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Purchasing Power for HealthcarePurchasing Power for Healthcare
Institutional Approaches to Antimicrobial Stewardship
John Theobald, Pharm D
Director of Clinical Pharmacy Services
HealthTrust Purchasing Group
Gita Wasan Patel, Pharm D
Clinical Pharmacy Coordinator
Medical Center of Plano
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Objectives
• Describe the rationale for the development of antimicrobial stewardship programs
• Provide core strategies to assist in the development and implementation of antimicrobial stewardship programs
• Explore the ways that antimicrobial stewardship interventions can be tailored to improve outcomes
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Rationale for Antimicrobial Stewardship Programs
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High Rates of NosocomialInfections in the United States
Variable
No. of admissions (millions)
No. of patient days (millions)
Average length of stay (days)
No. of inpatient surgical procedures (millions)
No. of nosocomial infections (millions)
Incidence of nosocomial infections (no. per 1000 patient-days)
1975
37.7
299.0
7.9
18.3
2.1
7.2
1995
35.9
190.0
5.3
13.3
1.9
9.8
Year
Nosocomial Infections in the United States
Adapted with permission from Burke JP. N Engl J Med. 2003;348:651-656.
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Changing Resistance/Decreased Susceptibilities Over Time
Ceftazidime- and Imipenem-Resistant Acinetobacter (NNIS 1986-2003)
1986 1988 1990 1992 1994 1996 1998 2000
Year
20020
1020304050607080
Imipenem
Ceftazidime
% o
f Res
ista
nt Is
olat
es
2004
Resistance to Third-Generation Cephalosporins AmongKlebsiella Pneumoniae and Escherichia Coli (NNIS 1986-2003)
1986 1988 1990 1992 1994 1996 1998 2000
Year
20020
5
10
15
20
25
E Coli
K Pneumoniae
% o
f Res
ista
nt Is
olat
es
2004
NNIS = National Nosocomial Infections Surveillance System.Results of Cochran-Armitage 2 tests for trend were significant for both organisms and for both drugs (P<.001).
Adapted with permission from Gaynes R et al. Clin Infect Dis. 2005;41:848-854.
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Increasing Resistance: Gram-Positive Pathogens Also a Problem
Note: Data refer to infections in intensive care unit (ICU) patients only.
Sources: VRE and MRSA data, 1998-2000, 2002-2003 (CDC 1999; CDC 2000; CDC 2001; CDC 2003; CDC 2004); data for 2001 are for the average of 2000 and 2002 data. MRSA data from 1987-1997 are estimated from Lawy 1998. VRE data for 1989 and 1993 are from CDC 1993. VRE data for 1990-1992 and 1994-1997 are interpolated based on geometric mean.Available at: http://www.extendingthecure.org/downloads/ETC_FULL.pdf. Accessed April 30, 2007.
70
60
50
40
30
20
10
01987 1989 1991 1993 1995 1997 1999 2001 2003
Proportion of Methicillin-Resistant Staphylococcus Aureus (MRSA) and Vancomycin-Resistant Enterococcal (VRE) Infections Is
Increasing (1987-2003)
MRSA
VRE
% o
f R
esis
tan
t Is
ola
tes
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1. Stein GE. Pharmacotherapy. 2005;25:44S-54S.2. South M et al. Med J Aust. 2003;178:207-209.3. McGowan JE Jr. Clin Infect Dis. 2004;38:939-942.4. Levy SB. J Antimicrob Chemother. 2002;49:25-30.
Factors Encouraging the Development of Antimicrobial-Resistant Pathogens
• High severity of illness in patients once hospitalized1
• Inappropriate antibiotic use2
– Prolonged use or inadequate antimicrobial exposure
• Institutional factors3
• Agricultural use of antimicrobials4
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Increased Antibiotic Use Drives Resistance
Increasing fluoroquinolone resistance in Gram-negative bacilli correlates with increased fluoroquinolone use in patients from 43 states (numbers of isolates from 1994-2000=35,790). The 1990 to 1993 data points represent composite susceptibility and quinolone use for those 4 years.
