1. education

Antimicrobial Stewardship
CHS Pharmacy Education Series
2015 Pharmacy Education Series
March 18, 2015
Antimicrobial Stewardship
A
ti i bi l St
d hi
Featured Speakers:
Jessica Robinson, PharmD, BCPS
Alan Gross, PharmD, BCPS
Assistant Professor
Infectious Diseases Clinical Pharmacy Specialist
University of Charleston School of Pharmacy
Infectious Diseases Pharmacist
University of Illinois Hospital and Health Sciences
Clinical Assistant Professor
University of Illinois at Chicago, College of Pharmacy
1
Online Evaluation, Self-Assessment
and CE Credit
 Submission
Submission of an online evaluation is the only way to obtain CE credit of an online evaluation is the only way to obtain CE credit
for this webinar
 Go to www.ProCE.com/CHSRx
 Webinar attendees will also receive an email with a direct link to the web page
 Print your CE statement of completion online
– Credit for live or enduring only
 Deadline: April 17, 2015
 CPE Monitor (applicable to pharmacists)
(
l bl
h
)
– CE information automatically uploaded to NABP/CPE Monitor within 1 to 2 weeks of the completion of the self‐assessment and evaluation
Event Code
Code will be provided at the end of today’s activity ProCE, Inc.
www.ProCE.com
2
1
Antimicrobial Stewardship
CHS Pharmacy Education Series
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Antimicrobial Stewardship
CHS Pharmacy Education Series
March 18, 2015
Antimicrobial Stewardship
Featured Speakers:
Jessica Robinson, PharmD, BCPS
Alan Gross, PharmD, BCPS
Assistant Professor
Infectious Diseases Clinical Pharmacy Specialist
University of Charleston School of Pharmacy
Infectious Diseases Pharmacist
University of Illinois Hospital and Health Sciences
Clinical Assistant Professor
University of Illinois at Chicago, College of Pharmacy
It is the policy of ProCE, Inc. to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Dr. Gross has no relevant commercial and/or financial relationships to disclose. Dr. Robinson has no relevant commercial and/or financial relationships to disclose.
Please note: The opinions expressed in this activity should not be construed as those of the CME/CE provider. The information and views are those of the faculty through clinical practice and knowledge of the professional literature. Portions of this activity may include unlabeled indications. Use of drugs and devices outside of labeling should be considered experimental and participants are advised to consult prescribing information and professional literature.
5
CE Activity Information & Accreditation
ProCE, Inc. (Pharmacist CE)
– 2.0 contact hours
Funding:
This activity is self‐funded
This activity is self
funded through CHSPSC.
through CHSPSC
6
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Antimicrobial Stewardship
p
Trent A. Beach, PharmD, MBA, MHA, BCPS, FASHP, FACHE
Corporate Director Clinical Pharmacy
Corporate Director, Clinical Pharmacy Community Health System Professional Services Corporation, Franklin, Tennessee 7
Introductory Objectives
 Discuss CHSPSC initiative to meet antimicrobial stewardship
practice standards in affiliated hospitals
 Describe interdisciplinary collaboration across the network
 Discuss the CHSPSC tiered-assessment approach on
antimicrobial stewardship (ASP)
 Discuss metrics in place and under development
 Locate resources available to support ASP implementation or
expansion
p
((e.g.,
g , tier p
progression)
g
)
 Training and educational availability
8
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHSPSC ASP Initiative
Project Goals
• Implement new or enhance existing antimicrobial stewardship
programs consistent with CDC Core Elements at Community
Health Systems (CHS)-affiliated facilities
• Improve antimicrobial use
• Reduce antimicrobial drug
g expenditure
p
from inappropriate
pp p
and/or unnecessary antimicrobial use
• Increase education and knowledge surrounding antimicrobial
stewardship
9
CHSPSC ASP Initiative
Project Objectives
• Increase the number of sites with core antimicrobial stewardship elements
• Increase the number of sites with enhanced antimicrobial stewardship
elements
• Increase pharmacist documentation of antimicrobial stewardship activities
• Increase and expand use of decision support tools
• Decrease measures of antimicrobial use
• Decrease antimicrobial expenditure
• Increase the number of pharmacists with antimicrobial stewardship
certification
• Conduct ongoing corporate antimicrobial site education and communication
• Increase the number of pharmacist competencies pertaining to infectious
diseases and antimicrobial stewardship
• Conduct baseline competency assessment for pharmacists in antimicrobial
stewardship
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Antimicrobial Stewardship
CHS Pharmacy Education Series
ASP Initiative Interdisciplinary Scope
Role
Project Lead
Project Sponsor
Project Core Team
Key Stakeholders
Name
Vacant,
Trent Beach (Interim)
Trent Beach
Vacant,
Trent Beach (Interim)
ASP Task Force
Bob Fink
Lynn Simon
Mike Miserocchi
K Fl
Ken
Flood
d
Sandy Carson
Nicolas Abella
Title
Corporate Director,
Director ASP
Corporate Director, Clinical Pharmacy
Corporate Director, ASP
Physicians and Clinical Pharmacists
Pharmacy Executive
Quality and Clinical Services Executive
Clinical Services Executive
Mi bi l
Microbiology
S i Director
Senior
Di
Infection Prevention Director
Medical/Surgical Nursing Director
11
ASP Task Force







Brooke Gabel, PharmD, Bayfront Health St Petersburg
Vanessa Gray,
y, PharmD,, Trinityy Medical Center,, Birmingham
g
David Lourwood, PharmD, Poplar Bluff Regional
Thao Nguyen, PharmD, Northwest Medical Center
Penny Watkins, PharmD, Physicians Regional Medical Center
Kevin Shea, MD, Carolinas Hospital System
Adding
g other advisors
12
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Antimicrobial Stewardship Program Baseline Assessment: PPMI SURVEY RESULTS
13
Pharmacy Practice Model Initiative (PPMI) Survey
Results: All CHS Hospitals

2014 PPMI Surveys were sent out to all CHS facilities  2‐part survey:  PPMI assessment PPMI assessment
 Antimicrobial stewardship (ASP) baseline assessment

Antimicrobial stewardship survey questions:  Leadership support  Multidisciplinary core team support  Antimicrobial interventions: physicians and/or pharmacists p y
p
 Antibiotic usage and outcome measures  Antibiotic resistance pattern monitoring  Pharmacy–driven interventions (policy & protocols) 14
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Pharmacy Practice Model Initiative (PPMI) Survey
Results: All CHS Hospitals
LEADERSHIP SUPPORT Programs
Yes
No Total Formal ASP
37.4% (71) 62.6% (119) 190
RPh Leader for ASP
78.8% (56)
21.1% (15) 71 MD Leader for ASP 59.1% (42)
40.8% (29) 71
Written ASP Charter 33.8% (24)
( )
66.2% (47) ( )
71 22.5% (16) 71
MULTIDISCIPLINARY CORE TEAM SUPPORT ASP core members from multidisciplinary team 77.4% (55)
15
Pharmacy Practice Model Initiative (PPMI) Survey
Results: All CHS Hospitals
INTERVENTIONS Programs
Yes
No Total Approval of specific antibiotics by MD or RPh Approval
of specific antibiotics by MD or RPh
prior to dispensing 41 5% (78)
41.5% (78) 58 5% (110)
58.5% (110) 188
Usage criteria for specific antibiotics 56.1% (105) 43.9% (82) 187
