antimicrobial stewardship david meyer, pharmd clinical pharmacy manager fairmont general hospital

Antimicrobial Stewardship

David Meyer, PharmDClinical Pharmacy ManagerFairmont General Hospital

Objectives

Identify types of antimicrobial resistance

Discuss multi-drug resistant organisms and possible treatment options

Describe the basic framework of an antimicrobial stewardship program

Antimicrobial Resistance

Clin Infect Dis. (2011) 52 (suppl 5): S397-S428.

Antimicrobial Resistance:Selective Pressure

Mulvey M R , Simor A E CMAJ 2009;180:408-415

Antimicrobial Resistance:Mechanisms of genetic resistance to antimicrobial agents

Coates A et al. Nature Reviews Drug Discovery 1, 895-910 (November 2002)

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


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


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

Examples of Common Resistant Bugs

CMAJ February 17, 2009 vol. 180 no. 4 408-415

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 $$$

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

Clinical Microbiology Reviews, July 2010, p. 616-687, Vol. 23, No. 3

Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153

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)

**Use varies greatly by site of infection, refer to IDSA MRSA Guidelines 2011**

*Adjuncts: rifampin (also in combo with FQs), gentamicin, beta-lactams

Clinical Microbiology Reviews, July 2010, p. 616-687, Vol. 23, No. 3

Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

MDRO Treatment Options: Community-acquired MRSA (Ca-MRSA)

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

Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

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

CMI 16:555,2010 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

Clin Infect Dis. (2010) 51 (1): 79-84 http://emedicine.medscape.com/article/216993-treatment

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

Lister PD, Wolter DJ Clin Infect Dis 2005;40:S105-114 Livermore DM. Clin Infect Dis 2002;34:634-40Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.Antimicrob Agents Chemother. 2008 October; 52(10): 3795–3800

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

Ben-Ami R et al. Clin Infect Dis 2009;49:682-90

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

Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416 Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

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

MDRO Treatment Options: Acinetobacter

Up and coming “superbug”

Found in soil and water

Can live on skin & surfaces for days

Predominately a colonizing organism

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%

MDRO Treatment Options: Acinetobacter

Landman D et al. Arch Intern Med 2002;162:1515-20 Kopterides P et al. Int J Antimicrob Agents 2007;30:409-14

Clin Infect Dis. (2010) 51 (1): 79-84 Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.

Antimicrobial Stewardship

http://www.hhnmag.com/hhnmag/gateFold/PDF/05_2012/HHN_May2012Cover.pdf

IDSA Definition

Antimicrobial Stewardship is an activitythat promotes:

– The appropriate selection of antimicrobials.– The appropriate dosing of antimicrobials.– The appropriate route and duration of antimicrobial therapy.

What is an Antimicrobial Stewardship Program (ASP)

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

Antimicrobial Stewardship – Why?

Boucher et al. Clin Inf Dis 2009

Not much in the pipeline

World Health Organization (WHO) 10 x ’20 Initiative

Published in early 2010 by IDSA

WHO identified antimicrobial resistance as a major issue


Clin Infect Dis 2010;50:1081-83.

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)

http://cid.oxfordjournals.org/content/44/2/159.full ASP-supportive literature Success stories

Personal & in literature

Our focus: Key points, focused approach, resources

Purpose

Optimize clinical outcomes

Minimize unintended consequences of antimicrobial use Toxicity Selection of pathogenic organisms (e.g. C. diff) Emergence of resistance

2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.

ASP Guidelines Core Strategies 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)

2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.ASHP Midyear 2010 CE Presentation – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institutionhttp://www.ashpmedia.org/symposia/4cpe/stewardship/

CDC: Methods to Improve Antimicrobial Use

Passive prescriber education Standardized order forms Formulary restrictions Pre-authorization Pharmacy substitution Multidisciplinary DUE Performance feedback CPOE

CDC: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf

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: http://www.ashpmedia.org/symposia/4cpe/stewardship/

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


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



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



Microbiologist Provides surveillance data for Antibiogram Develops combination antibiotic Antibiograms Reviews current diagnostic tests and investigates

pros and cons of incorporating new, novel tests



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



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


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

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.

Tier System Approach

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

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: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf

A Few Examples:Management of MDRO in Healthcare Settings

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:http://www.ashpmedia.org/symposia/4cpe/stewardship/

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

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


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:

http://www.ashpmedia.org/symposia/4cpe/stewardship/

Barriers to Establishing ASPs1. 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


Owens RC, Shorr AF, Deschambeault AL. Antimicrobial stewardship: shepherding precious resources. Am J Health-Syst Pharm. 2009; 66(Supp 4):S15-22

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:http://www.ashpmedia.org/symposia/4cpe/stewardship/

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:

http://www.ashpmedia.org/symposia/4cpe/stewardship/

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


ASP Resources

Online Webinars http://www.ashp.org/menu/Education/OnlinePrograms.aspx http://leadstewardship.org/activities.php

ASP-specific Websites Nebraska Medical Center

www.nebraskamed.com/asp Univ. of Kentucky

www.hosp.uky.edu/pharmacy/AMT/default.html Univ. of Pennsylvania

www.uphs.upenn.edu/bugdrug

Goff, DA. ASHP Advantage Newsletter. CE in the Mornings. Working Together: Implementing Interdisciplinary Antimicrobial Stewardship Programs. March 2010.

Questions?

antimicrobial stewardship david meyer, pharmd clinical pharmacy manager fairmont general hospital

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