Adapted with permission from Neuhauser MM et al. JAMA. 2003;289:885-888.
35
0
5
10
15
20
25
30
250
0
200
150
100
50% o
f S
trai
ns
Res
ista
nt
to C
ipro
flo
xaci
n Qu
ino
lon
e Use
(kg x 10
3)
1990-1993 1994 1995 1996 1997 1998 1999 2000
PseudomonasGram-NegativeFluoroquinolone use
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Causal Associations Between Antimicrobial Use and Emergence of Antimicrobial Resistance
• Changes in antimicrobial use are paralleled by changes in prevalence of resistance
• Antimicrobial resistance is more prevalent in health care–associated infections compared with community-acquired infections
• Patients with health care–associated infections caused by resistant strains are more likely than control patients to have prior antibiotic exposure
• Areas within hospitals with the highest rates of antimicrobial resistance also have the highest rates of antimicrobial use
• Increased length of exposure to antimicrobials increases the likelihood of colonization with resistant organisms
Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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Mortality Rates Correlate With Presence of Multidrug-Resistant Organisms
• Association between development of antimicrobial resistance in Staphylococcus aureus, enterococci, and Gram-negative bacilli and mortality1
• Pseudomonas aeruginosa is increasingly resistant to fluoroquinolones, with a number of consequences, including infection-related mortality2
• Enterococcal infections have been associated with mortality ratesexceeding 30%3
• A meta-analysis of published studies found that patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia had an increased risk of mortality compared with patients who had methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia (OR = 1.93; P<.001)4
1. Cosgrove SE. Clin Infect Dis. 2006;42(suppl 2):S82-S89.2. McGowan JE Jr. Am J Infect Control. 2006;34:S29-S37.3. Lautenbach E et al. Clin Infect Dis. 2003;36:440-446.4. Cosgrove SE et al. Clin Infect Dis. 2003;36:53-59.
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FDA = Food and Drug Administration.
Available at: http://www.extendingthecure.org/downloads/ETC_FULL.pdf. Accessed April 30, 2007.Source: 1983-2002 (Spellberg et al. 2004), 2003-2005 (Bosso 2005).
Fewer Antibiotics to Address Increased Resistance
16
14
1086420
1983-1987
12
New
An
tim
icro
bia
ls A
pp
rove
d
1988-1992 1993-1997 1998-2002 2003-2005
Antibacterial Agents Approved by FDA, 1983-2005
Fewer New Antibiotics Are Being Brought to Market as More Companies Leave the Anti-Infectives Business
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Economic Impact of Increased Resistance
• During 2004, it was estimated that at least $20 billion was billed nationally to Medicare for hospital-acquired infections1
• Many were resistant to one or more classes of antibiotics
• Increased cost can come from periodic switches to newer, more expensive antibiotics1
• Costs have increased with increased prophylactic use of antibiotics, and their use in immunocompromised patients1
• Direct excess medical cost due to resistant infections comprises only a small portion of the potential cost to society2
1. Available at: http://www.extendingthecure.org/downloads/ETC_FULL.pdf. Accessed April 30, 2007.2. Scott D II et al. In: Owen RC Jr et al, eds. Antibiotic Optimization: Concepts and Strategies in Clinical Practice. Marcel Dekker Publishers. 2005.
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Other Economic Impacts of Increased Resistance
Medicare payments adjusted for hospital-acquired conditions, including infections
Medicare will pay a lower rate for hospital-acquired infections
Adapted from US Department of Health and Human Services. 42 CFR Parts 411, 412, 413, and 489 Medicare Program; Proposed Changes to the Hospital Inpatient Prospective Payment Systems and Fiscal Year 2008 Rates; Proposed Rule. Effective October 1, 2007. Available at: http://www.asm.org/ASM/files/LeftMarginHeaderList/DOWNLOADFILENAME/000000002404/CMSProposedRuleHAQ.pdf. Accessed June 28, 2007.
