antibiotics were given, this was inappropriate in 9.1% of cases, as SAP was indicated. ¬ 34% of patients undergoing surgery received at least one antimicrobial postoperatively; this was inappropriate in 62% of episodes, with the most common reasons being incorrect duration and incorrect dose or frequency ¬ The median days of duration of SAP ranged from 2 – 9 days across a variety of surgical specialties The report highlighted priority areas for improvement initiatives, including the
importance of the key principles outlined above and following the antibiotic selection, dose, timing and duration recommendations in evidence-based guidelines. Since 2018, it has been a mandatory requirement for Australian facilities to monitor the appropriateness of SAP prescribing, and provide evidence of action taken to address any issues identified in order to meet the National Safety and Quality Health Service Standards for hospital accreditation.
Support and resources available To support facilities address identified issues or gaps, assist with strategies for improvement and provide evidence required for hospital accreditation, our pharmacies have produced an updated resource toolkit for SAP, including: ¬ A study report summarising the results from a recent multi-site project across Icon Group investigating AMS activities and recommendations aimed at reducing prolonged SAP duration ¬ Resources for use in hospitals and pharmacies, including: o A Surgical Antibiotic Prophylaxis Guideline template, for local consultation and adaptation, updated to align with the latest eTGs o 1-page specialty-specific SAP guideline posters for orthopaedic, plastic, abdominal and urological surgery o “Duration of Surgical Antibiotic Prophylaxis” poster o Education presentations ¬ Tips and guidance for implementing SAP guidelines locally For more information or copies of these resources and study report, please contact PharmacyPractice@icon.team or your local pharmacy department. Resources are 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.
epicpharmacy.com.au