**Transcript of Cyberseminar**

**Evidence-based Synthesis Program**

**Antimicrobial Stewardship Programs in Inpatient Settings: A Systematic Review**

**Presenters: Gregory Filice, MD, and Nancy Greer, PhD**

**December 16, 2013**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact Nancy.Greer@va.gov.*

**Moderator:**We are just at the top of the hour here. I would like to take a moment to introduce our presenters here. Dr. Nancy Greer is a Health Science Specialist within the Center for Chronic Disease Outcomes Research at the Minneapolis VA Medical Center. She is the program manager for the Minneapolis site of the VA Evidence-based Synthesis Program. 

Dr. Gregory Filice is a Professor of Medicine, Adjunct Professor of Epidemiology at Community Health in the School of Public Health and Chief of the VA Infectious Disease Section. Dr. Filice received his infectious disease training at Stanford University School of Medicine and the Palo Alto Medical Foundation. He studies antimicrobial therapy, specifically strategies to optimize prescribing to improve outcomes and prevent resistance. 

They will be joined today by Dr. Matthew Goetz. He is the Chief of Infectious Diseases, VA Greater Los Angeles Healthcare System, Program Director at the UCLA Affiliated Program in Infectious Diseases, and a UCLA Professor of Clinical Medicine. His research interests include strategic treatment and long-term complications of HIV infection and antimicrobial utilization and infection control. 

And with that, Dr. Greer, I would like to turn things over to you.

**Dr. Nancy Greer:**Okay, thank you. Well, the topic today is “Antimicrobial Stewardship Programs in Inpatient Settings,” and I would like to acknowledge our coauthors and collaborators as well as our external group, our technical expert panel and peer reviewers.

Just briefly disclosure information. This report is based on research conducted by the ESP Center here at the Minneapolis VA and was funded by the Department of Veterans Affairs, Veterans Health Administration Office of Research and Development, Quality Enhancement Initiative. No investigators have any affiliations or financial involvement that would conflict with the material presented.

Briefly, the VA ESP Program is sponsored by the VA Office of R&D. It was established to provide timely and accurate syntheses, reviews of healthcare topics identified by VA clinicians, managers, policy makers, as they work to improve the health and healthcare of veterans. There are four ESP sites.

The purpose of the review is to provide evidence syntheses on important clinical practice topics relevant to veterans and there is a broad nomination process, so, people who are listening, if there are topics of interest, you can go to the website listed here and nominate topics for these reviews.

The program has a steering committee that oversees the research, the operations. Each report has a technical expert panel involved as well as external peer reviewers and policy partners, the stakeholders interested in the particular report. And the final reports are disseminated on the VA HSR&D website and throughout the VA through management briefs and so on.

So back to the current report, this was a systematic review: Antimicrobial Stewardship Programs in Inpatient Settings. And now I will turn it over to Greg.

**Dr. Gregory Filice:**Good day to everybody. We were interested in this project because there is a huge amount of antimicrobials used in the United States, more than three million kilograms administered to human patients in the US in 2009. Antimicrobial use in humans influences the patient being treated and the surrounding ecosystem, and of course, we have to add that to the antimicrobials that are used in animals and other parts of the environment. 

We know from extensive experience that inappropriate or excessive antimicrobial use is associated with increasing antimicrobial resistance among microbes, higher incidence of antimicrobial-associated *Clostridium difficile* infection, other drug-related toxicities and increased healthcare costs. And very importantly for patients, inadequate antimicrobial use is associated with increased mortality and increased morbidity in people with infectious diseases.

Antimicrobial stewardship programs, the focus of our review, are efforts to optimize antimicrobial use, including selection of drugs, dosage, route or duration of antimicrobials. And the goals of programs are typically to improve patient outcomes, prevent or reduce antimicrobial resistance, reduce adverse antimicrobial effects and deliver cost-effective therapy.