MD or RPh review course of specific antibiotics
72.3% (136) 27.7% (52) 188 MD or RPh chart review for specific conditions
58.5% (110) 41.5% (78) 188
PHARMACY‐DRIVEN INTERVENTIONS
PHARMACY‐DRIVEN INTERVENTIONS
IV to PO protocol auto‐performed 89.9% (134)
10.1% (15)
149
Renal dosing protocol auto‐performed
92.9% (158)
7.1% (12)
170
TDM protocol auto‐performed
95.3% (162)
4.7% (8)
170 16
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Pharmacy Practice Model Initiative (PPMI) Survey
Results: All CHS Hospitals
ANTIBIOTIC USAGE AND OUTCOMES MEASURES Programs
Yes
Annual review of antimicrobial formulary 76.4% (143) 23.5% (44) 187
No Total Annual review of antimicrobial usage data 68.6% (129) 31.4% (59) 188
ANTIBIOTIC RESISTANCE PATTERN Annual review of antibiogram 95.2% (179) 4.8% (9) 188
Annual antibiogram production & distribution
97.3% (183) 2.7% (5) 188 17
Antimicrobial Stewardship Program Baseline Assessment: DATA ANALYSIS 18
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Pharmacy Practice Model Initiative (PPMI) Survey
Results: Scoring System
 In order to assess individual facility’s efforts for ASP, a scoring system was established
 Scores are assigned based on the importance of each ASP core element
Classification Scoring Criteria Points assigned 4
4
4
Formal ASP RPh Leader for ASP MD Leader for ASP Leadership Support Multidisciplinary Core Team ASP Core members from multidisciplinary team Usage criteria for specific abx Restricted abx (MD/RPh prior to dispensing) Interventions MD/RPh review course of specific abx MD/RPh review patients with specific conditions
MD/RPh review patients with specific conditions
Antibiotic Usage and Outcomes measures
1
1
2
2
2
Annual review of antimicrobial formulary 3
Annual review of antimicrobial utilization data 3
Antibiotic resistance pattern Facility has antibiogram Pharmacy protocols 2
If they have ONE of the IV to PO/Renal Dosing/TDM
protocols and perform intervention automatically 1 per each
protocol
Total Score: 31 points19
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Pharmacy Practice Model Initiative (PPMI) Survey
Results: Scoring System
CATEGORY
SCORES
ANTIMICROBIAL STEWARDSHIP PROGRAM
A 25 – 31 Currently have a more advanced ASP in place
B 16 – 24 Currently have ASP in place
C C
8 – 15 D
0 – 7 TIER
Tier 2 ‐ 3
Tier 1 ‐ 2
Have partial tier 1 in place, assess for tier 1 approach and to for
tier 1 approach and to
supplement any education/needed Tier 1 Currently does not have ASP or ASP‐like activities in place May require further assistance
20
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Antimicrobial Stewardship
CHS Pharmacy Education Series
ASP Tiered Approach

To guide antimicrobial stewardship program implementation and enhancement, a three‐tier assessment system has been designed

Elements within each tier represent key components from national guidelines and recommendations:  CDC Antimicrobial Stewardship Core Elements  IDSA 2007 Guideline for ASP Development 21
Antimicrobial Stewardship Tier System: Tier 1
CDC Core Element
Parameter
Description
Leadership Support
ASP policy/procedure adopted  Policy outlines program structure
Accountability Physician leader for ASP
 Physician leader identified Drug Expertise Pharmacist leader for ASP  Pharmacist leader identified Multidisciplinary core team ASP committee, team, workgroup  Group meets on routine basis in place
Actions to support optimal Pharmacy‐driven protocols antimicrobial use
 IV to PO conversion  PK/PD dosing/monitoring
Antibiotic usage tracking Drug utilization data monitored
by ASP team  DDD and/or DOT  Antibiotic expenditure
Antimicrobial use and resistance reporting Information reported routinely to
staff to improve abx use
 Sentri7® number of interventions
 Evidence of improvement Antibiotic resistance pattern tracking Antibiogram prepared and reported using CLSI guideline
 Prepared annually  Data reviewed by ASP team
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11
Antimicrobial Stewardship
CHS Pharmacy Education Series
Antimicrobial Stewardship Tier System: Tier 2
CDC Core Element
Parameter
Description
Accountability/Drug Expertise Physician leader for ASP Pharmacist leader for ASP
 ID trained physician  Pharmacist with post‐graduate ID t i i
ID training Actions to support optimal antimicrobial use
Interventions that target initiation of therapy  ≥1 intervention in place  Order sets, clinical pathways or guideline, usage criteria Post‐prescriptive review of antimicrobial  Targeted antimicrobial review within 72 hours  Drug‐bug mismatch Interventions targeting
microbiology reporting
microbiology reporting  Selective reporting (e.g., AmpC organisms carbapenems when
organisms, carbapenems when
organisms sensitive to cefepime)
Antimicrobial use and resistance reporting Tracking key MDROs, review  C. diff
by ASP team regularly  Carbapenem‐resistance Enterobacteriaceae Education
Regular antimicrobial stewardship education provided
 Education sessions on improving antimicrobial use 23
Antimicrobial Stewardship Tier System: Tier 3
CDC Core Element
Parameter
Description
Actions to support optimal antimicrobial use
Enhanced interventions targeting initiation of therapy  Antimicrobial indications  Restricted antibiotics requiring MD/RPh approval
approval Interventions targeting
appropriate diagnostics  Protocols on appropriate ordering of cultures and/or other diagnostics Interventions to optimize duration of therapy  Automatic stop orders for targeted antimicrobials  Duration of therapy requirement in orders Rapid diagnostics  MALDI‐TOF  PNA fish Antimicrobial use and resistance reporting Prescriber adherence monitored /clinician‐specific
prescribing data reported
 Adherence to ASP protocols, clinical pathways  Feedback/education to clinicians’ prescribing behavior
Education
ASP team education to other committees, taskforces
 Quality improvement, medication safety council, P&T committees
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Plan Metrics
Measure
Category
Data Required
Outcomes
Clinical
LOS, mortality, return visits
AMS-specific interventions Process
improvements
Interventional reports (e.g., IV2PO,
Streamlining, other)
Antibiotic Cost/APD
Financial
Cardinal Spend and APD by facility
DDD targeted
antimicrobials
Financial
Cardinal Spend (surrogate for
utilization)
Antimicrobials
administered timely for
sepsis
Education
STOP Sepsis Collaborative reports
Antibiogram/Resistance
Patterns
Longitudinal
Antibiogram Analytics
25
CHS Antimicrobial Stewardship Metrics Review
Fiscal Years 2013 and 2014
26
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHS FY 2013 – 14 Total Antibiotic Costs per Adjusted
Pharmacy Patient Day: CHS Legacy vs. CHS14
Total Antibiotic Costs per Adjusted Pharmacy Patient Day
$14.00
$11.98
$11.93
$
$12.00
Total An
ntibiotic Costs per APPD ($/day)
$10.00
$11 70
$11.70
$11.35
$10.67
$10.58
$10.44
$10.40
$9.51
$9.12
$8.77
$9.50
$8.50
$8.21
$7.79
$8.00
$7.74
$8.15
$8.30
$8.10
$7.87
$7.65
$7.41
$7.14
$6.97
$6.00
Combined
$4.00
CHS 14
$2.00
Legacy
$Q1 2013
Q2 2013
Q3 2013
Q4 2013
Q1 2014
Q2 2014
Q3 2014
Q4 2014
Quarters
27
CHS FY 2014 Antibiotic Costs per APPD
BY DIVISION
28
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHS FY 2014 Antibiotic Costs per APPD – by Division
