Download MDRO Treatment Options

Antimicrobial Stewardship
David Meyer, PharmD
Clinical Pharmacy Manager
Fairmont General Hospital
Objectives

Identify types of antimicrobial resistance
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Discuss multi-drug resistant organisms and
possible treatment options
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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
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Enzyme Inactivation
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-lactamase production
ESBL production
Carbapenemase
New Delhi Metallo- -lactamase
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Examples:
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E. coli producing -lactamase or ESBL
Klebsiella producing carbapenemase
Antimicrobial Resistance:
Mutation & Selection/Acquired Resistance
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Alteration of the target site
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Altered protein binding
Altered DNA enzymes
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Examples:
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MRSA – methicillin-resistant Staph. aureus
PBP (Penicillin binding protein)-resistant Strep. pneumo
Ciprofloxacin resistance in Mycobacterium
Antimicrobial Resistance:
Mutation & Selection/Acquired Resistance
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Decreased access to the target site
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Efflux pumps - Antimicrobial is pumped out of the
bacteria before it accumulates
Altered structure of outer membrane proteins or porins
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Example:
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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)
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Prevalent in hospitals & long-term care facilities
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Not as likely to cause disease in LTCF (colonization)
Cause the same infections as non-MDROs BUT
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Fewer antibiotic choices
Isolation
Increased length of stay
Increased risk of ADE
Increased mortality
= Increased $$$
MDRO Treatment Options:
Community-acquired MRSA (Ca-MRSA)
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Transmission
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Contaminated hands
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Skin-to-skin contact
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Crowded conditions
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Poor hygiene
Increased risk
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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
MDRO Treatment Options:
Community-acquired MRSA (Ca-MRSA)
**Use varies greatly by site of infection, refer to IDSA MRSA Guidelines 2011**
Mild-moderate infection
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Doxycycline or Minocycline
 Caution with susceptibility tests
Clindamycin
Trimethoprim/Sulfamethoxazole
Severe infection
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Vancomycin - PREFERRED
Daptomycin (NOT for pneumonia)
Linezolid (pneumonia)
Dalfopristin/Quinupristin
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Limited by ADE arthralgias
Tigecycline (cSSTI, intra-ab)
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Low serum concentrations
Telavancin (cSSTI)
Ceftaroline (cSSTI)
*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/cir153
Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
MDRO Treatment Options:
Penicillin-Resistant Strep. Pneumoniae (PRSP)
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Causes respiratory tract infections and meningitis
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Resistant to:
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Penicillin G
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*due to alteration in penicillin-binding proteins (PBPs)
Variable resistance to cephalosporins, macrolides, tetracyclines,
clindamycin
Alternatives:
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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)
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Usually Enterococcus faecium
Resistant to:
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Vancomycin, Aminoglycosides, Penicillins, Quinolones
Treatment options:
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Linezolid
Quinupristin/dalfopristin
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Faecium only
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Combination therapy recommended
Tigecycline
Daptomycin
Site Specific– Urinary Tract Infections
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Nitrofurantoin
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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
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Resistant to:
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Meropenem, Imipenem
Alternatives:
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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
Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416
Antimicrob Agents Chemother. 2008 October; 52(10): 3795–3800
Livermore DM. Clin Infect Dis 2002;34:634-40
Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
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
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34% of ESBL-producing isolates from patients with no recent
health care contact
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Ben-Ami R et al. Clin Infect Dis 2009;49:682-90
MDRO Treatment Options:
ESBL-producing Organisms
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Most commonly Klebsiella or E.coli
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Resistant to:
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2nd/3rd generation Cephalosporins
Aztreonam
Aminoglycosides
Fluoroquinolones
Alternatives:
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Carbapenems (some emerging resistance)
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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
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KPC = CRE
Most commonly Klebsiella or E.coli
NDM-1 found in water samples in India
Resistant to:
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All Carbapenems
Aminoglycosides
Fluoroquinolones
Alternatives:
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Tigecycline
Colistin
MDRO Treatment Options:
Acinetobacter
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Up and coming “superbug”
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Found in soil and water
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Can live on skin &
surfaces for days
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Predominately a colonizing
organism
MDRO Treatment Options:
Acinetobacter
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Therapy:
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ID Consult!
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Agents:
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Carbapenems (building resistance as of 2005)
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Ampicillin/sulbactam +/- Meropenem
Tigecycline - in combination only (e.g. + Amikacin)
Polymyxin B + Imipenem/cilastatin + Rifampin
Colistin
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Susceptibility 32% to >90%
Susceptibility 55% to >80%
Other treatment therapies and combinations but
Acinetobacter infections very MDRO: Mortality 20-50%
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
Gilbert DN, et al. Sanford Guide to Antimicrobial Therapy 2011, 41st ed.
Am J Respir Crit Care Med ; 2005 ; 171 : 388 -416
Antimicrobial Stewardship
http://www.hhnmag.com/hhnmag/gateFold/PDF/05_2012/HHN_May2012Cover.pdf
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
Antimicrobial Stewardship –
Why?
