1. Antimicrobial Stewardship David Meyer, PharmD Clinical Pharmacy Manager Fairmont General Hospital
Welcome to this presentation from Pharmacy Systems where we’ll discuss Antimicrobial Stewardship Program: The Basics

2. Objectives Identify types of antimicrobial resistance
Discuss multi-drug resistant organisms and possible treatment options
Describe the basic framework of an antimicrobial stewardship program
The primary objectives of this presentation are to
Identify the different types and causes of antimicrobial resistance
Discuss multi-drug resistant organisms and possible treatment options
And last we’re going to discuss the basic framework for establishing an antimicrobial stewardship program

3. Antimicrobial Resistance
Now before we get into discussing Antimicrobial Stewardship Programs, we first need to discuss how resistance to antibiotics develops, what resistant strains are out there, and some strategies to treat them
Antimicrobial resistance is recognized as one of the greatest threats to human health worldwide [1]. Almost 2 million Americans, each year, develop hospital-acquired infections resulting in nearly 100,000 deaths [3], the majority of which are due to antimicrobial resistance. Sepsis and pneumonia alone killed around 50,000 Americans and cost the system more than 8 billion dollars in 2006 [4]. The total cost of antibiotic-resistant infections is between 21 and 34 billion dollars each year.
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. 3

4. Antimicrobial Resistance: Selective Pressure
Selective antibiotic pressure results in polyclonal strains whereas inadequate infection control results in clonal strains commonly seen in colonization
Selective pressure results from environmental conditions that allow resistant strains of an organism to survive and then proliferate. In selective antibiotic pressure, the antibiotic kills or inhibits susceptible strains while the resistant strains remain, therefore the antibiotic contributes to the emergence of the resistant polyclonal strains.
Clonal strains, on the other hand, typically result from a lapse in infection control measures that allow for the transmission of the same (or clonal) strain from place to place.
Mulvey M R , Simor A E CMAJ 2009;180:

5. Antimicrobial Resistance: Mechanisms of genetic resistance to antimicrobial agents
Whether antibiotic resistance is intrinsic or acquired, the genetic determinants of resistance encode specific biochemical resistance mechanisms that may include enzymatic inactivation of the drug, alterations to the structure of the antibiotic target site, and changes that prevent access of an adequate concentration of the antimicrobial agent to the active site
Now we've discussed selective pressure as well as some of the different modes of resistance that exist. If we combine both of these concepts, we can start to understand how resistant organisms develop over time and why new mechanisms of resistance continue to emerge.
Coates A et al. Nature Reviews Drug Discovery 1, (November 2002)

6. Antimicrobial Resistance: Mutation & Selection/Acquired Resistance
Enzyme Inactivation
-lactamase production
ESBL production
Carbapenemase
New Delhi Metallo- -lactamase
Examples:
E. coli producing -lactamase or ESBL
Klebsiella producing carbapenemase
Now let’s review some of the different mechanisms out there.
Some organisms may acquire genes that enzymatically inactivate antimicrobials through selective pressure and mutation. This is most commonly seen with the evolution of resistant organisms bearing beta-lactamases. These novel beta-lactamase enzymes metabolize the beta-lactam rings of antimicrobial agents such as penicillin, rendering them ineffective in treating these mutated bacteria.
Examples include Extended spectrum beta-lactamases and Kleb-siella producing carba-pene-mase 6

7. Antimicrobial Resistance: Mutation & Selection/Acquired Resistance
Alteration of the target site
Altered protein binding
Altered DNA enzymes
Examples:
MRSA – methicillin-resistant Staph. aureus
PBP (Penicillin binding protein)-resistant Strep. pneumo
Ciprofloxacin resistance in Mycobacterium
Another mechanism of resistance involves alteration of the target site observed through changes in DNA enzymes or protein binding.
Anti-microbials often require specific conformations to bind to their target site appropriately.
Think of it as a lock and key model. If the organism changes the lock, the key (or anti-microbial we’re using) isn’t going to work. Some examples of this include MRSA, Penicillin-binding protein resistant strep pneumo, and mycobacterium resistance to ciprofloxacin 7

8. Antimicrobial Resistance: Mutation & Selection/Acquired Resistance
Decreased access to the target site
Efflux pumps - Antimicrobial is pumped out of the bacteria before it accumulates
Altered structure of outer membrane proteins or porins
Example:
Tetracycline TetK efflux in Staph. aureus
Imipenem-resistant Pseudomonas
Resistant organisms may also decrease access of anti-microbials to the target site through efflux pumps or by altering the outer membrane’s structural proteins.
Examples include tetracycline-resistant staph and imipenem-resistant Pseudo-monas 8

9. Examples of Common Resistant Bugs
Here’s a nice reference table that summarizes the different resistance mechanisms we just discussed. It’s important to note that this table is by no means a comprehensive list of all the possible forms of resistance but just a quick list of some of the most commonly seen mechanisms.
CMAJ February 17, 2009 vol. 180 no 9