Cost-effective is a carefully chosen term. Programs almost all do not try to get people to prescribe the cheapest antimicrobial. The goal is to have optimal antimicrobial therapy which will result in savings from a reduced morbidity and mortality.

Antimicrobial Stewardship Programs may include multidisciplinary teams including infectious disease physicians, clinical pharmacists, clinical microbiologists, infection control specialists and epidemiologists. They often have support and collaboration of hospital leadership and administration. They often make use of computer systems for decision-making and/or tracking of antimicrobial use, infections or adverse drug events.

Antimicrobial Stewardship Programs vary quite a bit, but commonly they include the following types of interventions: 

· Prospective audit with feedback

· Formulary restriction and preauthorization

· Education

· Guidelines and clinical pathways

· Antimicrobial cycling

· Order forms

· Streamlining or de-escalation of therapy

· Dose optimization

· Parenteral to oral conversion

This is my first call as a leader. So I think it is okay for people to stop me and ask me questions as I go along. At the end. Okay. Well, if there is something that I say that people do not understand, please save that question for the end.

Prospective audit with feedback is a sort of jargon that we in the business use. It means that there is a team that looks at antimicrobial use and gives feedback to docs. I am not sure we will ever get to a specific definition of that. And the other program maybe definition is antimicrobial cycling, which meals that some hospitals have tried changing the antibiotics that are used month-by-month typically to see if by changing the antimicrobials the microbes are sort of kept off-base and they do not develop resistance to one set of antimicrobials.

I think I will move on, but look forward to questions and comments at the end.

So the purpose of our review was to synthesize the evidence about the effectiveness and harms of antimicrobial stewardship programs implemented in adult inpatient settings. I am going to turn it over to Dr. Greer.

**Dr. Nancy Greer:**Okay. So we identified or developed the following key questions for this review, and this was with input from stakeholders and our technical expert panel. The first key question: What was the effectiveness of inpatient antimicrobial stewardship programs on the following: and our primary outcome was patient-centered outcomes such as mortality, readmission, *C. difficile* infection and length of stay. And secondary outcomes, antimicrobial prescribing, microbial outcomes and costs.

Our second key question: what are the key intervention components associated with effective inpatient antimicrobial stewardship?

The third key question: Does effectiveness vary by: hospital setting or suspected patient condition?

Fourth key question: What are the harms of inpatient antimicrobial stewardship programs?

And the last question: Within the included studies, what are the barriers to implementation, sustainability, and scalability of the programs?

So our methods—we identified a Cochrane review by Davey in 2005. That included a search of literature to 2003 and this review partially addressed our key questions. We conducted our own MEDLINE search from 2000 to June 2013 based on their strategy and limited to the English language. We also identified citations from existing systematic reviews, reference lists of retrieved articles and suggestions from our experts in our panel and the peer review.

While we were in the middle of our review, the Cochrane review was updated with a search to 2009, so our review included only studies that were not in this updated Cochrane review.

We excluded from our review studies done in nursing homes, pediatric populations, medical or surgical prophylaxis, viral or fungal infections, tuberculosis. We also excluded provider education or community like public health campaigns; and importantly, we also limited our review to studies that were randomized controlled trials, controlled clinical trials, controlled before and after studies, or interrupted time series. 

We used standard methods for data extraction, having one person extract and verification by a second person. We assessed risk for bias of the included studies using the Cochrane Effective Practice and Organization of Care method; and we assessed strength of evidence for the patient-centered outcomes.

We categorized studies by intervention type, as you will see. This was difficult for some studies because they involved multiple interventions or hybrid interventions. They did not fit nicely into those categories.

We were unable to pool the data, which is often common in systematic reviews, due to heterogeneity of the interventions and the study designs, patient populations and the way the outcomes were reported.

We triaged over 6,000 abstracts from our literature search. We did a full-text review of 559 articles and ultimately included 35 studies. And again, these were studies that were not in that existing Cochrane review. 