Proposed Changes Effective in 2007
Proposed Changes Open for Comment in 2008
1. Catheter-associated urinary tract infections
2. Pressure ulcers (decubitus ulcers)
3. Serious preventable event—object leftin surgery
4. Serious preventable event—air embolism
5. Serious preventable event—blood incompatibility
6. Staphylococcus aureus septicernia
7. Ventilator-associated pneumonia (VAP)/pneumonia
8. Vascular catheter–associated infections
9. Clostridium difficile–associated disease (CDAD)
10. Methicillin-resistant staphylococcusaureus (MRSA)
11. Surgical site infections
12. Serious preventable event—wrong surgery
13. Falls
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Antimicrobial Stewardship Programs
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Antimicrobial Stewardship
The optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent development of resistance.
Owens RC, Ambrose PG. Diagn Microbiol Infect Dis. 2007;57(suppl 3):S77-S83.
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Antimicrobial Stewardship: Overview
• Updated guidelines for developing programs to enhance antimicrobial stewardship published in 2007
• IDSA/SHEA*consensus guidelines endorsed by• American Academy of Pediatrics• American Society of Health-System Pharmacists• Infectious Diseases Society for Obstetrics and Gynecology• Pediatric Infectious Diseases Society• Society for Hospital Medicine• Society of Infectious Diseases Pharmacists
• Primary goal• Optimize clinical outcomes while minimizing unintended consequences
of antibiotic use– Toxicity– Selection of pathogenic bacteria (eg, Clostridium difficile)– Emerging resistance
• Secondary goal• Reduce health care cost without compromising quality of care
*Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA).
Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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Antimicrobial Stewardship Teams
ASP = Antimicrobial Stewardship Program, ID = infectious disease, P&T = Pharmacy and Therapeutics.Dellit TH et al. Clin Infect Dis. 2007;44:159-177 and Fishman N. Am J Med. 2006;119:S53-S61.
Multidisciplinary Team Approach to Optimizing Clinical Outcomes
HospitalHospitalEpidemiologistEpidemiologist
HospitalHospitalEpidemiologistEpidemiologist
InfectionInfectionControlControl
InfectionInfectionControlControl
MedicalMedicalInformationInformation
SystemsSystems
MedicalMedicalInformationInformation
SystemsSystems
MicrobiologyMicrobiologyLaboratoryLaboratory
MicrobiologyMicrobiologyLaboratoryLaboratory
InfectiousInfectiousDiseases Diseases DivisionDivision
InfectiousInfectiousDiseases Diseases DivisionDivision
Director,Director,OutcomesOutcomesResearchResearch
Director,Director,OutcomesOutcomesResearchResearch
Chairman,Chairman,P&TP&T
CommitteeCommittee
Chairman,Chairman,P&TP&T
CommitteeCommittee
Partners in Partners in OptimizingOptimizing
Antimicrobial Use SuchAntimicrobial Use Suchas Pulmonologistsas Pulmonologists
and Surgeonsand Surgeons
Partners in Partners in OptimizingOptimizing
Antimicrobial Use SuchAntimicrobial Use Suchas Pulmonologistsas Pulmonologists
and Surgeonsand Surgeons
HospitalHospitalAdministratorAdministrator
HospitalHospitalAdministratorAdministrator
ASP DirectorsASP Directors•• ID PharmD ID PharmD•• ID Physician ID Physician
ClinicalClinicalPharmacyPharmacySpecialistsSpecialists
ClinicalClinicalPharmacyPharmacySpecialistsSpecialists
DecentralizedDecentralizedPharmacyPharmacySpecialistSpecialist
DecentralizedDecentralizedPharmacyPharmacySpecialistSpecialist
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Core Strategies For Antimicrobial Stewardship
• Prospective audit with intervention and feedback
• Formulary restriction/preauthorization
Dellit TH et al. Clin Infect Dis. 2007;44:159-177 and Fishman N. Am J Med. 2006;119:S53-S61.
