Beneficial Outcomes of Antimicrobial Stewardship

Antimicrobial stewardship (ASP) is an area of practice that is both an art and a science. ASP is ever changing and dependent on up to date application of evidence and knowledge translation strategies that are effective and measurable. The objectives of ASP are to reduce inappropriate antimicrobial use, optimize therapies, focus on improving patient outcomes and support sustainable antimicrobial susceptibility for the future. These broad objectives will be discussed herein and resources will be provided throughout to help the reader apply different strategies to their practices in order to integrate or improve ASP programs.

Reducing inappropriate antimicrobial use

One of the cornerstones of stewardship is to combat misuse and overuse of antimicrobials by providing education and applying evidence-based use of antimicrobials. Many studies have found that 20 to 50 % of all antibiotics prescribed in hospital settings are either considered unnecessary or inappropriate.¹ Antimicrobial therapy and prophylaxis in hospitals has been reported to be inappropriate in up to 60% of cases according to a study that synthesized data from multiple references.² Some of the reasons referenced for inappropriate antimicrobial use included:²

• Uncertainty of diagnosis,
• Comorbidities that were complex in nature,
• Lack of specialized training or experience,
• Lack of knowledge regarding local resistance patterns, and,
• Inappropriate interpretation of antimicrobial results.

All of these factors may lead to increased risk of adverse outcomes such as increased morbidity, mortality, healthcare costs and emergence of resistant pathogens.

Determining appropriateness of antimicrobial prescribing
A study assessing appropriateness of antimicrobial prescribing of hospitalized patients found that 44% of patients received an antimicrobial at the time of audit and of these, 30% were considered inappropriate and approximately 40% of empiric therapy was inappropriate.² More than half of prescribed antimicrobial therapies were for community acquired infections with 45% being started within the first 3 days of hospitalization.² This type of information stresses the need for a focus on ASP strategies at the outset of antimicrobial regimen initiation to determine indication, duration and other factors related to monitoring.

5 Strategies to optimize antimicrobial use
Some of the strategies that can be considered to reduce inappropriate use of antimicrobials:

• Review all empirically prescribed antimicrobials for an indication,
• Review antimicrobials used for prophylaxis to determine necessity and appropriateness,
• Consider optimization of antimicrobials on a regular basis (ie. route and duration)
• Ensure that guidelines and clinical or local resources are easily accessible,
• Consider creating local antibiograms and providing education on interpretation.

Improving patient outcomes

There are many benefits to ASP, particularly when a multidisciplinary approach is taken and when monitoring and a pharmaceutical care plan are established. Below are some of the interventions that can help improve patient outcomes through antimicrobial optimization.

Beta-lactam allergy review
An important component of selection of optimal antimicrobial therapy is gathering an accurate allergy history for patients presenting with a beta-lactam allergy on their profile that require surgical prophylaxis or treatment of an infection. Up to 15% of those who are hospitalized report a penicillin allergy and close to 95% will tolerate penicillins without any notable adverse outcome.³ Having a label of a penicillin allergy on a patient’s profile can result in use of second-line therapy for prophylaxis or treatment of infection;³ therefore safely delabeling can result in improvement of patient-centered outcomes. An example of where beta-lactam allergy delabeling can result in improved treatment of infection can be seen in treatment of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia where giving an alternative treatment, such as vancomycin, can result in higher incidence of treatment failure than when beta-lactams are used.³3 BC Women’s and Children’s Hospital carried out a penicillin allergy delabeling project and an interview by Firstline on this topic can be found here.

Optimizing antimicrobial duration
Optimizing the duration of therapy can reduce length of antimicrobial use, length of stay and risk of antimicrobial-resistant infections. A recent example focusing on optimizing duration of long-course antimicrobial therapy comes from a pilot randomized controlled trial comparing duration of therapy of 3 to 6 weeks of antimicrobials for treatment of diabetic foot osteomyelitis after surgical debridement.⁴ The authors found that a shorter course of antimicrobials in the population studied provided similar incidence of remission and adverse events related to antimicrobials as a 6-week course.⁴ Studies such as these that investigate duration of therapy, route of antimicrobial administration and other factors that can optimize antimicrobial use will help to improve patient outcomes, reduce adverse events and improve overall antimicrobial use and resistance when applied in the appropriate populations.

De-escalating antimicrobial therapy
Antimicrobial de-escalation and streamlining strategies involve changing broad-spectrum antimicrobial therapy to targeted therapy based on culture, susceptibility and diagnosis.⁵ De-escalation can also involve changing an IV antimicrobial to oral route or discontinuing antimicrobials based on culture results and diagnostic considerations.⁵ A study found that when recommendations were made for for streamlining of therapy they were applied in more than 80% of cases of which more than 97% completed therapy with the streamlined antimicrobial.⁶ Furthermore, the project noted an annualized savings of over $100, 000.⁶ A more recent study published in 2017 assessed the impact of antimicrobial de-escalation in treatment of pneumonia for those within a Veterans Healthcare Administration in the USA.⁷ Authors found that de-escalation was associated with decreased length of stay with a mean difference of 0.28 days, not associated with increased 30-day readmission and did not affect Clostridiodes difficile rates.⁷ There are many studies that have shown the patient and health-care related benefits of appropriate de-escalation of antimicrobials, therefore this ASP strategy can often be applied in either policy form such as automatic stop-dates, IV to PO step down or consultation based discussions to optimize antimicrobial therapies.