So just to look at some of the results from the Cochrane Review quickly: they included 89 studies published through 2009. Their focus was on prescribing outcomes rather than patient-centered outcomes, and they categorized interventions as either persuasive, which included education, audit and feedback; restrictive, order forms, restrictions on the formulary; and structural, electronic medical record, decision support systems.

For their patient-centered outcomes, since those were our primary outcomes, for mortality they found that interventions to increase guideline compliance for patients with community-acquired pneumonia reduced mortality. But it is important to note that that conclusion is based on four studies, four of the 89 that they included in the review.

Interventions to increase effective prescribing, which was reported in three studies, and interventions to decrease excessive prescribing, reported in 11 studies, were not significantly associated with mortality.

Other patient-centered outcomes: the interventions to decrease excessive prescribing had no effect on length of stay and that was reported in six studies. They were associated with increased hospital readmissions and that was reported in five studies; and they were associated with a reduction in *C.**difficile* infection and that was reported in four interrupted time series studies.

The prescribing outcomes, which was the focus of this review, included data from 76 of the 89 studies. They calculated a median effect size with all prescribing outcomes, so they just pooled everything together, whether it was a change in the use of a specific antimicrobial or duration of IV therapy—anything that was related to prescribing got pooled together. A positive sign indicated a change in the intended direction. They found that all types of interventions were associated with improved prescribing. A median change in prescribing ranged from 4% to 46% and this was across the intervention types, persuasive, restrictive, structural and by study design. 

They also broke it out by what were the findings and the RCTs versus the interrupted time series and so on.

So now to turn to our results, we included 35 trials. There were nine RCTs, four controlled clinical trials, two controlled before and after studies and 20 ITS studies. We categorized the studies by interventions, so we had 14 that we included that we considered primarily audit and feedback. Most of them were multi-component, but we tried to categorize them according to what seemed to be the primary emphasis. There were five formulary restriction and preauthorization, eight with guidelines, with computerized decision support and four that were sort of protocol or policy implementation.

This is our Clinical Outcomes table. This is kind of busy, but a few things. There is a lot of not-reported or one study cells, so these outcomes were not reported in the studies.

I should say that a positive sign indicates that there was a significant association favoring the antimicrobial stewardship. This double tilde or whatever indicates that there was no difference between intervention and control, and then the negative sign indicates that the intervention favored the control group.

So just to point out some of the highlights here, in Mortality, these are our outcomes, these are our categorizations. These are our outcomes. These are our categorizations of the interventions. 

There were nine studies of audit and feedback that found no association between the intervention and mortality. Three studies of formulary restriction and so on. So you see a lot of the double tilde symbols indicating that there was very little association  of these interventions with the clinical outcomes, which is a good thing in that they did not cause increased mortality at all.

All right. The next table here is prescribing outcomes and again the same orientation, a lot of these outcomes were not reported or one or two studies. Some of the important findings were that there was decreased use of antimicrobials, a positive association with the stewardship program in eight studies. A similar formulary research and preauthorization, a positive association showing a beneficial effect of the antimicrobial stewardship program and decreasing use of antimicrobials. One of the other use outcomes was compliant or appropriate use of antimicrobials, so they were in two of the four guidelines with feedback studies and two of the four guidelines without feedback studies—again, a positive association.

The other outcome is duration of treatment and there were five of the 14 audit feedback studies that reported this outcome all showing a positive association with decreased duration of use with the stewardship program and similarly with the protocol studies also an association.

The other primary secondary outcomes in Key Question 1 were microbial outcomes and here there were nine studies that reported microbial outcomes. Six reported improvement, meaning decreased infection or resistance. Three reported no difference. 

On the cost outcomes, that is not a correct number. There were 14 studies that reported drug costs. That was the most commonly reported cost outcome. And of the 14 studies, all reported decreased costs with the stewardship program. Four of them were significant; two of them were not significant; and eight did not report a significance; but the direction of improvement was to decrease costs in all cases.