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Core Strategy 1: Prospective Audit With Intervention and Feedback
• Involves concurrent review of patients receiving antimicrobials
• Inappropriate orders initiate interaction between antimicrobial team members and the prescriber1
• Goal is to enhance antimicrobial stewardship (optimize selection, dose, duration, route)
• Advantages
• Avoids loss of autonomy for prescribers1
• Creates incentives for physicians to improve performance2
• Disadvantages
• Compliance is voluntary1
• Less effective unless it distinguishes between appropriate and inappropriate prescribing2
1. MacDougall C, Polk RE. Clin Microbiol Rev. 2005;18:638-656.2. Available at: http://www.extendingthecure.org/downloads/ETC_FULL.pdf. Accessed April 30, 2007.
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Jan 0
3
July 0
2
Jan 0
2
July 0
1
Jan 0
1
July 0
0
Jan 0
0
Sept 9
9
Vertical dashed line = program begun.
Adapted with permission from Fowler S et al. J Antimicrob Chemother. 2007;59:990-995.
Prospective Audit With Intervention and Feedback: Example 1
02468
101214
Num
ber o
f CD
I Cas
espe
r Mon
th
02468
101214
7-D
ay C
epha
losp
orin
Cou
rses
per 1
00 A
dmis
sion
s
Decrease in Cephalosporin Use
Lower Rates of Clostridium Difficile Infection
05
101520
30
4045
0102030405060
7-D
ay C
ours
espe
r 100
Adm
issi
ons
Decrease in Amoxicillin/Clavulanate Use
Increased Benzyl Penicillin Use
25
35
7-D
ay C
ours
espe
r 100
Adm
issi
ons
Jan 0
3
July 0
2
Jan 0
2
July 0
1
Jan 0
1
July 0
0
Jan 0
0
Sept 9
9
Jan 0
3
July 0
2
Jan 0
2
July 0
1
Jan 0
1
July 0
0
Jan 0
0
Sept 9
9
Jan 0
3
July 0
2
Jan 0
2
July 0
1
Jan 0
1
July 0
0
Jan 0
0
Sept 9
9
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Prospective Audit With Intervention and Feedback: Example 2
*Parental antibiotic use, cost per 1000 patient-days, and Medicare Case Mix Index trends following implementation of an antibiotic management program.
Adapted with permission from Carling P et al. Infect Control Hosp Epidemiol. 2003;24:699-706.
Parenteral Antibiotic Use, Cost Decreased*
Rates of Resistant Enterobacteriaceae Infections Decreased
0
20
10
-10
-20
-30
-401991 1992 1993 1994 1995 1996 1997 1998
Cost
Use
Illness Severity
% o
f P
rein
terv
enti
on
Ob
serv
atio
ns
1989 1990 1991 1992 1993 1995 1998
4
6
5
3
2
11994 1996 1997
Cas
es p
er 1
000
Pat
ien
t D
ays
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Core Strategy 2: Formulary Restriction/Preauthorization
• Effective method to control antibiotic use and cost; conflicting results on decreasing antimicrobial resistance1
• Advantages
• Provides the most direct control over antimicrobial use2
• Disadvantages
• Prescribers may feel loss of autonomy2
• Team members must have contingency plans foroff-hour approvals1
• May discourage appropriate antibiotic use3
– May delay receiving appropriate therapy initially
1. Dellit TH et al. Clin Infect Dis. 2007;44:159-177.2. MacDougall C, Polk RE. Clin Microbiol Rev. 2005;18:638-656.3. Available at: http://www.extendingthecure.org/downloads/ETC_FULL.pdf. Accessed April 30, 2007.
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Formulary Restriction: Example
• After initiation of formulary restriction
• Prescribing of third-generation cephalosporins decreased
• Prescribing of cefepime remained relatively stable
• Rates of ceftazidime-resistant Klebsiella pneumoniae decreased
Originally published in Martin C et al. Am J Health Syst Pharm. 2005;62:732-738. ©2005, American Society ofHealth-System Pharmacists, Inc. All rights reserved. Reprinted with permission. (R0727).