Not much in the pipeline
Boucher et al. Clin Inf Dis 2009
World Health Organization
(WHO) 10 x ’20 Initiative
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Published in early 2010
by IDSA
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WHO identified
antimicrobial resistance
as a major issue
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153
Clin Infect Dis 2010;50:1081-83.
Antimicrobial Stewardship Programs
(ASP)
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Plethora of literature on resistance and ASP
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Refer to local Antibiograms for most accurate resistant patterns
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leadstewardship.org and ASHP Educational
Webinars under Infectious Diseases subsection
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Existing Webinars
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Summarize IDSA Guidelines (2007)
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ASP-supportive literature
Success stories
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http://cid.oxfordjournals.org/content/44/2/159.full
Personal & in literature
Our focus: Key points, focused approach, resources
Purpose
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Optimize clinical outcomes
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Minimize unintended consequences of
antimicrobial use
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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
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Core Strategies
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Prospective audit with intervention and feedback
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Formulary restriction with pre-authorization
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Looking at antibiotic orders as they come, adjusting per pre-set guidelines
UKMC: negative impact (let first dose go thru, intervene after)
Supplemental Strategies
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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 Institution
http://www.ashpmedia.org/symposia/4cpe/stewardship/
CDC: Methods to Improve
Antimicrobial Use
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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
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Multidisciplinary problem that cannot be solved by
one person
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Core members (eventual compensation is ideal)
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ID MD
ID Pharmacist
Adjunct members
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Microbiologist
IT/Data Specialist
Infection Control Professional and/or Epidemiologist
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
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Physician Champion
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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
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
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Clinical Pharmacist
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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
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
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Microbiologist
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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;44:159-77.
Roles of the Team Members
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Infection Control and/or Epidemiologist
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Implement/improve infection control measures
Collect data regarding adherence and outcomes
Monitor healthcare-acquired infection rates
Investigate local outbreaks
Share daily reports with pharmacist
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Isolation due to MDROs
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Roles of the Team Members
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IT/Data Manager
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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
2007 IDSA ASP Guidelines: Dellit TH. Clin Infect Dis 2007;44:159-77.
Performance Measures
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Essential in showing value of Stewardship program
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Examples:
 Antibiogram
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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?
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120 bed hospital in Monroe, LA
ID MD, clinical PharmD, infection control, microbiologist
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*paid MD and PharmD
Concurrent chart review 3 days/week (limited resources)
Study period = 1 year (all the way back in 2000)
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Targeted patients
 Multiple, prolonged, or high-cost antibiotics
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Initial pushback from medical staff
69% recommendation acceptance
19% reduction in antibiotic expenditures (saved $177,000!)
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LaRocco et al. CID 2003.
Tier System Approach
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Different approaches for different budgets/personnel
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Low-lying fruit
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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
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Raising awareness costs = $0
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Improve the systems you already have in place
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: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf
A Few Examples:
Restriction vs. Facilitation
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Consider Facilitation vs. Restriction
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The goal of an ASP is NOT to limit appropriate use
of antibiotics
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More restricted antibiotics = sicker patient usually is
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More delay
More pushback from medical staff
Mixed signal of ASP
The only dose proven to save lives in the first one!
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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
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ASHP – ashp.org
IDSA – idsociety.org
CDC – cdc.gov
CID – cid.oxfordjournals.org
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Available for purchase
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Sanford Guide to Antimicrobial Therapy
Johns Hopkins ABX Guide
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hopkins-abxguide.org
ASP: Why now?
1. Antimicrobial overuse/misuse affects resistance
2. Antimicrobial resistance is at unprecedented levels
3. Typically financially self-supporting
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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:
http://www.ashpmedia.org/symposia/4cpe/stewardship/
What is the status of ASP in your institution?
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Question posed by speaker at ASHP Midyear Meeting 2010
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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
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So if you don’t have an ASP, you’re not alone but you may be soon
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ASHP Midyear 2010 – Antimicrobial Stewardship: Building the Case and Overcoming Barriers in your Institution:
http://www.ashpmedia.org/symposia/4cpe/stewardship/
Barriers to Establishing ASPs
1. Lack of funding
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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
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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:
http://www.ashpmedia.org/symposia/4cpe/stewardship/
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
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Avoid making cost-reduction your #1 goal
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Educate personnel on ASP Basics
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Identify glaring problem areas and establish areas of improvement
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Work on multidisciplinary development of evidence-based guidelines
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Based on national guidelines, tailored to institution based on resistance patterns
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Work to ensure de-escalation and antibiotic stop dates
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Improve efficiency of pharmacy distribution system
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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
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National Funding
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Legislative action
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Research and Development
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ASPs
Novel Antibiotics
Resistance, especially as it relates to MDROs
Clin Infect Dis. (2011) 52 (suppl 5): S397-S428. doi: 10.1093/cid/cir153
ASP Resources
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Online Webinars
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http://www.ashp.org/menu/Education/OnlinePrograms.aspx
http://leadstewardship.org/activities.php
ASP-specific Websites
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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?