Key Question 2 was asking about Key Implementation Components and there were no particular studies of this, so this was all author opinion that was offered in six studies. Some of the key implementation elements were consistent and persistent effort from qualified personnel, effective communication skills and support from electronic medical records systems or computerized decision support systems.

For Key Question 3, the Effectiveness in Different Settings or Different Suspected Conditions, the Davey review included nine studies from VA medical centers and the results were similar to the overall body of evidence. There was unchanged mortality in one study; decreased C. difficile infection in two studies; mixed results for prescribing and that was reported only in three studies; and decreased infection in three studies.

None of the studies that we identified that were not in the review were from VA studies. Most of the studies we found were from university-affiliated hospitals.

Nine of our studies were conducted exclusively or reported data for ICU settings and the results were similar to the overall results. Most studies included patients with “any suspected infection.” We did identify seven studies that were exclusively respiratory infection, and again the results were similar. So it is hard to identify differences based on ICU setting versus other respiratory infection versus other.

Harms of Programs: there really was not a whole lot reported. There were two studies that were basically anecdotal, sort of speculation, anecdotal evidence of inappropriate switch to a narrow-spectrum antimicrobial; and termination of a program that was speculated to be due to provider dissatisfaction with prescribing prescriptions. But it was not systematic assessment of that.

Our fifth question was about Barriers to Implementation, Sustainability and Scalability. Barriers were reported in four studies, two which included interview or survey data from participants. Some of the barriers: 

· Lack of familiarity and experience, awareness of the intervention, the guidelines and so on 

· Disagreement with the guidelines or the presence of conflicting guidelines from different societies

· Lack of communication between professionals

· And some of the organizational constraints on time and so on

Sustainability was only reported in one study and they did a five-year study. Over that five-year study the use and cost decreased. But then when the study was terminated, they noted the costs increased in the following year.

And scalability in terms of ability to rule out an intervention in multiple places, this was not reported. We did not find any studies that reported on scalability.

So I will turn the talk back over to Greg.

**Dr. Gregory Filice:**We found that antimicrobial stewardship strategies can decrease antimicrobial prescribing and limit costs without evidence of substantial harms.

The greatest body of recent evidence is from studies that were of audit and feedback programs as opposed to the other interventions I mentioned earlier.

Systematic review of earlier studies provided evidence of comparable effects for persuasive and restrictive interventions. I am referring now to the Davey study from 2005 and the update. 

The evidence base for our Key Question 1 was substantial; a lot of papers reporting on outcomes, drug outcomes, fewer on patient outcomes. But the evidence base was much, much smaller and less substantial for the Key Questions 2-5 that Nancy reviewed.

Most of the studies were not designed to adequately assess the impact on mortality or other clinical outcomes. There were really two reasons for that. Many of them were not really oriented to that; they were oriented more towards drug usage. The other main reason is that the power needed to assess clinical outcomes is often greater than the power needed to study prescribing outcomes, and so many of the studies would not have been adequately powered or were under inadequately powered to look at clinical outcomes. 

There were several suggestions for improving adherence to antimicrobial stewardship programs that arose from our review. They include the following:

· Involvement of stakeholders and opinion leaders in guideline and program development. In other words, if the ID docs want to develop a program, they should involve all sorts of other stakeholders in the clinical environment and opinion leaders in the design of the program and the recommendations so others buy-in.

· Studies were more effective if they had quality improvement cycles; that is, they had some way of formatively evaluating the program.

· Studies were better if the developers understood the prescribing culture. There is plenty of evidence that prescribing varies from setting to setting and that it is sort of a cultural phenomenon. 

· And studies are more likely to be effective if there is collaboration between physicians and pharmacists, again mostly based on opinion rather than evidence.

There were limitations to the studies and therefore the conclusions of our review:

· They include the fact that when each article was analyzed for the quality of evidence, most of them had low quality of evidence because of study design, size, et cetera. 