10. Multi-Drug Resistant Organisms (MDROs)
Prevalent in hospitals & long-term care facilities
Not as likely to cause disease in LTCF (colonization)
Cause the same infections as non-MDROs BUT
Fewer antibiotic choices
Isolation
Increased length of stay
Increased risk of ADE
Increased mortality
= Increased $$$
Multi-drug resistance organisms are defined as organisms that are resistance to more than one class of anti-biotics.
They’re most commonly seen in hospitals and long-term care facilities, however, they typically present as an infectious disease in the inpatient setting and colonization in long-term care settings but this is not necessarily always the case
Organisms can be spread between patients in health care facilities, often through contaminated hands of health care personnel, contaminated equipment, or inanimate surfaces in hospital environment. This type of transmission is generally clonal in nature involving a single strain of the resistant organism.
It’s never good news that a patient is colonizing a highly resistant bug but it’s not absolutely necessary to treat these patients unless they’re showing signs and symptoms of infection.
These bugs don’t necessarily cause any new types of infections in patients but they are generally more difficult to treat, more expensive to treat, and especially present an increased risk to the patient. 10

11. MDRO Treatment Options: Community-acquired MRSA (Ca-MRSA)
Transmission
Contaminated hands
Skin-to-skin contact
Crowded conditions
Poor hygiene
Increased risk
Athletes, military recruits, children, Pacific Islanders, indigenous populations, men who have sex with men, animal owners, ED patients, cystic fibrosis patients, urban underserved communities, and prisoners
Community-acquired MRSA or methi-cillin resistant Staph Aureus is an increasingly common resistant organism whose transmission can largely be prevented by practicing good hygiene. A number of individuals are at an increased risk for acquiring this resistant bug and a short list of those individuals has been provided for reference here.
Clinical Microbiology Reviews, July 2010, p , Vol. 23, No. 3 11

12. Fortunately, the IDSA or Infectious Diseases Society of America has recently published new guidelines for Community-acquired MRSA infections January of The guidelines are available free of charge on their website idsociety.org
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: /cid/cir153

13. Mild-moderate infection
MDRO Treatment Options: Community-acquired MRSA (Ca-MRSA)
**Use varies greatly by site of infection, refer to IDSA MRSA Guidelines 2011**
Mild-moderate infection
Doxycycline or Minocycline
Caution with susceptibility tests
Clindamycin
Trimethoprim/Sulfamethoxazole
Severe infection
Vancomycin - PREFERRED
Daptomycin (NOT for pneumonia)
Linezolid (pneumonia)
Dalfopristin/Quinupristin
Limited by ADE arthralgias
Tigecycline (cSSTI, intra-ab)
Low serum concentrations
Telavancin (cSSTI)
Ceftaroline (cSSTI)
For mild or moderate community-acquired MRSA infections either doxycycline or minocycline may be effective but susceptibility tests must be performed on the individual agent to be used as this organism may show resistance to one agent and not the other.
Even then, in-vitro susceptibility tests may demonstrate efficacy but may not translate to actual in-vivo success so caution must be exercised when considering these agents. For mild or moderate infections, either clindamycin or trimetho-prim sulfa-methox-azole may be considered.
Severe MRSA infections may be treated with a variety of agents including vancomycin, daptomycin (except in cases of pneumonia), lin-ezolid, and dalfo-pristin quinu-pristin, as well as newer agents on the market including tige-cycline, tela-vancin, and ceftaroline. It’s important to adhere to the specific types of infections in which to use these agents whether it is a skin and soft tissue infection or pneumonia.
Agents that can be used as adjuncts include rifampin, gentimicin, and other beta-lactams
*Adjuncts: rifampin (also in combo with FQs), gentamicin, beta-lactams
Clinical Microbiology Reviews, July 2010, p , Vol. 23, No. 3
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: /cid/cir153
Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

14. MDRO Treatment Options: Penicillin-Resistant Strep. Pneumoniae (PRSP)
Causes respiratory tract infections and meningitis
Resistant to:
Penicillin G
*due to alteration in penicillin-binding proteins (PBPs)
Variable resistance to cephalosporins, macrolides, tetracyclines, clindamycin
Alternatives:
Amoxicillin/clavulanate
Ceftriaxone, cefotaxime
Respiratory quinolones
Linezolid
Vancomycin +/- Rifampin
Another multi-drug resistant organism is Penicillin-resistant Strep pneumoni-e which is often the cause of respiratory tract infections and meningitis.
This organism is resistant to Pen G due to an alteration in penicillin-binding proteins and demonstrates variable resistance to a number of antimicrobial classes including cephalosporins, macrolides, tetracyclines, and clindamycin
Alternative treatments include amoxicillin-clavu-lanate, 3rd generation cephalosporins, respiratory fluoroquinolones, the ketolide telithro-mycin, linezolid, and vanco with or without rifampin as an adjunct.
Am J Respir Crit Care Med ; 2005 ; 171 : Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