250
01998
Gra
ms
per
100
0 P
atie
nt
Day
s
200
150
100
50
12
0
8
10
6
4
2
1999 2001 2002
% C
eftazidim
e-Resistan
tK
Pn
eum
on
iae Iso
lates
2000
Year
Third-Generation Cephalosporins
Cefepime
Ceftazidime-Resistant K Pneumoniae
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Supplemental Strategies ForAntimicrobial Stewardship
• Supplemental strategies
• Clinical pathways and guidelines
• Streamlining/de-escalation
• Dose optimization
• Combination therapy
• Switch from parenteral to oral therapy
• Renal dose adjustments
• Education
• Antimicrobial order forms
• Antibiotic cycling/switch
• Other recommendations
• Working closely with microbiologists
• Physician order entry
Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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Clinical Pathways and Guidelines
• Should be developed with a multidisciplinary team
• Advantages
• May alter prescribing behavior
• Maintains prescriber autonomy
• Disadvantages
• Must have active intervention (participant is notified when not adhering to clinical pathways and guidelines) to be maximally effective
MacDougall C, Polk RE. Clin Microbiol Rev. 2005;18:638-656.
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Clinical Pathways and Guidelines: Example
*Includes only those cases in which the appropriate antibiotic was chosen.
= insufficient data.
South M et al. Med J Austr. 2003;178:207-209.
Appropriate CHOICEof Antibiotic
Appropriate DOSEof Antibiotic*
66
100
80
50
40
30
20
10
0Pre-Card
60
% o
f C
ases
70
90
Post-Card Pre-Card Post-Card
77
19
71
92
78
— —
48
30
81
50
P=.7
P=.028
P<.001P=.001
P<.11
—
Study in Australian pediatric hospital
Physicians received antibiotic guidelines on cards clipped to ID badges
Appropriate choice and dose of antibiotic was evaluated over two 6-month periods
Tonsillitis Pneumonia Orbital/Periorbital Cellulitis
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Streamlining/De-escalation: Therapy
Serious Nosocomial Infection SuspectedSerious Nosocomial Infection Suspected
Begin Empirical Antibiotic (Abx) Treatment With a Begin Empirical Antibiotic (Abx) Treatment With a Combination of Agents Targeting the Most Common Combination of Agents Targeting the Most Common
Pathogens Based on Local DataPathogens Based on Local Data
Pathogen Identified?Pathogen Identified?
Reassess After Appropriate Time FrameReassess After Appropriate Time Frame
Continue Initial TreatmentContinue Initial Treatment
Significant Clinical Improvement After Significant Clinical Improvement After 48-96 Hours of Antibacterial Treatment?48-96 Hours of Antibacterial Treatment?
Deescalate Antibacterials Based on Deescalate Antibacterials Based on Results of Clinical Microbiology DataResults of Clinical Microbiology Data
Search for Superinfection, Abscess Search for Superinfection, Abscess Formation, Noninfectious Cause of Formation, Noninfectious Cause of
Symptoms, Inadequate Tissue Symptoms, Inadequate Tissue Penetration of AbxPenetration of Abx
Discontinue Abx After 7-14 Days Based Discontinue Abx After 7-14 Days Based on Site of Infection and Clinical Responseon Site of Infection and Clinical Response
No
Yes No
Yes
Adapted with permission from Kollef MH. Drugs. 2003;63:2157-2168.
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Streamlining/De-escalation: Example
• Prospective before-and-after study in an intensive care unit (ICU)
• Implementation of a clinical guideline for administration of adequate initial antimicrobial treatment with subsequent reevaluation for potential de-escalation therapy in patients with VAP
Adapted with permission from Ibrahim EH et al. Crit Care Med. 2001;29:1109-1115.