· There were relatively few randomized controlled trials.

· There was a limited ability to control for secular trends or other confounding variables in prescribing habits in hospitals.

· For studies on *C. difficile* infection, there was the distinct possibility of regression to the mean. What I mean by that is that most of the studies that include the specific focus on the incidence of *Clostridium difficile* infection were in settings with high rates of *C. difficile*, sometimes outbreaks. The incidence of *C. difficile*, like the incidence of many things that happen in hospitals or in the community, fluctuates with time; and if people study when the incidence is high, the incidence may have regressed to the mean and dropped just because of secular trends. So it was often difficult to know whether an intervention really impacted the incidence of *C. difficile* or whether it dropped just because of regression to the mean.

· Because of the heterogeneity of interventions and combinations of interventions, most of the studies that we did of specific interventions have not been replicated in multiple centers.

· In some of the studies, prescribing improvements were often not sustained or long-term followup was not reported.

· Most of the studies we looked at were done at academic medical centers. So generalizability to other settings like community hospitals or other types of healthcare organizations is difficult from the evidence available.

· Within academic medical centers, there are substantial variations in settings, structures, patient bases and culture. There is a strength to this in that our review indicates that stewardship has an impact, usually a positive impact, in diverse setting. But the weakness of this observation is that it is hard to ensure that each specific intervention works well across all settings.

· We found few studies that reported on the harms of stewardship intervention. Most were not designed to identify harms and most would not have been adequately powered to recognize them, regardless of the intent.

We spent a lot of time thinking about future research needs. Given the complexity of antimicrobial prescribing, conducting well-designed studies is a difficult task.

Large healthcare organizations should consider organizing stewardship activities that are likely ongoing within the organization to provide useful information on comparative effectiveness of different intervention types. In other words, large healthcare organizations have a large stake in whether antimicrobials are being used effectively, and we think it would be wise to devote resources to being sure that the kinds of activities we participate in and spend resources on are making a difference.

Despite the many shortcomings that I briefly mentioned, the overall evidence suggested that antimicrobial stewardship interventions are associated with improved, intended outcomes, most of those outcomes having to do with antimicrobial usage. The evidence suggests that these interventions are associated with short-term improvements over one to three years because most of these studies were relatively short-term. The evidence does not really support evaluations of longer-term time scales. So absence of evidence.

The literature supports hospital and healthcare system implementation of sensible, practical antimicrobial stewardship intervention to improve outcomes.

Throughout our study, we were thinking about recommendations we would provide to the larger audience. We were also always thinking about recommendations that would apply to VA settings since we are a VA organization participating in a VA-sponsored review.

We recommend that the data on antimicrobial use by clinical unit, type of patients, provider groups and individual providers should be gathered to determine where antimicrobial use might be less than ideal or is in need of improvement. So now we are thinking about recommendations to a health organization or a hospital that might want to see if they can improve antimicrobial use.

The first thing we would recommend is that people study about the usages at the current time and see where there might be room for improvement.

Existing infection control programs, microbiology laboratories, pharmacy services, infectious disease physicians, electronic medical record systems, continuous improvement programs, and staff or trainee education and certification programs are all things that hospitals are likely to be doing already and could contribute to an antimicrobial stewardship activity. But we recommend that hospitals utilize these many sources of expertise and other kinds of resources to contribute to stewardship activities.

Leadership should also be kept well informed of the stewardship activities and involved in planning; and leadership support for both development and ongoing support of stewardship activities is essential.

We strongly recommend that formative evaluation be done to identify effective stewardship programs. That is, whether the programs that are implemented are effective and whether the programs that have been implemented need modification.

This is the end of our comments and we would be very interested in any comments from you or questions. Both Dr. Greer and I will be happy to respond. And I think before the questions from the larger group, Dr. Goetz may want to comment.