15. MDRO Treatment Options: Vancomycin-resistant Enterococci (VRE)
Usually Enterococcus faecium
Resistant to:
Vancomycin, Aminoglycosides, Penicillins, Quinolones
Treatment options:
Linezolid
Quinupristin/dalfopristin
Faecium only
Combination therapy recommended
Tigecycline
Daptomycin
Site Specific– Urinary Tract Infections
Nitrofurantoin
Fosfomycin
The last multi-drug resistant organisms we'll discuss is VRE or vancomycin-resistant enterococci which usually presents as Entero- coccus faecium. These organisms are resistant to vancomycin and typically some amino-glycosides and penicillins. When encountering these organisms, an ID consult is strongly recommended.
Alternative treatment options often depend on whether the infectious organism is E.faecalis or E. faecium as well as the site of infection. Notice the number of new agents that have emerged as effective agents in treating VRE infections.
CMI 16:555,2010 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
Clin Infect Dis. (2010) 51 (1): 15

16. MDRO Treatment Options: Pseudomonas aeruginosa
Resistant to:
Meropenem, Imipenem
Alternatives:
Possible evidence for extended-infusion carbapenems
Fluoroquinolones – cipro > levo
Anti-pseudomonal aminoglycosides (APAG)
Anti-pseudomonal penicillins +/- APAG
Ceftazidime, Cefepime +/- APAG
Aztreonam
Combos of Doripenem + Polymyxin B +/- Rifampin
Fosfomycin + APAG
Polymyxin B
Colistin
In the next series of slides, we’re going to discuss the primary multi-drug resistance organisms seen in clinical practice. In this overview, we’ll discuss the primary classes of antimicrobial agents these organisms are becoming resistant to and possible alternative antimicrobial agents that may be efficacious in treating such resistant organisms.
It’s important to stress that these lists of alternative agents have been shown to demonstrate efficacy at other institutions around the world but may not be efficacious in your individual institution. It’s highly recommended that you refer to your institutions local antibiogram for the most accurate and up to date resistance patterns in your place of practice.
The purpose of these slides is to demonstrate the variety of possible treatment strategies in cases of very resistant pathogens.
There is an emergence of carbapenem-resistant Pseudomonas largely driven by the selective pressure of fluoroquinolone’s for carbapenem-resistant strains deficient metallo-beta-lactamase. In these cases, there may be evidence for carbapenems administered through extended infusion as well as the variety of treatment options listed here.
Lister PD, Wolter DJ Clin Infect Dis 2005;40:S Livermore DM. Clin Infect Dis 2002;34:634-40
Am J Respir Crit Care Med ; 2005 ; 171 : Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
Antimicrob Agents Chemother October; 52(10): 3795–3800

17. MDRO Treatment Options: Extended Spectrum Beta Lactamase (ESBL)-Producing Organisms
Risk Factors for ESBLs in non-hospitalized patients
Recent antibiotic use
Residence in long-term care facility
Recent hospitalization
Age >65 years
Male
34% of ESBL-producing isolates from patients with no recent health care contact
Other resistant organisms include ESBL-producing organisms or Extended-spectrum beta-lacatamase producing organisms which, as their name implies, demonstrate resistant to broader spectrum beta lactam antimicrobials which we will discuss further in the next slide.
Risk factors for acquiring ESBL organisms include
Recent antibiotic use, typically within the previous 90 days
Living in a long-term care facility
Recent hospitalization
Older age
And Male gender
It’s important to note that a number of these organisms are contracted outside of the hospital setting
Ben-Ami R et al. Clin Infect Dis 2009;49:682-90

18. MDRO Treatment Options: ESBL-producing Organisms
Most commonly Klebsiella or E.coli
Resistant to:
2nd/3rd generation Cephalosporins
Aztreonam
Aminoglycosides
Fluoroquinolones
Alternatives:
Carbapenems (some emerging resistance)
Ertapenem for E. coli
In-vitro: Cefepime, Piperacillin/tazobactam, Tigecycline
Colistin
Fosfomycin
As you could see from the previous figure, Klebsiella pnuemoni-e represents the majority of ESBL organisms. These organisms are largely resistant to amino-penicillins, 2nd and 3rd generation cephalosporins, aztreonam, amino-glycosides, and fluoro-quinolones. Much of this resistance is driven by the use of cephalosporins and fluoroquinolones.
Alternative treatments include carbapenems, cefepime, piperacillin/tazobactam, tigecycline, and colistin. ESBL-producing organisms have largely remained susceptible to carbapenems but resistance has been shown to be on the rise in select strains.
Cefepime, piperacillin-tazobactam, and tigecylcine all demonstrate in- vitro activity but there is evidence they may prove ineffective in animals and humans. Some infectious strains are resistant to all of these except colistin but it's highly recommended to reserve this agent for only those highly-resistant strains such that it may remain just as effective in the years to come.
Am J Respir Crit Care Med ; 2005 ; 171 : Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed. 18