Outcome
Mortality, no. (%)
ICU length of stay, days
Hospital length of stay, days
Secondary VAP, no. (%)
Before Period(n=50)
21 (42.0)
23.1 ± 17.4
39.3 ± 33.1
12 (24.0)
After Period(n=52)
27 (51.9)
21.7 ± 12.9
34.2 ± 26.2
4 (7.7)
Clinical Outcome Measures
P Value
.102
.987
.379
.030
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Dose Optimization
• Takes several factors into account
• Pharmacokinetic/pharmacodynamic (PK/PD)characteristics of the antibiotic
• Patient characteristics
• Causative organism
• Site of infection
Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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%T>MIC
Dose Optimization: PK/PD Parameters
AUC = area under the concentration-time curve; Cmax = maximum concentration; MIC = minimum inhibitory concentration; T = time.
Adapted with permission from Rybak MJ. Am J Infect Control. 2006;34(5 suppl 1):S38-S45.
Time
Cmax/MIC
An
tib
ioti
c C
on
cen
trat
ion
AUC/MIC
PK/PD Parameter Applicable Antimicrobial(s)
Cmax/MIC Aminoglycosides
%T>MIC%T>MIC β-LactamsTetracyclineOxazolidinones
AUC/MIC FluoroquinolonesMacrolidesKetolidesCyclopeptides
Cmax
MIC
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Combination Therapy
• Role in certain clinical contexts
– Used for empirical therapy for critically ill patients at risk of infection with multidrug-resistant pathogens to increase breadth of coverage and likelihood of adequate initial therapy
• Insufficient data to recommend routine use to prevent emergence of resistance
Damas P et al. Crit Care. 2006;10:1-7.Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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Combination Therapy: Example
• Meta-analysis of trials evaluating aminoglycoside/β-lactam combination therapy versus β-lactam monotherapy
• Combination therapy was associated with more superinfections than monotherapy (OR, 0.62; 95% CI, 0.42-0.93)
• Treatment failure was numerically more common for combination therapy than for monotherapy (OR, 0.62; 95% CI, 0.38-1.01)
• No difference in mortality rates between monotherapy and combination therapy groups (OR, 0.70; 95% CI, 0.40-1.25)
Bliziotis IA, Samonis G, Vardakas KZ. Clin Infect Dis. 2005;41:149-158.
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Switch From Parenteral to Oral Therapy
Adapted with permission from Itani KMF et al. Int J Antimicrob Agents. 2005;26:442-448.
Days From Study Medication Start Date
Vancomycin (IV only)
Linezolid (PO, or IV to PO switch)
120
100
80
60
40
20
0 7
% o
f P
atie
nts
Rem
ain
ing
in H
osp
ital
14 21 28 35
P<.01
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Renal Adjustment of Antimicrobials
Evaluating the Patient
• Age
• Body Weight
• Sex
• Dehydration (BUN:SCR ratio greater than 20:1)
• Low muscle mass
• Disease state
• Urine output
• Creatinine Clearance
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Renal Adjustment of Antimicrobials
Assessment of Volume Depletion• Volume depletion can be caused by
-diarrhea, vomiting or diuretics
• Check patient’s BUN:SCr ratio
Normal= 15:1
• If BUN:SCr ratio >20 wait 24 hours and reassess patient
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Creatinine Clearance (CrCl)
• Calculation of Creatinine Clearance can be used to assess renal function
• CrCl calculation is only an estimate of renal function
• Many different methods of calculating estimated CrCl
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Targeted High-use Antimicrobials for Automatic Renal Adjustment
• Cefepime
• Fluconazole
• Levofloxacin
• Piperacillin/Tazobactam
• Imipenem/Cilastatin
• Meropenem
• Automatic adjustment requires physician approved policies and procedures
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Education: Example 1
• Five-year educational campaign to reduce outpatient antimicrobial prescribing introduced in Wisconsin in 1999
• Antimicrobial prescribing rates were compared with Minnesota, a state without a comparable campaign
• Antimicrobial use declined in both states during the study period
• Improved knowledge did not generate greater reductions in Wisconsin
MSA = metropolitan statistical area.Antimicrobial prescribing rate ratios by year and practice location, adjusted for specialty and baseline (1998) prescribing rate. Vertical bars show 95% confidence intervals. Ratio <1 indicates lower antimicrobial prescribing in WI relative to MN.