**Dr. Matthew Goetz:**Thank you. Can you hear me?

**Moderator:**We can hear you, yes.

**Dr. Matthew Goetz:**Excellent. I had – okay. So, hi. I am pleased to have the opportunity to comment on this report, which was charged jointly by – it was charged primarily by Antimicrobial Stewardship Task Force, which is a combined effort of the VA National Infectious Disease Service and the Pharmacy Benefits Management group. I am speaking in my position as chair of the Implementation Subcommittee of the Antimicrobial Stewardship Task Force, so you see our new logo up there and who we are.

I thought it might be useful for the audience, who may be rather heterogeneous, to review the charge of the Stewardship Task Force, which was established approximately two and a half years ago now. Their charge is “To optimize care by developing, deploying and monitoring national levels to teaching plans for the improving of antimicrobial therapy.” The objectives are to summarize current performance and improvement prioritize priorities for stewardship, to catalog where possible ongoing measures for antibiotic improvement activities across the VA, to develop plans to leverage the VA’s robust clinical information tools and employing key leadership actions in response to specific needs. 

The group, as many of you will know, has moved beyond that and has proposed and distributed sample policies and projects for local facilities to work on. Our goal in working with the ESP to promote the evaluation of literature that they have performed and now reported on was to ensure that the recommendations that we put forth, the projects that we establish and the policies that we recommend are based as firmly as possible upon the available evidence. At the same time we be aware of where the gaps of evidence are to be able to be attuned to ongoing research and hopefully to be able to encourage further research to answer questions about what should be done, how it should be done and how it might be best implemented. This report, therefore, is quite useful in that regard.

I try to summarize in the next couple of slides what I regard as some of the key messages. Of course, the first important message is that we, while the data are not, as you know, at the highest possible quality, the data consistently show that stewardship activities are proved and intended outcomes primarily related to antimicrobial usage and that harms have not been observed in many substantial ways. And this clearly supports the business case for antimicrobial stewardship if we look at nothing other than the costs of antimicrobial therapy. Of course we are interested in far more than simply costs, such as clinical outcomes and microbial outcomes, e.g. resistance, but as noted in the report, these are much harder to come by.

We also hear clearly that we need data to drive programs. And what I think the report shows us is there are really two types of data we need. We need an ability to analyze data, to look at the performance of individual sites over time, and that ideally we should be utilizing the corporate data warehouse and other robust national resources to allow for cross-institutional comparisons, recognizing that cross-institutional comparisons are extraordinarily tricky because of all the nuances that go into the data. And unfortunately, consequences or conclusions can be drawn if we are not careful in that regard.

Very clearly as well the report, I think, shows that multiple discipline, routes of communication and education are needed. These are very clearly multi-disciplinary interventions. Consensus-building is a key part in success.

It is also apparent from elements of the report that the intuitive observation that leadership needs to be involved and informed. Their support is absolutely essential, as is local buy-in for a number of constituencies. It was explicitly said that the need to have infectious disease physicians and pharmacists work together is important. But I think it was implied in the report and perhaps stated in the body of the report itself that also the other stakeholders, ICU docs or hospitalists or ED docs, buy-in by these local champions is also crucial. 

And as a general rule, we of course do not know all the answers when implementation is started. The reference to formative evaluation I think is a very key message that the Stewardship Task Force needs to take away, as well as emphasized the site-to-site variations which clearly indicate that site level customization of programs is an essential component.

In terms of the what to do, clearly audit and feedback programs provide the greatest amount of evidence in favor of stewardship. I think we lack some information, though, as to how did you audit the feedback because this, again, I think can exist on a spectrum of persuasive versus restrictive intervention and the literature is very complicated, as was mentioned. Overlap and how terms are used such as audit, has audited and feedback, overlap with antibiotic time out, streamlining and de-escalation I think are things that we need to think about. 

And I would say finally that we need to recognize that while the ESP Review does not answer all questions and more research is needed, the evidence is more than sufficient to promote prudent prescribing practices; hence the logo of the Antimicrobial Stewardship Task Force. 