19. MDRO Treatment Options: Carbapenemase and New Delhi Metallo
KPC = CRE
Most commonly Klebsiella or E.coli
NDM-1 found in water samples in India
Resistant to:
All Carbapenems
Aminoglycosides
Fluoroquinolones
Alternatives:
Tigecycline
Colistin
As you could see from the previous figure, Klebsiella pnuemoni-e represents the majority of ESBL organisms. These organisms are largely resistant to amino-penicillins, 2nd and 3rd generation cephalosporins, aztreonam, amino-glycosides, and fluoro-quinolones. Much of this resistance is driven by the use of cephalosporins and fluoroquinolones.
Alternative treatments include carbapenems, cefepime, piperacillin/tazobactam, tigecycline, and colistin. ESBL-producing organisms have largely remained susceptible to carbapenems but resistance has been shown to be on the rise in select strains.
Cefepime, piperacillin-tazobactam, and tigecylcine all demonstrate in- vitro activity but there is evidence they may prove ineffective in animals and humans. Some infectious strains are resistant to all of these except colistin but it's highly recommended to reserve this agent for only those highly-resistant strains such that it may remain just as effective in the years to come. 19

20. MDRO Treatment Options: Acinetobacter
Up and coming “superbug”
Found in soil and water
Can live on skin & surfaces for days
Predominately a colonizing organism
Acineto-bacter often presents as Acineto-bacter baumannii and is often feared as a sort of superbug to many health care professionals. It’s found in soil and water, can live on the skin and other surfaces for many days, but it’s largely a colonizing organism that typically doesn’t beget infection.
So it’s important when Acineto-bacter is identified in positive cultures that the distinction between colonization and infection be made through the confirmation of the presence of infection and the accurate identification of the source of infection
Most patients colonizing Acineto-bacter originate from nursing homes or other long-term care facilities but there is a growing population of veterans carrying the organism back from the battlegrounds of Iraq and Afghanistan so it’s important to obtain an accurate history of the patients’ where-abouts before admission into the hospital setting. 20

21. MDRO Treatment Options: Acinetobacter
Therapy:
ID Consult!
Agents:
Carbapenems (building resistance as of 2005)
Susceptibility 32% to >90%
Ampicillin/sulbactam +/- Meropenem
Tigecycline - in combination only (e.g. + Amikacin)
Polymyxin B + Imipenem/cilastatin + Rifampin
Colistin
Susceptibility 55% to >80%
Other treatment therapies and combinations but Acinetobacter infections very MDRO: Mortality 20-50%
In cases of multi-drug resistant Acineto-bacter, an ID consult is highly recommended. Agents that have demonstrated success include Ampicillin-sulbactam in which the sulbactam component represents the efficacious entity, tigecycline which is recommended in combination ONLY (with amikacin for example which has proven effective in in-vitro studies), a combination of polymyxin b, imipenem/cilastatin, and rifampin, and colistin typically as a last resort.
Landman D et al. Arch Intern Med 2002;162: Kopterides P et al. Int J Antimicrob Agents 2007;30:409-14
Clin Infect Dis. (2010) 51 (1): Am J Respir Crit Care Med ; 2005 ; 171 :
Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed. 21

22. Antimicrobial Stewardship

23. What is an Antimicrobial Stewardship Program (ASP)
IDSA Definition
Antimicrobial Stewardship is an activity
that promotes:
– The appropriate selection of antimicrobials.
– The appropriate dosing of antimicrobials.
– The appropriate route and duration of
antimicrobial therapy.
Dellit TH, Owens RC, McGowan JE Jr et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for 1. developing an institutional program to enhance antimicrobial stewardship.
Clin Infect Dis. 2007; 44:159-77

24. Antimicrobial Stewardship – Why?
Not much in the pipeline
This is the disturbing reality of it. Every time the thought comes to mind that antibiotic resistance is something rare and intangible this type of data should haunt you. We’ve got a lot of great antimicrobial agents on the market right now from a variety of classes, including many new promising novel agents, but the fact is resistance develops on some scale to EVERY antibiotic. It’s just a matter of outpacing our bacterial competition.
Boucher et al. Clin Inf Dis 2009