Total Antibiotic Costs per APPD Average by Quarters
$12.0
$11.3
$10.4
Totall Antibiotic Costs per APPD Average ($/day)
$10.1
$10.0
$9.4
$9.3
$8.5
$8.9
$8.6
$8.4
$9.9
$9 8
$9.8
$9.0
$8.7
$7.8 $8.0
$8.0
$9 7
$9.7
$9.6
$9.2
$8.7
$8.0 $7.8
$7.6
$8.3
$7.1
$6.0
$4.0
$2.0
$0.0
Q1 2014
Q2 2014
Q3 2014
Q4 2014
Quarters
Division 1 Division 2
Division 3 Division 4
Division 5
Division 6
29
CHS FY 2014 Antibiotic Costs per APPD – Division 1
Average Total Antibiotic Costs per APPD ($/day)
A
FY 2014 Average Total Antibiotic Costs per APPD
$25.00
$20.00
Facility Data
FY 2014 Median
+1 Standard
Deviation
-1
1 St
Standard
d d
Deviation
$15.00
$10.00
$5.00
$-
30
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHS FY 2014 Antibiotic Costs per APPD – Division 2
FY 2014 Average Antibiotic Costs per APPD
$35.00
Averrage Antibiotic Costs per APPD ($/day)
Facility Data
$30.00
FY 2014 Median
+1 Standard
St d d Deviation
D i ti
$25.00
-1 Standard Deviation
$20.00
$15.00
$10.00
$5.00
$-
31
CHS FY 2014 Antibiotic Costs per APPD – Division 3
FY 2014 Average Antibiotic Costs per APPD
$25.00 Facility Data
FY2014 Median
Average Antibiotic Costs per APPD ($/day)
+1 Standard Deviation
$20 00
$20.00 ‐1 Standard Deviation
$15.00 $10.00 $5.00 $‐
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHS FY 2014 Antibiotic Costs per APPD – Division 4
FY 2014 Average Antibiotic Costs per APPD
$30.00
Facility Data
FY2014 Median
Average A
Antibiotic Costs per APPD ($/da
ay)
$25.00
+1 Standard Deviation
-1 Standard Deviation
$20.00
$15.00
$10.00
$5.00
$-
33
CHS FY 2014 Antibiotic Costs per APPD – Division 5
Total Av
verage Antibiotic Costs per APP
PD ($/day)
FY 2014 Total Antibiotic Costs per APPD
$25.00
Facility Data
FY2014 Median
$20.00
+1 Standard Deviation
-1 Standard Deviation
$15.00
$10.00
$5.00
$-
34
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Antimicrobial Stewardship
CHS Pharmacy Education Series
CHS FY 2014 Antibiotic Costs per APPD – Division 6
Average Total Antibiotic Costs per AP
PPD ($/day)
FY 2014 Average Total Antibiotic Costs per APPD
$18.00
Facility Data
$16.00
FY 2014 Median
$14.00
+1 Standard Deviation
-1 Standard Deviation
$12.00
$10.00
$8.00
$6.00
$4.00
$2.00
$-
35
Online Resource Location
36
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Online Resources

Overview Slide Deck by the Med/Srg Advisory
Council Antimicrobial Stewardship
p Team))


AMS Gap Analysis Checklist
Antimicrobial Stewardhip CE Webinar Recording
by Dr’s Shea and Davis, Carolinas Hospital
System – Accredited for CE for Physicians, Nurses,
and Pharmacists


Key Aspects of a Successful AMS References

Example Objectives (Payson Regional Medical
Center)

IV to PO Conversion Guidelines
Example Successful AMS Programs in
Community Hospitals
37
Online Resources
Category
Document Name
Antibiogram
Antibiogram Overview
Antibiotic Use Metric
Interpretation and Limitation of
DDD for Antibiotic Use Metric
IV to PO Toolkit 12.2014
CHS Toolkits
CHS ASP Program Development
and Expectations 02.2015
CHS ASP Strategies 09.10.2014
Dose Optimization
CHS Forms,
Templates,
Examples
Influenza Antiviral 2014-15 Flu
Season Update 01.2015
Zosyn Extended Infusion Dose
Autosub policy
Zosyn Extended Infusion Protocol
Basic overview of antibiogram, CLSI and Sentri7 antibiogram
function
Overview of defined daily dose (DDD), limitations and
instructions on data trending
Toolkit for IV to PO program: dose conversion table
table, training
slides, pocket card, progress notes for documentation, data
collection tool
Overview of ASP program development
CHS specific anti-infective strategies on preferred antibiotics
and its associated evidence
Update on 2014-15 flu season and availability of antiviral
treatment
Brief overview of Zosyn extended infusion use and dosing table
Brief description of Zosyn extended infusion rate
Ceftaroline alternatives example
Description of ceftaroline spectrum of activity, restricted use,
alternative agents for ceftaroline
Ertapenem alternatives example
Description
spectrum
off activity,
D
i ti off ertapenem
t
t
ti it restricted
t i t d use,
alternative agents for ertapenem
Tigecycline alternatives example
Description of tigecycline spectrum of activity, restricted use,
alternative agents for tigecycline
Sample usage criteria daptomycin
Sample usage criteria ertapenem
Sample usage criteria linezolid
Sample usage criteria tigecycline
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Description
Daptomycin recommended use, non-recommended use, other
considerations and dosing table
Ertapenem recommended use, non-recommended use, other
considerations and dosing table
Linezolid recommended use, non-recommended use, other
considerations and dosing table
Tigecycline recommended use, non-recommended use, other
considerations and dosing table
38
19
Antimicrobial Stewardship
CHS Pharmacy Education Series
Training
 Professional Development
 Tuition Reimbursement Benefits
 SIDP Certification
39
NHSN Reporting Requirements for HAI’s
 Sentri7 "Help & Training” link
 Q1 2015 Sentri7 Release Notes ((found in upper-right
pp
g section of
your Sentri7 dashboard)
40
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Antimicrobial Stewardship Program
Implementation Plan
 Baseline Facility Assessment  Antimicrobial metrics monitoring: DDD, antimicrobial expenditure PPMI survey results
 PPMI survey results  Governance: Advisory Group/Stakeholder Forum  Accountability structure  Antimicrobial stewardship task force  Clinical Resource  Electronic System Assistance  Collaboration with EHR C ll b ti
ith EHR
 Sentri7® use
 Antimicrobial Data Monitoring 41
Contact Info
[email protected]
615‐465‐2682
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Antimicrobial Stewardship
CHS Pharmacy Education Series
43
SIDP
The Society of Infectious Diseases Pharmacists
Antimicrobial Stewardship
AntimicrobialStewardship
JessicaRobinson,PharmD,BCPS
AssistantProfessorandInfectiousDiseasesClinicalPharmacy
Specialist
43
SIDP
44
AntimicrobialResistance
• Multi‐drugresistancedefined
– Nonsuceptibility toatleast1agentin3ormore
antimicrobialclasses
• >2millionpatientsacquireseriousinfectionswith
abacteriaresistanttooneormorecommonlyused
antibiotics
– ~23,000dieeachyear
23 000 di
h
– Manymorediefromconditionscomplicatedby
infections
http://www.cdc.gov/hicpac/mdro/mdro_2.html
http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
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SIDP
22
Antimicrobial Stewardship
CHS Pharmacy Education Series
45
AntimicrobialResistance
• Limitsavailabletherapy
• Delayinadministrationofappropriatetherapy
Delay in administration of appropriate therapy
– 3.5dvs.1d
• Resultsinpooreroutcomes
– Lowerresponserates
– Longertimetoachieveclinicalstability
– Higherinfection‐relatedmortality
• Highercost
– Estimateddirecthealthcarecostof$20billion
– Indirectcostin2008estimatedas$35billion
McGowan JE, et al. Am J Med 2006; 119: S29-36
http://www.idsociety.org/Topic_Antimicrobial_Resistance
SIDP
Hsu DI, J Antimicrob Chemother 2005; 55: 535:41
http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
46
CDC2013ThreatReport
Pathogen
#CasesAnnually
#Deaths Annually
ff
C.difficile
250,000
14,000
CRE
9,300
610
MDR Acinetobacter spp.