I just want to touch back the research. Of note that there are many stewardship attempts and it is very interested not only in this evidence review but a number of research projects, some of which are being conducted, I know by Dr. Filice, some of them in Minneapolis and other sites and other people. I know some in Sylvain DeLisle in the VA work at the Baltimore VA looking at outpatient prescribing, projects that I am aware of looking at asymptomatic bacteriuria and how we can better manage that led by Cal Gupta in Boston and Barbara Trautner in Houston. Projects I am participating with are with the Salt Lake City VA group and Peter Gladstone is here through one of the CREATE projects looking at how to best implement stewardship. 

So the Stewardship Task Force is very interested not only in what has gone on in reviewing the previous evidence, but also in looking at new evidence which is being developed. This report goes a long to help us move forward.

Those are my comments.

**Moderator:**Great. Thank you so much, Dr. Goetz. We actually do not have any pending questions at this time. For the audience, we have got plenty of time for questions. This is a great opportunity to get your questions submitted. We will read those out over the phone for a response from any of our presenters from today’s session. We will give you guys a couple minutes to get those typed in and we can start going through those.

Do any of our presenters – do you guys have anything you would like to add at this time while we are waiting for questions?

Okay, still ...

**Dr. Matthew Goetz:**I just want to say that from the perspective of the Stewardship Task Force, I just want to again emphasize the importance of having this really fine-grained understanding of the available evidence that supports our activities and again give credit to the fact that it helps really establish a research series of questions. There were references to a comparative section of research made in a proposal. Speaking personally, I think that the VA is really an ideal environment in which to answer many questions about the scalability of stewardship programs, given the large size of our healthcare system; the generalizability of the effectiveness of interventions given the heterogeneity of our VA facilities. And just really look at long-term outcomes given the robust informatics systems that we have in the VA. So I am hopeful that we can all look forward to many advances in this field coming from VA investigators.

**Dr. Gregory Filice:**Dr. Goetz, this is Greg Filice. I would second that. I think the other thing about VA centers that differs from others is that we are more of a single-focused organization without having to look at funding sources and insurance and without having a lot of outside providers but more likely having people who are at least partially employed by VA or fully employed by VA. I think we have a clear mission, a more focused mission. And I think the VA is a tremendous environment to do the kind of studies that are needed. We were frankly a little surprised to find studies from VAs in the earlier body of evidence, but none among the 35 studies we reviewed. Maybe they are all in press as we speak.

**Dr. Matthew Goetz:**Right. I think there is a lot of work. I thought you had the Rattinger study from ...Oh, that is an outpatient study, excuse me. I misspoke there.

**Dr. Gregory Filice:**No, that is true, and we are following up with an outpatient review. We have been hard at work on that and so we hope to have that available soon for the audience and anybody else who is interested.

**Dr. Matthew Goetz:**Good.

**Moderator:**Great, thank you. We have gotten a couple of questions in here for Dr. Goetz: Who involves more is it that is working on outpatient stewardship?

**Dr. Matthew Goetz:**Sylvain Delisle who is a pulmonary critical care physician that has had ongoing studies looking at outpatient use of antibiotics for pneumonia and respiratory tract infections. I think he recently concluded some studies which were just published in POOS 1 and has ongoing projects with the CDC, which may be being performed outside the VA at this time.

**Moderator:**Great. Thank you. And the next question that we have here: You mentioned IT support?

**Dr. Matthew Goetz:**Yes.

**Moderator:**Anyone working on decision support for prescribing antibiotics?

**Dr. Matthew Goetz:**I think there are a number of different groups that have developed a varying decision support. And quite frankly, we have Greg Filice online here, who gave the review. I know that they have developed a robust system in Minneapolis VA which I believe you are in progress of implementing elsewhere in the VA.

