All Together Now Part 1: Cohesive Antimicrobial Stewardship

April 9, 2019

In 2013, experts in the fields of infectious disease, pharmacy and infection prevention came together to form a super-committee now known as DASON: The Duke Antimicrobial Stewardship Outreach Network. Their first task was to critically evaluate antimicrobial stewardship and determine which parts are feasible and meaningful. Interestingly, the committee found that the impact of stewardship on antimicrobial resistance had yet to be well-documented. If ensuring that antibiotic resistance isn’t increasing or spreading is one major goal of stewardship, then why aren’t we measuring this? More broadly, how can we ensure that the goals and language of stewardship are aligned and met?

How did “antibiotic stewardship,” a term with 1016 entries in Pubmed in 2018, enter the clinical clinical microbiology or infection control vocabulary? The first article to use the term in relation to antibiotic use was written by two American scientists and published in 1996 . In 1997 the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) began using the term in their guidelines for keeping hospitals free of drug-resistant organisms. The term slowly became popular in the literature until 2011, when the numbers of PubMed citations containing antimicrobial stewardship soared.

Pubmed citations on antimicrobial or antibiotic stewardship over the past 20 years.

Once guidelines for best practices were available, many hospitals all over the world began building stewardship teams. High quality, meaningful research began to emerge that demonstrated the positive effects of interventions that limited inappropriate antibiotic use. In 2015 the CDC released a national action plan to reduce antibiotic resistance. This plan was supported by $160 million in new investments provided by Congress to continue to meet national goals. These included slowing the emergence of resistant bacteria, developing new therapeutics and improving international collaboration and capacities for antibiotic resistance prevention.

When you look through the outcomes the CDC hopes to achieve from this initiative, the first item on the list is to improve antimicrobial stewardship in hospitals. This is a wonderful goal, a goal that seems reasonable and attainable. So what’s the challenge here? Well, antimicrobial stewardship seems to mean different things to different people. Everything from the size of the stewardship team to the way interventions are delivered varies greatly among institutions. We have made progress, but as far as antimicrobial stewardship practice goes, our practices are about as scattered as the stars in the sky.
An example of the variety of stewardship interventions that have been performed since 2008.

What We Have Learned and What We Could Improve 

Years of good research has shown that when we change antibiotic use to avoid unnecessary antibiotics, to select the appropriate antibiotics, and to dose them correctly, we see improved patient outcomes. We know that putting less unnecessary selective pressure on microorganisms reduces or slows the development of antibiotic resistance. Many organizations around the globe have implemented stewardship practices and demonstrated other benefits, including reduced costs, length of stay in the hospital and improper antimicrobial use. These are all meaningful steps in the battle against drug resistance. The larger problem we face now is lack of consistency or cohesion. They say that "teamwork makes the dream work" and solving the drug resistance issue will push our teamwork abilities to the limit. Here are some areas that could use fine-tuning:

The Challenge of Exploring Changes in Antibiotic Resistance

The actual definition of drug resistance is well understood and used practically everywhere. If an organism is not killed by an acceptable level of antibiotic in the laboratory then it is considered to be resistant. However, if we are going to tackle the enormous task of tracking resistance over time, we need attempt to standardize the way we think about resistance in various settings and at the very least make sure it is well-defined in the literature.
 
Many researchers have applied a stewardship intervention and then analyzed the percentage of susceptible isolates both immediately before and after the intervention. While this does suggest whether an intervention was successful or not, these studies rarely discuss the number of samples that were collected for microbiological testing during these time periods. Without knowing this value we are left with only the isolates that received susceptibility testing. Why does this matter? Knowing the number of specimens collected during these time periods would provide an understanding of increases in volumes, changes in testing procedures or differences between wards within a facility. It is important to note that not everything that grows in culture in the microbiology laboratory receives susceptibility testing, and knowing test volumes helps interpret what the burden of resistant organisms really is.
 
The implementation of a stewardship program is likely to encourage providers to perform less unnecessary testing. In doing this, the samples that are sent to the lab might be from patients with a more severe illness or a history of chronic illness and infections and these samples might be more likely to grow organisms that have increased resistance to antibiotics, raising the percentage of reported resistance in the facility overall. Diagnostic and antibiotic stewardship influence may also change the way specimens are collected (reducing the dilution of specimens or not performing in line suction, for example) and the influence of this on resistance patterns is unclear. Understanding testing volumes and processes in the evaluation of stewardship programs is essential to fully understanding the context antimicrobial resistance rates are presented in.
 
Some studies attempt to describe the change in resistance over time but fail to discuss the types of specimens tested or the hospital units they were collected from, while others clearly define the specimen types that were tested as well as whether the patient was in the ICU or not. Knowing the location of a patient with a resistant organism can be important, as behaviors and training of staff differ greatly between wards within the hospital. Additional complications arise because laboratories are using different versions of susceptibility testing protocols and interpretations of results (CLSI, FDA and EUCAST), as well as different instrumentation and commercial methods for susceptibility testing. It is impossible to ask every laboratory to do things in the same way, so it is imperative that the methods used are well-defined in the literature.
Example of results showing changes in resistance for organisms tested before and during the implementation of an AST program. This program included pharmaceutical and infection prevention interventions. The number of total specimens collected during these periods is not noted, so it is unclear if changes in reported resistance is due to changes in testing or specimen collection.

Lastly, while some studies define resistance as lack of susceptibility to a drug based on an MIC determined in the laboratory, others define it based on the presence resistance genes (determined by molecular testing). The relationship between traditional methods of testing MICs and molecular methods are rarely discussed together when evaluating clinical outcomes and effectiveness of stewardship programs.

Antibiotic Stewardship Programs Need a Common Language 

It is imperative that we start standardizing terms used in stewardship to begin building a vocabulary in common within the field. While the effect of stewardship on decreasing costs and antibiotic usage has been well documented, the effect of stewardship on resistance over time has not been. This question seems impossible to answer because provider behavior varies so greatly between hospital units and organisms and resistance patterns differ between specimen types. Without cohesion in the literature, it’s difficult to get a grasp on how to measure resistance over time when everyone is interpreting it differently. The first step is to ensure that all elements of resistance are well-defined and that incidence of antibiotic resistant organisms for different settings (inpatient, outpatient, transplant) is described.
 
Factors that should be considered when evaluating this metric include:
  • how specimens are collected
  • when patients are cultured
  • how extensively cultures are worked up (and organisms are fully identified)
  • how infection is defined as nosocomial .
 
Future work on standardizing these factors in research studies will be essential in understanding how rates of resistance are changing in each facility and across the world.

 What’s Next for Antibiotic Stewardship? 

There is an incredible amount of work to be done. While a strong foundation has been set, we need to continue to develop innovative ways to unify the world of antimicrobial stewardship. While the development of new therapeutics is essential, it will mean nothing if we have not changed our behavior. I leave you with some wise words by Helen Keller which readily apply to antibiotic stewardship efforts:
 
"Alone we can do so little; together we can do so much."

Author: Andrea Prinzi

Andrea Prinzi
Andrea Prinzi SM(ASCP),MPH,CPH has been a clinical microbiologist in Denver, Colorado for the last 11 years. She is actively pursuing her PhD in Clinical Science at the University of Colorado Denver.