7,300
500
MDR P.aeruginosa
6,700
440`
ESBL
26,000
1,700
VRE
20,000
1,300
MRSA
80,000
11,000
Resistant S.pneumoniae
1,200,000
7,000
SIDP
http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
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Antimicrobial Stewardship
CHS Pharmacy Education Series
47
AntimicrobialApprovals
18
16
14
12
10
8
6
4
2
0
1983‐1987
1988‐1992
1993‐1997
1998‐2002
2003‐2007
2008‐2012
2013‐
present
SIDP
Adapted from: Boucher HW, et al. Clin Infect Dis 2013; 56(12): 1685-94
48
NewAntimicrobialAgents
SIDP
Boucher HW, et al. Clin Infect Dis 2013; 56(12): 1685-94
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Antimicrobial Stewardship
CHS Pharmacy Education Series
ExecutiveOrderfromPresident
Obama
49
• Plantocombatantimicrobial‐resistantbacteria
• Fivekeycomponents:
Fi e ke co o e ts
– Establishesataskforceforcombatingantibiotic‐resistant
bacteria
– Establishesthepresidentialadvisorycounciloncombating
antibiotic‐resistantbacteria
– Improvesantibioticstewardship
– Strengthensnationalsurveillanceeffortsforresistant
St
th
ti
l
ill
ff t f
i t t
bacteria
– Promotesthedevelopmentofnewandnext‐generation
antibioticsanddiagnostics
SIDP
50
ExecutiveOrder– ASP
• Byendof2016“shallreviewexisting
regulationsandproposenewregulationsor
l i
d
l i
otheractions,asappropriate,thatREQUIRE
HOSPITALSandotherinpatienthealthcare
deliveryfacilitiestoimplementrobustASPs
thatadheretobestpractices,suchasthose
identifiedbytheCDC”
SIDP
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Antimicrobial Stewardship
CHS Pharmacy Education Series
51
SIDP
http://www.cdc.gov/getsmart/healthcare/pdfs/checklist.pdf
52
WhatisAntimicrobial
Stewardship(ASP)?
• Arational,systematicapproachtotheuseof
antimicrobial agents in order to achieve optimal
antimicrobialagentsinordertoachieveoptimal
outcomes
• Goals:
– Optimizeclinicaloutcomes
• Ensureappropriateantimicrobialselection,dosing,routeof
administrationanddurationoftherapy
– Minimizeunintendedconsequencesofantimicrobial
use
• Includingdrugtoxicities,adverseeffectsandemergenceof
resistantpathogens
http://www.nebraskamed.com/careers/education-programs/asp
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
ProCE, Inc.
www.ProCE.com
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DesiredOutcomesofASP
• Better patient outcomes – the bottom line
– Decreased LOS,
OS, morbidity
y and mortality
y
• Improve antibiotic use throughout hospital
– Selection of agent, duration of therapy
• Stable or improved antibiogram data
• Stable or reduced rates of CDAD and HAI
• Economic benefits
– Stable or reduced antimicrobial expenses
– Reduced losses for HAI reimbursement issues
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Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
54
KeyMembersofanASP
Infection
Control
Nursing
Hospital
Hospital
Administration
Microbiology
Lab
Physician
Champion
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf
ProCE, Inc.
www.ProCE.com
Physician
Leaders
Pharmacist
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ProgramDevelopment
• Combinationofstrategiesrecommended
• MustdeterminewhatworksbestforYOUR
institution
• Educationpriortoimplementationiskey
– Gainsupportfromphysicianleaders
• Administrativesupportisrequired
Ad i i t ti
ti
i d
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf
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AntimicrobialStewardship
Strategies
• Corestrategies
– Prospectiveauditandfeedback
Prospective audit and feedback
– Antimicrobialrestriction/preauthorization
• Supplementalstrategies
–
–
–
–
–
Education
Guidelines/clinicalpathways
Doseoptimization
IVtoPOconversion
De‐escalationoftherapy/antibiotic“time‐out”
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SupplementalStrategies
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Education
• Mostfrequentlyemployedintervention
– KeycomponenttoanyASP
Key component to any ASP
• Oftenincludespassiveactivities
– Conferences/presentations
– Writtenguidelines/educationalmaterial
• MosteffectivewhencombinedwithotherASPstrategies
• Potentialdisadvantages/barriers:
– Rapidlossofknowledge
R id l
fk
l d
– Pooradherencetorecommendations
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
SIDP
Ohl CA, Beardsley JR, Whitehurst S. Available at: http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
ProCE, Inc.
www.ProCE.com
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Guidelines/ClinicalPathways
• Commonlyutilizedstrategiestoguideempirictherapy
– Mayincludeclinicaldecisionsupportsoftware
May include clinical decision support software
• Directsclinicianstomostappropriatetherapybasedon
hospitalspecificmicrobiologydata
• Increasescompliancewithevidencebasedguidelines
– Leadstoimprovedpatientoutcomes
• Providessignificantcostsavings
g
g
• Potentialdisadvantages/barriers:
– Underutilizationbyprescribers
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
Dean NC, et al. CHEST 2006; 130: 794-9
Jenkins TC, et al. Arch Intern Med 2011; 171(12):1072-9
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DoseOptimization
• Accountsfor:
– Individualpatientcharacteristics
Individual patient characteristics
– Causativeorganism/siteofinfection
– PK/PDparametersofthedrug
• Extendedinfusionβ‐lactams
• Pharmacokineticprotocols
• Ensuresoptimaltherapywithoutsacrificingpatient
outcomes
• Potentialdisadvantages/barriers:
– Timeintensive
– Nursingconcerns
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
ProCE, Inc.