Reducing adverse outcomes

ASP initiatives have resulted in reduction of secondary infections such as Clostridiodes difficile, and therapeutic drug monitoring can reduce risk of neurotoxicity and nephrotoxicity. The section below will share strategies and to reduce adverse outcomes and improve patient safety through ASP initiatives.

Clostridiodes difficile (C. difficile) infection (CDI)
According to the Centre for Disease Control and Prevention (CDC), people are 7 to 10 times as likely to develop C. difficile while taking antibiotics and during the month after cessation of antimicrobials. Use of antimicrobials has been associated with increased risk of CDI with results from studies conducted as early as 1980s showing the importance of infection prevention and control (IPAC) measures in CDI.⁸[^’]⁹ Limiting antimicrobial use and broad-spectrum antimicrobial therapy is a major and modifiable risk factor for development of C. difficile.¹⁰ The CDC has created a comprehensive guide to provide interventions and recommendations for prevention of CDI in acute care facilities with IPAC recommendations and suggestions to engage in ASP programs with a reference to the Core Elements of a Hospital Antibiotic Stewardship Program. Another great resource is a 2019 review article that provides an overview of risk factors associated with CDI, reviews pathogenesis and provides guidance regarding treatment.¹¹ The IDSA and SHEA released an updated guideline for management of CDI in Adults June 24, 2021 which may or may not be applicable to regions in which you are practicing.¹² It is important to note that treatment of CDI and recommendations may vary by country and be guided by available resources and antimicrobials.

Improving patient safety through therapeutic drug monitoring
A review article relating ASP to patient safety initiatives astutely points out the importance of therapeutic drug monitoring (TDM) programs for clinical and economic outcomes.¹³ TDM is often performed for vancomycin and aminoglycoside drug level monitoring to ensure efficacy and safety of antimicrobial use. A resource created by Public Health Ontario that focuses on different ASP strategies discusses therapeutic drug monitoring and measurement as well as interpretation of serum drug concentrations in order to maximize efficacy and minimize toxicity of antimicrobials.¹⁴ Examples of TDM resources from across Canada are shared as reference and to provide ideas for the user to create their own program. There are many resources such as these that can be accessed through different organizations that are leaders on antimicrobial stewardship research and larger centers that focus on teaching strategies for antimicrobial use optimization.

Maintaining antimicrobial susceptibility

Antimicrobial resistance is recognized as a global health crisis according to the World Health Organization and was recently discussed in detail in a United Nations Interagency Coordination Group (IACG) Report on Antimicrobial Resistance. Sustainability of antimicrobial susceptibility requires optimizing resource utilization across an entire continuum of care that addresses and encourages appropriate and sustainable use of antimicrobials on a local, national and global scale.

Strategies to address antimicrobial sustainability on a global scale
Strategies that are intended to address increasing rates of antimicrobial resistance require a system-wide perspective in pharmaceuticals, food and agriculture, natural resources, and information systems.¹⁵ Some of the strategies on national or international level that can focus on sustainability of antimicrobial susceptibility include:¹⁵

Evaluating and assessing accessibility to antimicrobials, Ensuring availability of quality products, Involving experts to improve and change patterns of use, Utilize therapeutics and dosing strategies that are evidence based, Improve diagnostics and access to resources, Address affordability on a global scale, and, Ensure that antimicrobial sustainability is a government-level priority.

Strategies to address antimicrobial sustainability at an institution level
There are also strategies that can be applied at a local or institutional level that focus on sustainability of antimicrobial use. Often these strategies involve continual education as well as audit and feedback. A study conducted at a large academic centre in the USA assessed the impact of formulary restriction with prior authorization on antimicrobial use.¹⁶ Authors note that prior authorization of doripenem use was successful at ensuring appropriateness of antimicrobial selection.¹⁶ Another study assessed the impact of a program that was started in British Columbia, Canada in 2005 named “Do Bugs Need Drugs” with the aim of reducing the number of unnecessary antimicrobial prescriptions through education to the public and healthcare professionals on appropriate use of antibiotics.¹⁷ The project resulted in improved physician antibiotic prescribing and consumption of different antimicrobial classes commonly prescribed for upper respiratory tract infections.¹⁶ These are just two of the numerous examples of ASP strategies implemented on a local level that have shown impact on resource use, appropriateness of prescribing and other outcomes of interest related to antimicrobials.

Conclusion

Creating ASP programs, strategies and initiatives at a local, institutional and global level help to improve antimicrobial use, focus on patient-centered outcomes, reduce adverse effects associated with antimicrobials and can help to combat antimicrobial resistance.

5 Useful Resources

• Core Elements of Hospital Antibiotic Stewardship Programs / Antibiotic Use
  
• Antimicrobial stewardship-qualitative and quantitative outcomes: the role of measurement
  
• Vital Signs: Improving Antibiotic Use Among Hospitalized Patients
  
• Antimicrobial Stewardship: Importance for Patient and Public Health
  
• Identifying best practices across three countries: hospital antimicrobial stewardship in the United Kingdom, France, and the United States
  

Biography:
Dr. Mira Maximos (PharmD) is an inpatient and antimicrobial stewardship pharmacist specializing in infectious diseases, with @firstline as the Knowledge Mobilization pharmacist and is a research associate with the Centre of Excellence for Women’s Health. You can follow her on Twitter @miramaximos.

Conflicts of Interest:
Mira Maximos is employed with Firstline Mobile Health as a Knowledge Mobilization pharmacist.

Disclaimer:
This blog post is for information/educational purposes only, and does not substitute professional medical advice. Also please note that opinions are those of the authors and do not necessarily reflect that of their employers.

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