**Dr. Gregory Filice:**That is true. We have a decision support for both inpatient and outpatient use and it exists in most of the VISN 23 hospitals and it is likely it will be implemented in another hospital outside of VISN 23 in the near future. They are in the process of putting it into their CPRS system.

And then we have published a paper showing that use of the Decision Support System at the Minneapolis VA is associated with improved prescribing. That was an observational study sort of quasi-experimental. It did not fit within the four categories for this review, but was published about a year ago.

**Dr. Matthew Goetz:**All right. And then in addition, Sylvain Delisle’s system for a stewardship program for outpatient antibiotics at Decision Support Modality and we just concluded in Los Angeles a 12-month pilot project looking at a Decision Support System for antibiotic time-out or reconsiderations of antibiotic therapy three days into treatment, which we are quite encouraged about. And we are looking at funding mechanisms to allow us to implement that in other VAs in the future to look at the scalability and generalizability of that intervention, which a few sites in VISN 21 are taking up on their own right now.

There are a number of different kinds of projects which are of the small to moderate scale but show promise.

**Moderator:**Great. Thank you. And that is actually all the questions that we have received in at this point. I am not sure if anyone else is still taking any questions in or if any of the three of you have any final remarks you would like to make. It looks like we may be closing out early today.

**Dr. Gregory Filice:**Well, I would like to just pick up on the Decision Support question, which is a good one. The number of studies that examine the effect of Decision Support in our review and earlier reviews was relatively small, but the conclusions of those were positive; I would say uniformly positive. And I think there is promise that Decision Support could be quite helpful. Honestly it is probably going to be more helpful or the likelihood it would be helpful is probably greater if decision support is a part of a multi-dimensional stewardship program. But it is just a very useful tool that pharmacists and physicians can point to.

This is somewhat anecdotal, but at our hospital, the Decision Support System has really impacted the antibiotic prescribing culture. Even for people who do not use the Decision Support System, they are aware of what our system recommends and they try to use it whenever they can. So I think, and for reasons that have already been mentioned, a lot of them center around Vista and CPRS, the VA is in very good position to have Decision support.

**Dr. Matthew Goetz:**I want to echo all of those stories. I strongly and agree with the promise of Decision Support as we move forward.

**Dr. Gregory Filice:**I think one of the overall impressions that we got when we did the review is that, as I mentioned, the evidence from the articles, the quality of the evidence, was weak. But that reflects the way stewardship studies tend to be done. It is difficult with current funding patterns from VA and other places to get hundreds of thousands or millions of dollars to do a very satisfying, scientifically satisfying, randomized controlled trial. But when you read these articles, you have the impression of front-line clinicians, front-line pharmacists recognizing there is a problem, looking at the resources that they have available to them and then putting together a study with existing resources. The designs varied. The quality of evidence varied. But as you step back and sort of looked at the overall body of evidence, it is positive. It is consistently positive.

Now there is a possibility of publication bias. But the overall impression that these studies, done in a number of different ways by a number of different sort of organizations or collections of people of various flavors of antimicrobial stewardship consistently show the same thing, that you can affect antimicrobial prescribing over the short run. And so I would second what Dr. Goetz said, which is that there is plenty of evidence for VA hospitals or other hospitals to at least look at what they are doing and try to find sensible approaches that are supported by multiple stakeholders and that reflect the views of multiple stakeholders, to try to improve what we do.

**Moderator:**Okay, great, thank you. We have not received any other questions in. It looks like we are going to wrap up a little bit early today. For all of our presenters, I really want to thank you for your time to putting this together and presenting for today’s session. We really appreciate all of the time that you all put into this.

For the audience, if you all can hold on just another minute, I am about to put up a feedback form and we would love to hear your feedback on the session. We really do implement a lot of the suggestions that you guys do put forward to us, so if you could fill that out, we really would appreciate that. 

And thank you, everyone, for joining us for today’s HSR&D CyberSeminar and we hope to see you at a future session. Thank you.

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