25. World Health Organization (WHO) 10 x ’20 Initiative
Published in early 2010 by IDSA
WHO identified antimicrobial resistance as a major issue
That’s why the World Health Organization and IDSA came out with the 10x20 initiative. In 2010, IDSA launched the “10 × ’20 initiative” calling for the development of 10 novel, safe and effective, systemic antibiotics by These bad bugs need drugs. And fast.
Drug-resistant infections and related morbidity and mortality are on the rise in the United States and around the world. The World Health Organization has identified antimicrobial resistance as 1 of the 3 greatest threats to human health. This is no minor issue.
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: /cid/cir153
Clin Infect Dis 2010;50:

26. Antimicrobial Stewardship Programs (ASP)
Plethora of literature on resistance and ASP
Refer to local Antibiograms for most accurate resistant patterns
leadstewardship.org and ASHP Educational Webinars under Infectious Diseases subsection
Existing Webinars
Summarize IDSA Guidelines (2007)
ASP-supportive literature
Success stories
Personal & in literature
Our focus: Key points, focused approach, resources
Now that we've identified the problem, let's discuss what we can do to combat the problem by introducing Antimicrobial Stewardship Programs.
Antimicrobial stewardship programs (or ASPs) may sound like a new term for many of you but they've actually been around in some form or another in a number of larger teaching hospitals for the last decade or two. The Infectious Diseases Society of America has really brought this program to the forefront when they came out with their 2007 Guidelines on forming such a program. In this paper, the organization lays out the basic framework for forming an ASP and also provides some feedback for some common barriers that have evolved in response to the program over time.

27. Purpose Optimize clinical outcomes
Minimize unintended consequences of antimicrobial use
Toxicity
Selection of pathogenic organisms (e.g. C. diff)
Emergence of resistance
What is the purpose of ASPs?
The Purpose, as outlined in the guidelines is to:
Optimize clinical outcomes while minimizing unintended consequences including toxicity, selection of the pathogenic organism such as C.diff, and emergence of resistance
While improving patient care
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

28. ASP Guidelines Core Strategies
Prospective audit with intervention and feedback
Looking at antibiotic orders as they come, adjusting per pre-set guidelines
Formulary restriction with pre-authorization
UKMC: negative impact (let first dose go thru, intervene after)
Supplemental Strategies
Education, Education, Education
Guidelines and clinical pathways
Antimicrobial order forms (CPOE systems)
Combination therapy
De-escalation
Dose optimization
IV to PO conversion
Antimicrobial cycling (least evidence, most controversial)
There are certain strategies involved in establishing an ASP. Core Strategies include Prospective audit with intervention and feedback and Formulary restriction with pre-authorization. These strategies involve prospective adjustment of antimicrobial therapy based on pre-set guidelines while getting the antibiotic to the patient as quickly as possible. It is important to discuss with stakeholders the implications of pre-authorization at your institution.
Of the supplemental strategies, education is the most important. It’s important for those involved in ASP to familiarize themselves with the latest recommendations and studies out there while educating their co-workers and staff about what they’ve learned.
Other supplemental strategies involve
Guidelines and Clinical Pathways
Antimicrobial Order Forms often through Computerized Physician Order Entry systems
Combination therapy of Antibiotics
De-escalation once the infectious organism has been identified
Dose optimization
IV to PO conversion (as the saying goes – if the gut works, use it)
And last Antimicrobial Cycling which, of note, has the least evidence and is the most controversial since it often seems to just transfer resistance from the previously-used class of antibiotics to the class of antibiotics that replaced it
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:
ASHP Midyear 2010 CE Presentation – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution

29. CDC: Methods to Improve Antimicrobial Use
Passive prescriber education
Standardized order forms
Formulary restrictions
Pre-authorization
Pharmacy substitution
Multidisciplinary DUE
Performance feedback
CPOE
CDC:
The CDC has developed similar guidelines that follow the same train of thought; these include:
Passive prescriber education
Standardized order forms
Formulary restrictions
Pre-authorization
Pharmacy substitution
Multi-disciplinary drug utilization evaluation
Performance feedback
And last, Computerized Physician Order Entry

30. Guiding Tenets of ABX Use
1. Severe infection – start broad
Get it wrong = in trouble
2. Get it IN the patient quickly (actual administration)
First dose = most important
3. De-escalation of therapy is a necessity
Right drug = narrowest-spectrum with successful response, causing the least collateral damage
4. Treat only as long as appropriate
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
Despite trying to implement an ASP, there are certain guiding tenets that should trump everything else you do
ASP is a tricky balance. On one hand, there’s the importance of appropriate empiric therapy which is typically broad-spectrum so you know you’ve got the bug covered. On the other hand, it’s the broad-spectrum coverage that generally fuels the emergence of resistant strains. The key is quickly identifying the bug you’re dealing with and de-escalating antibiotic therapy as appropriate