www.ProCE.com
SIDP
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IVtoPOConversion
• Focusesonantimicrobialswithhighoralbioavailability
– Institutionpolicydictateseligiblepatients
Institution policy dictates eligible patients
• Simplecost‐savingsinitiative
• Otherbenefitsinclude:
– Decreasedlengthofstay
– Lowerincidenceofcatheter‐relatedbloodstreaminfections
– Reductioninworkload
• Potentialdisadvantage/barrier:
P t ti l di d
t /b i
– FalseperceptionthatIVtherapyjustifiescontinuedinpatientstay
tothird‐partypayers
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Goff DA, et al. Clin Infect Dis 2012; 55(4): 587-92
Ohl CA, Beardsley JR, Whitehurst S. Available at:
http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
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De‐escalationofTherapyand/or
Antibiotic“Time‐Out”
62
• De‐escalationbasedondiseasespecificand
patient specific findings
patientspecificfindings
– Prescribersmayberesistant,particularlyifculturesare
negative
– Fewstudiesavailabletosupportshort‐coursetherapy
• Antibiotic“time‐outs”encouragephysiciansto
review therapy at 48 hours
reviewtherapyat48hours
– Reliesonprescriber‐promptedde‐escalation
– Datatosupportthisapproachislacking
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf
ProCE, Inc.
www.ProCE.com
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CoreStrategies
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ProspectiveAuditandFeedback
• Prescribersorderantimicrobialsonformularywithoutrestriction
• Stewardshipteamreviewsantimicrobialtherapytodetermine
p
py
appropriatenessand/ortooptimizetherapyonanindividualpatient
basis
– Feedbackispatientspecific
• Canbeverbalorwritten
– Educationisakeycomponent
• Increasedappropriatenessoftherapy
– Faredbetterthanindicationbaseddosing
Fared better than indication based dosing
• Highacceptanceratesandimprovedcliniciansatisfaction
• Reducedantimicrobialconsumptionandsignificantcostsavings
– SignificantlyshorterdurationsoftherapyandDDD
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Bantar C, et al. Clin Infect Dis 2003; 37: 180-6
Camins BC, et al. Infect Control Hosp Epidemiol 2009; 30(10): 931-8
Amer MR, et al. Ann Saud Med 2013; 33(6): 547-54
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
ProCE, Inc.
www.ProCE.com
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ProspectiveAuditandFeedback
• Potentialbarriersinclude:
– Resourceintensive
– Requiresteammembertrainingandexperience
inanti‐infectivetherapy
• Multipleprogramsavailableforthosewithlimited
experience
– Difficultycommunicatingrecommendationsto
ff
providers
– Acceptanceofrecommendationisvoluntary
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
Ohl CA, Beardsley JR, Whitehurst S. Available at:
http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
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Restriction/Pre‐authorization
• Limitsavailableantimicrobialswithoutapprovalthroughvarious
means
– PreauthorizationcommonlyconductedbyIDphysicianand/orpharmacist
– Antimicrobialsmayalsoberestrictedtospecificindicationsand/or
services
• Betterclinicaloutcomesandincreasedappropriatenessoftherapy
• Producessignificantcostreduction
– $18PPDpre‐ vs $14.40PPDpost‐intervention
• Maystabilizeorimprovecurrentresistancepatterns
– White,etalfoundsignificantimprovementinantimicrobial
susceptibilities,particularlyinICUpatients
– Evidenceforreducingresistanceoftennotreproducible
Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
Gross R, et al. Clin Infect Dis 2001; 33: 289-95
Philmon C, et al. Infect Cont Hosp Epi 2006; 27(3): 239-44
White AC, et al. Clin Infect Dis 1997; 25: 230-9
ProCE, Inc.
www.ProCE.com
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Restriction/Pre‐authorization
• Potentialbarriersinclude:
– Lossofprescriberautonomy
– Timeintensive
– Potentialfordelayinadministering
antimicrobial
– Needfor“after‐hours”service
Drew RH, et al. Pharmacotherapy 2009; 29(5): 593-607
Ohl CA, Beardsley JR, Whitehurst S. Available at:
http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
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MetricsforASP
Indicator
Example
Patientoutcomes
In‐hospitalmortality
Lengthofstay(LOS)
Rate ofreadmission
Crudemortality forspecificinfections
Avg LOSofpatients;avg LOSinICU
Ratesofreadmission
Unintendedconsequences
Antibiotic‐resistantorganisms
C.difficile
%resistanceorratesofresistantpathogens
RateofC.difficile associateddisease
Antibioticutilizationandcosts
Expenditure
Utilization
Lengthoftreatment
Processmeasures
Appropriate therapy
Ratesofde‐escalation
Moneyspentpurchasing, dispensingoradministering
antibioticsperpatientadmissionorPPD
antibiotics
per patient admission or PPD
DDD,DOTorPPDperadmissionorpatientdays
Avg durationoftreatmentforspecificinfections
Proportionofappropriate regimensperguidelines
Proportionofde‐escalatedregimens
Adapted from: Dodds Ashley ES, Kaye KS, DePestel DD, et al. Clin Infect Dis 2014; 59 (S3): S112-21
Ohl CA, Beardsley JR, Whitehurst S. Available at:
http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
ProCE, Inc.
www.ProCE.com
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MetricsforASP
• Antimicrobialutilizationdataeasiestto
collect
ll
– Typicallyusedtodetermineprogram
effectivenessandjustifycostofASP’s
• Patientoutcomedatamoremeaningful
– ReflectstheprimarygoalofASP
Reflects the primary goal of ASP’ss
– Muchmoretime‐intensivetocollect
Dodds Ashley ES, Kaye KS, DePestel DD, et al. Clin Infect Dis 2014; 59 (S3): S112-21
Ohl CA, Beardsley JR, Whitehurst S. Available at:
http://www.jointcommission.org/topics/hai_antimicrobial_stewardship.aspx
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The Society of Infectious Diseases Pharmacists
The Role of Newly Approved Antimicrobial Therapy
Alan Gross, PharmD, BCPS
Infectious Diseases Pharmacist, University of Illinois Hospital
& Clinical Assistant Professor, Pharmacy Practice
University of Illinois at Chicago College of Pharmacy
70
ProCE, Inc.
www.ProCE.com
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Disclosure
• The speaker has no conflicts of interest to di l
disclose
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Objectives
• Review new antimicrobial agents
• Describe strategies to maximize cost‐
effectiveness of antimicrobial agents
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New FDA anti‐infective approvals 2014 ‐ current
Gram‐positive agents:
• Dalbavancin (Dalbavance®) – May 2014
(Orbactiv®)) – Aug. 2014
Aug. 2014
• Oritavancin (Orbactiv
• Tedizolid (Sivextro®) – June 2014
Gram‐negative agents:
• Ceftolozane/tazobactam (Zerbaxa®) – Dec. 2014
• Ceftazidime/avibactam (Avycaz®) – Feb. 2015
Antifungal:
• Isavuconazonium (Cresemba®) – Mar. 2015
Antiviral (influenza):
• Peramavir (Rapivab®) – Dec. 2014
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Background
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www.ProCE.com
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Spectrum of commonly used agents for skin/soft‐tissue infections (SSTI)
• Methicillin‐resistant Staphylococcus aureus (MRSA):
– Vancomycin > linezolid > SMX‐TMP > doxycycline > clindamycin
• Methicillin‐susceptible Staphylococcus aureus (MSSA):
– All agents listed for MRSA – AND oxacillin/nafcillin/dicloxacillin, cephalexin, cefazolin
• Streptococcus spp. (Group A Streptococcus)
– Penicillin, oxacillin/nafcillin, cephalexin, cefazolin, vancomycin, clindamycin
y
Daptomycin, linezolid/tedizolid, ceftaroline, tigecycline,
oritavancin, dalbavancin all typically have MRSA and
Are there other agents with MRSA activity?