Adapted with permission from Belongia EA et al. Emerg Infect Dis. 2005;11:912-920.
No Active Intervention
2000 2001 2002 2003 2000 2001 2002 2003
Minneapolis-St. Paul andMilwaukee-Waukesha
MSA
Other Counties in Minnesota
and Wisconsin
0.7
0.8
0.9
1.0
1.1
1.2
1.3
Pre
scri
bin
g R
atio
(W
I : M
N)
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Education: Example 2
• Multitiered campaign to improve rates of appropriate antibiotic use
• Compared the average number of days of unnecessary antibiotic use between the study groups
• Inappropriate antibiotics were discontinued more often in the educational intervention groups (70%) than in the control groups (30%) [no education]
Adapted with permission from Solomon DH et al. Arch Intern Med. 2001;161:1897-1902.
100
90
70
50
30
10
0Target Antibiotics
Inap
pro
pri
ate
An
tib
ioti
cD
isco
nti
nu
atio
n, %
80
60
40
20
Intervention
ControlP=.001
Active Intervention
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Work Closely With the Microbiologist
• Role of microbiologist
• Provides patient-specific culture and susceptibility data to optimize individual antimicrobial management
• Assists infection control efforts in the surveillance of resistant organisms and in the molecular epidemiologic investigation of outbreaks
• Critical role in the timely identification of microbial pathogens and the performance of susceptibility testing
• Responsibilities
– Analyze and present data at least once per year
– Use a sufficient number of isolates to assure accurate data
– Perform and report quantitative and qualitative susceptibility testing
– Conduct group review of data
Dellit TH et al. Clin Infect Dis. 2007;44:159-177.
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Antimicrobial Order Forms
• Can help implement practice guidelines1
PO = orally; qxh = every x hours; IV = intravenously; CVL = central venous catheter.
1. Dellit TH et al. Clin Infect Dis. 2007;44:159-177.2. Bolon MK et al. Pediatr Infect Dis J. 2005;24:1053-1058.
Portion of Antibiotic Order Form Demonstrating How Vancomycin Is Ordered by the Prescriber2
Vancomycin (PO) [$251]125-250 mg/Dose
Vancomycin (IV) [$81]40-60 mg/kg/DAY
PO
IV
12A: Treatment of Clostridium difficile diarrhea after failure of metronidazole or if life threateningq6h
q6hq8hq_h
13A: Suspected pneumococcal meningitis or shunt infection
13B: Serious infections due to β-lactam–resistant Gram-positive organisms
13C: Infections due to Gram-positive organisms in patients with allergy to β-lactam agents
13D:Systemic bacterial endocarditis prophylaxis (see backof form)
13E: Empiric treatment for infection of prosthetic device
13F: Empiric treatment for CVL-related infection with suspicion of Gram-positive organism (eg, cellulitis, positive Gram stain of pus)
1 g
Doseadjustedbased on
levelsand renalfunction
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1. Dellit TH et al. Clin Infect Dis. 2007;44:159-177.2. MacDougall C, Polk RE. Clin Microbiol Rev. 2005;18:638-656.
Antibiotic Cycling/Switch
• Not currently recommended as a routine part of an antimicrobial stewardship program by IDSA guidelines1
• Scheduled removal and substitution of antibiotics (individually or by class) to avoid localized resistance2
• Conflicting evidence on impact2
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1. King WJ et al. BMC Pediatrics. 2007;7:4-10.2. Fischer MA et al. Arch Intern Med. 2003;163:2585-2589.