31. ASP Team Members
Multidisciplinary problem that cannot be solved by one person
Core members (eventual compensation is ideal)
ID MD
ID Pharmacist
Adjunct members
Microbiologist
IT/Data Specialist
Infection Control Professional and/or Epidemiologist
ASPs MUST be conducted using a multi-disciplinary approach and cannot be operated uni-laterally. This is a very important point.
Who makes up the ASP team?
The Core Members are an ID physician and an ID pharmacist, both of whom should be compensated according to the IDSA
Adjunct members or members that should ideally be part of the team if possible at your institution include:
A microbiologist
An IT or data specialist
And an infection control professional and/or epidemiologist
Of course most ASPs initially don’t have the resources or personnel to complete the whole team but the Core Members are essential to the startup of the program. If the adjunct members aren’t able to be part of the team, it is critical to get their support for the program in order to increase likelihood of success.
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

32. Roles of the Team Members
Physician Champion
Knowledgeable in Infectious Diseases
Willing to teach untrained Pharmacist
Willing to help promote cause
Willing to work together
Respected by peers
Able to form working relationship with hospital administrator and pharmacy director
*sometimes the largest hurdle to overcome
Let’s explore the role of each team member.
As mentioned, the ID physician is a core member of an ASP an ideally should be trained in infectious diseases. If you’re not able to successfully recruit the lone ID physician at your institution, don’t let that discourage you. Although this team member is an essential part of a working ASP, what you’re really looking for is what’s called a physician champion.
A physician champion is READ SLIDE
Finding this member is sometimes the largest hurdle to overcome
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

33. Roles of the Team Members
Clinical Pharmacist
ID-trained or strong willingness to learn backed by a solid foundation in antibiotics
Helps establish program structure and protocol
Aids in creating and/or overseeing Antibiograms
Performs daily interventions
Continually educates medical and pharmacy staff
Raises pharmacy awareness and rallies support
Another core member – an ID pharmacist also presents another dilemma. Many institutions simply do not have a pharmacist formally trained in infectious diseases. In this scenario, the same goes for the pharmacist as the physician champion. What you’re looking for is a clinical pharmacist who has some infectious disease training at some level or another OR is willing to learn these skills from the physician champion as well as on his or her own.
The ASP pharmacist READ SLIDE starting with Helps
The pharmacist is often referred to as the “Worker Bee” performing odds and ends on the side, keeping the program viable until a complete team is able to be established
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

34. Roles of the Team Members
Microbiologist
Provides surveillance data for Antibiogram
Develops combination antibiotic Antibiograms
Reviews current diagnostic tests and investigates pros and cons of incorporating new, novel tests
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

35. Roles of the Team Members
Infection Control and/or Epidemiologist
Implement/improve infection control measures
Collect data regarding adherence and outcomes
Monitor healthcare-acquired infection rates
Investigate local outbreaks
Share daily reports with pharmacist
Isolation due to MDROs
Next, the Infection Control or Epidemiologist is responsible for READ SLIDE
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

36. Roles of the Team Members
IT/Data Manager
Establish method for obtaining data
Develop/adapt database to record interventions
Prepare annual reports for administrative arm
Aid in statistical analysis of program
*most programs lack this member and the pharmacist picks up the slack
The IT specialist or Data Manager READ SLIDE
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:

37. Performance Measures Essential in showing value of Stewardship program
Examples:
Antibiogram
Performed at least annually
Medication Use Evaluations (MUE)
Utilization/Purchasing Data quarterly
MDRO rates
Blood contamination Rates
Quality Measures
MUE– Levaquin ID in the ED

38. Can this be done at smaller hospitals?
120 bed hospital in Monroe, LA
ID MD, clinical PharmD, infection control, microbiologist
*paid MD and PharmD
Concurrent chart review 3 days/week (limited resources)
Study period = 1 year (all the way back in 2000)
Targeted patients
Multiple, prolonged, or high-cost antibiotics
Initial pushback from medical staff
69% recommendation acceptance
19% reduction in antibiotic expenditures (saved $177,000!)
LaRocco et al. CID 2003.
Now the common concern is often: Can this be done at smaller institutions? The answer is overwhelmingly YES.
An example success story is a 120-bed institution is Monroe, Louisiana that established an ASP with an ID physician, clinical pharmacist, infection control member, and a microbiologist member. Now that lineup isn’t the ideal team but it’s got its 2 core members and some help.
This team conducted chart review 3 times a week rather than every day over the course of a year, due to limited resources. They also focused their approach seeking out patients with multiple, prolonged, or high-cost antibiotics rather than attempting to employ all of the supplemental strategies outlined in the IDSA’s vision.
The result? While the team received initial pushback from the medical staff, 69% of their recommendations were ultimately accepted resulting in a 19% reduction in antibiotic expenses saving the institution $177,000.
Now that’s not a bad haul for having limited resources and sort of picking and choosing which parts of the ASP model to implement