Streptococcus activity and carry FDA-indications for SSTI.
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But are typically not necessary.
76
Fun with nomenclature:
SSTIs to ABSSSIs
• Acute bacterial skin and skin structure infections
– Studies
Studies utilizing new FDA criteria
utilizing new FDA criteria1 for diagnosis and for diagnosis and
outcome measurement
• ABSSSI: “a bacterial infection of the skin with a lesion size area of at least 75 cm2 (lesion size measured by the area of redness, edema, or induration).” 1
• Aim of new criteria is to ensure patients are sick enough in noninferiority studies to appreciate a
enough in noninferiority studies to appreciate a treatment effect
– Minor cutaneous abscesses that have been drained typically resolve without antibiotic therapy
1. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
ProCE, Inc.
www.ProCE.com
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ABSSSI endpoints1
• Primary efficacy endpoint for ABSSSI:
– Percent decrease in lesion size at 48 ‐ 72 hours
– Generally 20% reduction is considered response
• Secondary endpoint:
– Resolution of ABSSSI evaluated at 7 to 14 days after completion of therapy
after completion of therapy
• Noninferiority margin of 10% is reasonable
1. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
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New Gram‐positive agents
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ProCE, Inc.
www.ProCE.com
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Dalbavancin
• Lipoglycopeptide analogue of vancomycin with G
Gram‐positive activity including S. aureus, iti
ti it i l di S
Streptococcus spp., Enterococcus (not harboring vanA)
• FDA indication: ABSSSI
• T1/2
: 2 weeks
/ : 2 weeks
• Dosing: 1g IV x1dose followed by 500mg on day 8
• Dose adjust if creatinine clearance <30 ml/min
Dalbavancin Package Insert. Durata. Chicago,IL. 5/2014.
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DISCOVER 1 & 2
• Double‐blind, double‐dummy, international randomized controlled noninferiority
d i d
t ll d
i f i it studies t di
1
with identical designs
– Dalbavacin vs vancomcyin+linezolid for ABSSSIs
• Vancomycin dosed per individual institution or 1g q12h, after 3 days option to switch to linezolid
• Primary endpoint per FDA guidance:2
– Early clinical response based on cessation of spread of erythema and afebrile
1. Boucher HW, et al. NEJM. 2014
2. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
ProCE, Inc.
www.ProCE.com
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DISCOVER 1 & 2
• Inclusion criteria per FDA industry guidance2
• Cellulitis, abscess, or major wound infection C ll liti b
j
d i f ti
2
≥75 cm with at least one systemic sign of infection (>38C or WBC>12k) and at least two local signs of infection:
– Purulence
– Local warmth
L l
h
– Tenderness on palpation
– Swelling/induration
1. Boucher HW, et al. NEJM. 2014
2. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
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DISCOVER 1 & 2 pooled results
• 1312 patients in pooled analysis
85% of patients were febrile at enrollment and median
• 85% of patients were febrile at enrollment and median lesion size was ~340 cm2
• Primary endpoint
– Early clinical response in 79.7% vs 79.8% in patients receiving dalbavancin vs vancomycin/linezolid, respectively (95% CI ‐4.5% to 4.2%)
– Outcomes similar when analyzed by patient subgroups including infection type infection severity
including infection type, infection severity
– No difference in outcomes at later evaluation time points
• No difference in treatment‐limiting adverse events (~2% in each treatment group) Boucher HW, et al. NEJM. 2014
ProCE, Inc.
www.ProCE.com
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Oritavancin
• Lipoglycopeptide analogue of teicoplanin with Gram‐positive activity including S aureus
Gram‐positive activity including S. aureus, Streptococcus spp. Enterococcus (↑MIC for VRE)
• FDA indication: ABSSSI
• T1/2: 10 days
• Dosing: 1200 mg IV x 1 dose administered over 3 hrs
• Dose adjustments not required in hepatic/renal dysfunction
Oritavancin Package Insert. The Medicines Co. Parsippany, NJ. 8/2014.
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SOLO‐1 & 2
• Single‐dose Oritavancin in the treatment of acute bacterial skin infections
bacterial skin infections
• Double‐blind international randomized controlled noninferiority studies with identical design1
– Oritavancin vs vancomcyin x7‐10d for ABSSSIs
• Vancomycin dosed 1g or 15 mg/kg q12h
• Inclusion
Inclusion criteria per FDA guidance
criteria per FDA guidance3
• Primary endpoint per FDA guidance:3
– Early clinical response (48‐72h) based on cessation of spread or reduction of erythema and afebrile
1. Corey RG, et al. NEJM. 2014.
2. Corey RG, et al. CID. 2015
3. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
ProCE, Inc.
www.ProCE.com
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SOLO‐1 results
• 954 patients included in modified intention‐to‐treat analysis.
• 15% of patients were febrile at enrollment and median lesion size was ~240
size was 240 cm
cm2
• Primary endpoint
– Early clinical response in 79.7% vs 79.8% in patients receiving oritavancin vs vancomycin, respectively (95% CI: ‐1.6% to 8.4%)
– Outcomes similar when analyzed by patient subgroups including obesity, diabetes, age, MRSA infection, infection type
• No difference in outcomes at later evaluation time points
• Most adverse effects mild. No difference in treatment‐
Most adverse effects mild No difference in treatment
limiting adverse events (~2.3% oritavancin, 2.7% vancomycin)
• SOLO‐2 findings are consistent with SOLO‐1
1. Corey RG, et al. NEJM. 2014.
2. Corey RG, et al. CID. 2015.
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Tedizolid
• Oxazolidinone with Gram‐positive activity i l di S
including S. aureus, Streptococcus spp., St t
Enterococcus spp.
• FDA indication: ABSSSI
• T1/2: 12h
• Dosing: 200 mg IV/PO once daily
Dosing 200 mg IV/PO once daily
• Dose adjustment not required for renal/hepatic dysfunction
Tedizolid Package Insert. Cubist. Lexington, MA. 6/2014.
ProCE, Inc.
www.ProCE.com
SIDP
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ESTABLISH‐1 & 2
• Double‐blind, double‐dummy international randomized controlled noninferiority studies d i d
t ll d
i f i it t di
with similar design1,2
– Tedizolid x 6 days vs linezolid x 10 days for ABSSSIs
• ESTABLISH‐2 required patients receive at least the first dose via IV route with subsequent optional oral step down
• Inclusion criteria per FDA guidance3
1. Prokocimer P, et al. ESTABLISH-1. JAMA 2013.
2. Moran GJ, et al. ESTABLISH-2. Lancet Infect Dis. 2014.
3. Guidance for industry: ABSSSIs: developing drugs for treatment. FDA. 2013.
ESTABLISH‐1 & 2 results
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1. Prokocimer P, et al. ESTABLISH-1. JAMA 2013.
2. Moran GJ, et al. ESTABLISH-2. Lancet Infect Dis. 2014.
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3. Tedizolid Package Insert. Cubist. Lexington, MA. 6/2014.
ProCE, Inc.
www.ProCE.com
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Adverse effects, pooled phase III data
Tedizolid 200 mg once daily Linezolid 600 mg q12h
x 6 days
x 10 days
(n=618)
(n=617)
Anemia
((Hemoglobin <10.1, males; g
,
;
<9 g/dL, females)
3.1%
3.7%
Thrombocytopenia (Platelets <112x103/mm3)
2.3%
4.9%
Neutrophils (<0.8x103/mm3)
0.5%
0.6%
89
• Myelosuppression similar between groups
– Myelosuppression increases with increased dose and duration • Package insert notes this was seen with tedizolid in phase 1 studies beyond 6 days of exposure
– No bleeding events
• Peripheral neuropathy in 1.2% and 0.6% of tedizolid and linezolid groups, respectively
• Patients receiving MAOIs or serotonergic agents excluded from phase III tedizolid studies
Tedizolid Package Insert. Cubist. Lexington, MA. 2014.
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FDA
indication
Dosing
AWP* for course
Notes
Dalbavancin
ABSSSI
1000 mg and 500 mg $5364
IV on days 1 and 7,
respectively
Oritavancin
ABSSSI
1200 mg IV x 1 dose administered over 3
hrs
$3480
Falsely elevates aPTT/INR, heparin therapy requiring monitoring contraindicated for 48h post orita dose
Tedizolid
ABSSSI
200 mg IV/PO once daily
6 day course:
IV: $1692
IV: $1692
PO: $2124
No clear distinguishing clinical characteristic
relative to linezolid besides
relative to linezolid besides once daily dosing
*AWP, average wholesale retail price as of 3/9/15
Vancomycin 1g q12h 7 day course of therapy, AWP: $86
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How can we promote optimal p
p
outcomes and cost‐effectiveness for SSTIs?
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Diffuse nonpurulent skin infection (cellulitis/erysipelas)
• Typically caused by Streptococcus spp. (especially Group A Streptococcus)
Group A Streptococcus)
• Mild: oral PCN, dicloxacillin, cephalosporin, clindamycin
• Moderate (systemic symptoms): IV PCN, cefazolin, ceftriaxone, clindamycin
cefazolin, ceftriaxone, clindamycin
• Severe: vancomycin IV + piperacillin/tazobactam
– Consider surgery and ID consult
Stevens DL, et al. Clinical Infectious Diseases, 2014.
ProCE, Inc.
www.ProCE.com
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Diffuse nonpurulent skin infection (cellulitis/erysipelas)
• “Outpatient therapy is recommended for patients who do not have SIRS, altered mental status, or hemodynamic instability (mild nonpurulent) (strong, moderate).” • “Hospitalization is recommended if there is concern for a deeper or necrotizing infection, for patients with poor adherence to therapy, for infection in a severely immunocompromised infection
in a severely immunocompromised
patient, or if outpatient treatment is failing (moderate or severe nonpurulent) (strong, moderate).”
Stevens DL, et al. Clinical Infectious Diseases, 2014.
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Cellulitis associated with abscesses (purulent/culturable)
• Typically associated with S. aureus
• Incision and drainage is often curative and antibiotics may be g
y
unnecessary
– Lance site and express pus, culture
• Consider antibiotics in moderate/severe disease:
–
–
–
–
Extensive surrounding cellulitis
Rapidly progressive Fever or other systemic symptoms
Underlying immune deficiencies/advanced age
Underlying immune deficiencies/advanced age
• Moderate, oral TMP/SMX or doxycycline
• Severe, IV agent active for MRSA including (i.e. vancomycin)
Stevens DL, et al. Clinical Infectious Diseases, 2014.
ProCE, Inc.
www.ProCE.com
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Severe skin infections
• First consider comparative efficacy, then toxicity, then spectrum and cost
then spectrum and cost
Efficacy:
• Is oritavancin, dalbavancin, daptomycin, ceftaroline, etc. more effective than vancomycin?
– No adequate data supporting superiority of another agent relative to vancomycin for severe skin/soft tissue
agent relative to vancomycin for severe skin/soft tissue infections.
– What about elevated vancomycin MIC in S. aureus infections?
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S. aureus
96
• What if S. aureus vancomycin MIC is high (1.5 or 2 mcg/ml) but susceptible (MIC ≤2)?
– IDSA
IDSA MRSA guidelines state that for susceptible MRSA guidelines state that for susceptible
isolates: “patient’s clinical response should determine the continued use of vancomycin, independent of the MIC (A‐III)”1
• Vancomycin is first‐line, if not improving consider source control1,2
– It is a controversial and complex issue but current data p
are not adequate to support the routine use of an alternative agent based on MIC as long as susceptible1‐3
1. Liu C, et al. Clin Infect Dis. 2011 Feb 1;52(3):e18-55.
2. van Hal SJ, Fowler VG. Clin Infect Dis. 2013 Jun;56(12):1779-88.
3. Kalil AC, et al. JAMA. Published online Oct. 9, 2014.
ProCE, Inc.
www.ProCE.com
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Kalil AC, et al. Oct. 2014
• Largest meta‐analysis to date evaluating vancomycin MIC in S aureus bacteremia and
vancomycin MIC in S. aureus bacteremia and mortality
• 8291 episodes of S. aureus bacteremia:
– 26.8% and 25.8% mortality with high and low MICs, respectively; 1.6% RD (‐2.3% to 5.6%) P = 0.43
• Also no difference in mortality when only including high quality data or MRSA isolates
Kalil AC, et al. JAMA. Published online Oct. 9, 2014.
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Severe skin infections
• First consider comparative efficacy, then toxicity, then spectrum and cost
Efficacy:
• Is oritavancin, dalbavancin, daptomycin, ceftaroline, etc. more effective than vancomycin?
– No adequate data supporting superiority of another agent relative to vancomycin for severe skin/soft tissue infections.
Toxicity?
Other patient‐specific
Other patient
specific factors?
factors?
‐Most patients requiring IV therapy may need to be admitted
Suggest, at a minimum, formulary restriction criteria for the new Gram‐positive agents and education of prescribers
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www.ProCE.com
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Antimicrobial Stewardship
CHS Pharmacy Education Series
101
Gram‐negative agents
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CDC. Antibiotic resistance threats in the102
United States, 2013.