39. Tier System Approach Raising awareness costs = $0
Different approaches for different budgets/personnel
Low-lying fruit
Start small, simple, and smart
Identify “Problem Child” units or antibiotics
Easy “wins”
Build ASP credibility
IV to PO Conversions; De-escalation of therapy; Pre-printed order sets
Raising awareness costs = $0
Improve the systems you already have in place
As evident by the previous example success story, there is a certain vision the IDSA has laid out for establishing an ASP but the fact is it can’t be executed all at once.
When beginning an ASP, each institution needs to employ a Tier System Approach. As with many things in life, ASPs are not “one size fits all” and it’s important that your individual institution start small and with a focused approach that is specific to the needs of your institution.
Many who are experts at establishing an ASP advocate identifying what is called the low-lying fruit. This translates to starting small – simple – and smart. Identifying the QUOTE Problem Child units or those you know always order too many antibiotics often double-covering or triple-covering when it’s not necessary, not imposing stop dates on antibiotics so the patients remain on broad spectrum or empiric therapy for weeks, etc.
Focus on Easy Wins or problems concerning antibiotic use that are obvious to you that can be fixed quickly. Last, identify areas of low-lying fruit that can quickly build your new ASPs credibility among pharmacy and medical staff so the program can gain support and momentum early on.
Raising awareness is free. This is where educating your peers in the pharmacy or on the medical team can help establish the need for an ASP. You can’t do it by yourself, you’ll need to rally support from others to get the program off the ground.
Last, improve the systems you already have in place. The easiest example that comes to mind is infection control. Revamp the policies your institution already has in place for hand-washing, isolation policies, gowns, gloves, etc. Reinforcing these policies can improve transmission and infection rates drastically free of charge. Re-educate staff why these policies are in place and why they are important to the patients’ health as well as their own health.

40. A Few Examples: Management of MDRO in Healthcare Settings
CDC’s 4 Principles:
1. Infection prevention
Catheters , VAP
2. Accurate and prompt diagnosis and treatment
Etiology of infectious process
3. Prudent use of antimicrobials
4. Prevention of transmission
Hand washing, isolation, etc.
CDC:
The next few slides will provide a few examples of strategies your ASP can target to achieve success. The CDC outlined some of these strategies in its 4 Principles in the Prevention of multi-drug resistant organisms in Healthcare Settings.
The Principles include:
Infection Prevention thru timely removal of catheters and ventilators as warranted in an effort to prevent hospital-acquired infections that are often very resistant.
Accurate and prompt diagnosis and treatment which involves properly identifying the cause and source of infection so that the appropriate antibiotic may be selected to treat the patient
Prudent use of antimicrobials which involves many of the same strategies employed in the IDSA’s vision of an ASP such as de-escalation and IV to PO conversion
And last Prevention of transmission which we just discussed. 40

41. A Few Examples: Restriction vs. Facilitation
Consider Facilitation vs. Restriction
The goal of an ASP is NOT to limit appropriate use of antibiotics
More restricted antibiotics = sicker patient usually is
More delay
More pushback from medical staff
Mixed signal of ASP
The only dose proven to save lives in the first one!
Allow according to restriction protocol, then adjust prn
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
An important strategy that needs to be considered in starting an ASP is Facilitation vs. Restriction. The last thing an ASP wants to do is delay care to the patient and possibly cause harm. Restriction can send the wrong message and the ASP may be done before it even gets started. However, many institutions successfully employ restrictive guidelines on a number of antimicrobial agents in an effort to prevent against the inappropriate prescribing of many antibiotics.
The argument of facilitation stems from the fact the concept that the only dose proven to save lives is the first dose – consistent with a strategy of facilitation, it’s often better to let the first dose of an antibiotic get to patient quickly followed by a review of the appropriateness of the therapy. An adjustment in antimicrobial therapy can then be made after the fact, followed by an educational intervention with the appropriate prescriber.

42. Many Available Resources
ASHP – ashp.org
IDSA – idsociety.org
CDC – cdc.gov
CID – cid.oxfordjournals.org
Available for purchase
Sanford Guide to Antimicrobial Therapy
Johns Hopkins ABX Guide
hopkins-abxguide.org
Establishing an ASP can initially be a daunting task but the good news is there’s a lot of help out there.
ASHP, IDSA, the CDC, and the Clinical Infectious Disease Journal are great partners in this endeavor. A wealth of information regarding ASPs and antibiotics can be accessed free of charge requiring no membership.
Affordable information sources that provide health care professionals with the latest information regarding antibiotics and resistance patterns include the Sanford Guide to Antimicrobial Therapy and the Johns Hopkins ABX Guide. Both are available in pocket-sized guides as well as apps for your wireless handheld devices. 42