ProCE, Inc.
www.ProCE.com
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Antimicrobial Stewardship
CHS Pharmacy Education Series
103
Beta‐lactamases are a common mechanism of resistance in Gram‐negative bacteria • Class A (serine)
– SHV, TEM, CTX‐M, KPC
• Class B (metallo)
– NDM, IMP, VIM
• Class C (serine)
– AmpC
A C
• Class D (serine)
– OXA
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New FDA anti‐infective approvals 2014 ‐ current
Gram‐negative agents:
Gram
negative agents:
• Ceftolozane/tazobactam (Zerbaxa®) – Dec. 2014
• Ceftazidime/avibactam (Avycaz®) – Feb. 2015
• Both agents given priority review and approved based on phase II and preliminary phase III data given important unmet medical need (serious/life‐threatening infections).
SIDP
ProCE, Inc.
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52
Antimicrobial Stewardship
CHS Pharmacy Education Series
105
Ceftolozane/tazobactam
• A novel cephalosporin combined with beta‐
lactamase inhibitor – Ceftolozane – Pseudomonas and enteric activity, active against AmpC producers
– Tazobactam inhibits some class A and C beta‐
lactamases
– Does not inhibit KPC or metallo
Does not inhibit KPC or metallo beta lactamases
beta lactamases
– Poor S. aureus activity (MIC50 =32; MIC90 =64 mcg/ml)
Solomkin J, et al. CID 2015 electronic advance access.
Ceftolozane/tazobactam Package Insert. Cubist. Lexington, MA. 12/2014.
Zhanel GG, et al. Drugs. 2014.
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Ceftolozane/tazobactam
• FDA indication: cUTI, cIAI
• T1/2: 3h/1h
: 3h/1h
• Dosing: 1.5g IV q8h, 1h infusion
– Dose adjust if CrCl <50 ml/min
cUTI, complicated urinary tract infection; cIAI, complicated intra-abdominal
infection
Solomkin J, et al. CID 2015 electronic advance access.
Ceftolozane/tazobactam Package Insert. Cubist. Lexington, MA. 12/2014.
Zhanel GG, et al. Drugs. 2014.
ProCE, Inc.
www.ProCE.com
SIDP
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Ceftolozane/tazobactam Minimum Inhibitory Concentrations (mg/L) Pathogen Enterobacteriaceae S
≤2/4 I
4/4
R
≥8/4 Pseudomonas aeruginosa ≤4/4 8/4
≥16/4 107
Ceftolozane/tazobacta
m Package Insert.
Cubist. Lexington,
MA. 12/2014.
Zhanel GG, et al.
Drugs. 2014.
S, susceptible; I, intermediate; R, resistant
Pseudomonas aeruginosa
Imi/meropenem-non-susceptible
Imi/meropenem
non susceptible Pseudomonas
Tobramycin-resistant Pseudomonas
Ceftaz and meropenem-non-susceptible Pseudo
Cefepime-non-susceptible Pseudomonas
KPC-producing Klebsiella
MIC50
0.5
1
2
4
4
>16
MIC90
2
8
64
≥32
>16
MIC50 MIC90, minimum concentration (mg/L) to inhibit growth of 50 % or 90% of isolates SIDP
108
Ceftazidime/avibactam
• Ceftazidime combined with a novel beta‐
l t
lactamase inhibitor with broad beta‐lactamase i hibit
ith b d b t l t
activity
– Avibactam inhibits some Class A, C, and D beta‐
lactamases, not class B (metallo)
• Active against some ESBLs
– 1‐5 molecules of avibactam required to inhibit one beta lactamase molecule (>50 for tazobactam and clavulanic acid) SIDP
ProCE, Inc.
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54
Antimicrobial Stewardship
CHS Pharmacy Education Series
109
Ceftazidime/avibactam
• FDA indication: cUTI, cIAI
• T1/2: 3h/2.5h
• Dosing: 2.5g IV q8h, 2h infusion
– Dose adjust if CrCl <50 ml/min
Ceftazidime/avibactam Package Insert. Forest Pharmaceuticals. Cincinnati, OH. 2/2015.
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110
FDA Breakpoints
Ceftazidime/avibactam
Pathogen
Pathogen Ceftazidime/avibactam Minimum Inhibitory Concentrations (mg/L) Enterobacteriaceae S
≤8/4 R
≥16/4 Pseudomonas aeruginosa ≤8/4 ≥16/4 S, susceptible; R, resistant
Ceftazidime/avibactam Package Insert. Forest Pharmaceuticals. Cincinnati, OH. 2/2015.
ProCE, Inc.
www.ProCE.com
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Antimicrobial Stewardship
CHS Pharmacy Education Series
111
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111
Anti-infective drugs advisory committee. FDA CDER. 12/5/14.
112
Top‐level results of Phase III cIAI study
• “In the subgroup of patients with baseline CrCL of > 30 mL/min and ≤ 50 mL/min, lower of > 30 mL/min and ≤ 50 mL/min lower
clinical cure rates (45% vs 74%) and numerically higher mortality was seen in the CAZ‐AVI arm compared to meropenem ”
• Likely due to inappropriate low exposure with renal dose adjustment used in this study
renal dose adjustment used in this study.
– Label now recommends a 50% increased dose relative to initial recommendations for patients with compromised renal function
SIDP
Anti-infective drugs advisory committee. FDA CDER. 12/5/14.
ProCE, Inc.
www.ProCE.com
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Antimicrobial Stewardship
CHS Pharmacy Education Series
New Gram‐negative agent summary
FDA
indications
Ceftolozane/
tazobactam
cUTI
cIAI
Dosing
AWP* for course
Ceftolozane 1g/ 7 day tazobactam 0.5g course:
IV q8h,
$2092
1h infusion
1h infusion
113
Notes
May be active against MDR Gram‐negatives including Pseudomonas
Must be combined with metronidazole if requiring Bacteroides coverage (cIAI)
Ceftazidime/
Avibactam
cUTI
cIAI
Ceftazidime 2g/
avibactam 0.5g IV q8h, 2h infusion
7 day course:
TBD
May be active against MDR Gram‐negatives including Pseudomonas
Novel activity against KPC
Novel activity against KPC‐
producing bacteria
*AWP, average wholesale retail price as of 3/9/15
Must be combined with metronidazole if requiring Bacteroides coverage (cIAI)
cUTI, complicated urinary tract infection; cIAI, complicated intra-abdominal infection;
KPC, Klebsiella pneumoniae carbapenemase; MDR multidrug-resistant
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Role of new Gram‐negative agents
• Ceftazidime/avibactam:
– “As only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options. ”
Ceftazidime/avibactam Package Insert. Forest Pharmaceuticals. Cincinnati, OH. 2/2015.
ProCE, Inc.
www.ProCE.com
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Antimicrobial Stewardship
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Summary
• Many new antibiotics!! – Lots
Lots of options for Gram‐positive infections
of options for Gram positive infections
– Still need more options for Gram‐negatives; however we now have a beta lactam with in vitro activity for KPC (ceftazidime/avibactam)!!
• Antimicrobial stewardship by pharmacists remains paramount to optimizing patient outcomes, continued effectiveness of available therapy
– Formulary management, education
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ProCE, Inc.
www.ProCE.com
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Antimicrobial Stewardship
CHS Pharmacy Education Series
Update on Current U
Update on Current Pharmacy d t
C
t Pharmacy Ph
Initiatives and Strategies
Robert Fink, Pharm.D., M.B.A., FASHP, FACHE, BCNSP, BCPS
Chief Pharmacy Executive
Community Health Systems
119
120
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