43. ASP: Why now? 1. Antimicrobial overuse/misuse affects resistance
2. Antimicrobial resistance is at unprecedented levels
3. Typically financially self-supporting
Although this should be a secondary goal
4. It’s the RIGHT THING TO DO
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
But why now? Aren't we in the worst recession since the Great Depression? Yes we are and budgets are tight but something must be done and we're the ones who can do it.
Antibiotics are terribly overused and misused. It's been estimated that half of all antibiotic use is unnecessary
Antibiotic resistance is at unprecedented levels and drugs to treat these resistant organisms are really drying up. Think of it as the mid-2000s and all is well in the housing market. If only we KNEW the problem ahead of time and had the tools to fix it, we wouldn't be in this mess.
If that's not convincing, then argument #3 should resonate a bit. ASPs typically pay for THEMSELVES. There's no better music to your financial administrator's ears than hearing you say you're proposing to establish a new program to help save lives and money.
And last, when it comes down to it, forming a program like this is just the right thing to do. We all pursued health care for the purpose of preserving life and there's no doubt a program like an ASP can improve clinical outcomes.

44. What is the status of ASP in your institution?
Question posed by speaker at ASHP Midyear Meeting 2010
10% No ASP, no plans to pursue one
20% No ASP, need to establish one
30% Currently discussing need for an ASP
20% The ASP we have is not very effective
20% The ASP we have is highly regarded
So if you don’t have an ASP, you’re not alone but you may be soon
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
That said, many institutions have already established or are currently in the process of establishing an ASP. California actually MANDATES it.

45. Barriers to Establishing ASPs
1. Lack of funding
ASPs often function in personnel’s spare time initially
2. Shortage of adequately-trained ID MDs and Pharmacists
3. Lack of pharmacy leadership support
4. MD autonomy
5. Competition for funding
Money is going to go to programs that are mandated
6. Antagonistic colleagues
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
Owens RC, Shorr AF, Deschambeault AL. Antimicrobial stewardship: shepherding precious resources. Am J Health-Syst Pharm. 2009; 66(Supp 4):S15-22
That said, you’ll surely encounter a number of barriers when establishing an ASP and this really goes for establishing any new program.
The most common barriers involve
Lack of funding
Shortage of adequate-trained ID physicians and ID pharmacists
Lack of pharmacy leadership support
Physician autonomy
Competition for funding
Antagonistic colleagues
Many of these are commonly seen during the implementation of any new program but be sure to check out the resources provided in this presentation to help overcome these barriers and forge the way for a successful ASP in your institution.

46. Building your Case
1. Current situation is likely costing institution unnecessary dollars
2. Clinical issues make timely program implementation compelling
3. A formal business plan is essential
4. Need to demonstrate return on investment (ROI) over a reasonable time period
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
So hopefully by this point you’re onboard and motivated. Now that you have a little background information on ASPs and are up to date on the many tools available, you’re probably wondering “how do I actually implement an ASP at my institution?”
The answer is – you need to build your case and present it to the appropriate body and that might be the pharmacy director initially followed by the financial administrators of your hospital depending how your institution is set up.
It’s imperative that arm yourself with the information in the resources available to you through this presentation, subsequent presentations, and other sources. Once you’ve done that or even while you’re doing that – seek out team members who are interested in helping or at least supportive of the initiative. Remember the positive results of ASPs cannot be accomplished unilaterally. This also means that you need to seek out those outside the pharmacy walls who can help build your case. Remember the core members of an ASP are a pharmacist and a physician champion. Historically, the only instances in which ASPs have struggled or stalled out are when there is not a physician on board.

47. Conclusion: Baby Steps
Avoid making cost-reduction your #1 goal
Educate personnel on ASP Basics
Identify glaring problem areas and establish areas of improvement
Work on multidisciplinary development of evidence-based guidelines
Based on national guidelines, tailored to institution based on resistance patterns
Work to ensure de-escalation and antibiotic stop dates
Improve efficiency of pharmacy distribution system
Facilitation vs. Restriction
ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
An Antimicrobial Stewardship Program is established in baby steps.
READ SLIDE

48. Conclusion: Needs identified by IDSA in 2011 publication
National Funding
Legislative action
Research and Development
ASPs
Novel Antibiotics
Resistance, especially as it relates to MDROs
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: /cid/cir153
Earlier this year, the IDSA published a white paper detailing what it believes is the necessary action needed at all levels of authority to accomplish the goals of the Antimicrobial Stewarship Program. At the core of its argument are National Funding, Legislative Action, and Research and Development. A link to this paper has been provided at the bottom of the slide.

49. ASP Resources Online Webinars ASP-specific Websites
ASP-specific Websites
Nebraska Medical Center
Univ. of Kentucky
Univ. of Pennsylvania
That concludes the presentation on Antimicrobial Stewardship Programs: The Basics. Thank you for your attention and I invite you to visit the Pharmacy Systems Resource Center for more information, links, and webinars related to this presentation.
Goff, DA. ASHP Advantage Newsletter. CE in the Mornings. Working Together: Implementing Interdisciplinary Antimicrobial Stewardship Programs. March 2010.

50. Questions?