Local Computer Surveillance andDecision Support
• Can impact antibiotic use1,2
• Can provide benefits to existing antimicrobial stewardship programs
• Key example: physician order entry
• A computer-based system of ordering medication
• Includes interfaces with clinical decision–support systems1
– Provides advice on drug selection, dose, duration
• Based on local surveillance of resistance patterns
Purchasing Power for HealthcarePurchasing Power for Healthcare
Physician Order Entry: Example
• Reduced antibiotic use• Average defined daily dose of IV anti-infectives
decreased, ranging from 9% to 23%, after initiationof POE1
• 37% relative decrease in antibiotic use as a part of bronchiolitis management after introduction of a clinical evidence module into an existing POE system2
• Increased switch from parenteral to oral formulations1
• Decreased prescription errors3,4
• No increase in mortality rates5
1. Fischer MA et al. Arch Intern Med. 2003;163:2585-2589.2. King WJ et al. BMC Pediatrics. 2007;7:4-10.3. van Gjissel-Wiersma DG et al. Drug Safety. 2005;28:1119-1129.4. Colpaert K et al. Crit Care. 2006;10:1-9.5. Keene A et al. Pediatr Crit Care Med. 2007;8:268-271.
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Evaluating Antimicrobial Stewardship Programs
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Patients Whose Treatment Was Managed By
OutcomeAMT
(n=87)ID Fellows
(n=93)Unadjusted OR
(95% CI) P Value
Appropriate 76 44 7.7 (3.7-16.2) <.001
Cure* 49 35 2.4 (1.3-4.5) .007
Failure 13 26 0.5 (0.2-0.9) .03
Evaluating Stewardship Programs: Example 1—Clinical Outcomes
AMT = antimicrobial management team; ID = infectious disease.
*Ten subjects in each group for whom antimicrobial agents were requested for prophylaxis or in whom no evidence of infection was seen when the request was reviewed were excluded.
Adapted from Gross R et al. Clin Infect Dis. 2001;33:289-295.
Comparing Antimicrobial Management byan AMT vs ID Fellows
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Evaluating Stewardship Programs: Example 2—Financial Outcomes
Adapted with permission from Fraser GL et al. In: Owens RC Jr et al, eds. Antibiotic Optimization: Concepts and Strategies in Clinical Practice. Marcel Dekker; 2005:261-326.
Durable Reduction in Antimicrobial Expenditures Associated With the Antimicrobial Stewardship Program at Maine Medical Center
157,000
152,000
142,000
132,000
122,000
117,000
112,0002001 2002 2003 2004
Fiscal Year
Ave
rag
e M
on
thly
Exp
end
itu
re (
$)
Projected Expenditure With 4.5% Inflation, Assuming Use Had Remained Stable
147,000
137,000
127,000
162,000
140,356
134,743
121,437
113,530
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Pharmacoeconomics of Stewardship Programs
• Ruttimann et. al. studied the effects of a multifaceted antibiotic program at an 80-bed tertiary facility
• Over a 4 year time period, the proportion of patients receiving an antibiotic decreases from 46% to 30% (p<0.0001)
• Cost for antibiotics decreased by 56% and total cost of treatment was reduced by 53%
• In theory, the program cost about $20,000 to develop and $20,000 to maintain but no new positions were created
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Pharmacoeconomics of Stewardship Programs
• Bantar et al also instituted and studied a multidisciplinary antimicrobial program over an 18 month period
• The use of antibiotics decreased significantly and yielded a $913,236 cumulative savings
• Decreasing resistance to ceftriaxone among Proteus mirabilis and Enterobacter cloacae and decreasing resistance to methicillin among S. aureus isolates were also observed
• Cost of the program was not studied
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Pharmacoeconomics of Stewardship Programs
• Theobald et al prospectively examined the economic impact of pharmacist-initiated interventions on antibiotics and found approximately a $60/general medicine patient reduction in antibiotic costs (p<0.01).
• LaRocco et al examined the efficacy of concurrent antimicrobial review program at a 120 bed community hospital. This program resulted in an annualized expenditure reduction of $177,000
Purchasing Power for HealthcarePurchasing Power for Healthcare
Gra
ms
per
100
0 P
atie
nt
Day
sEvaluating Stewardship Programs:Example 3—Antimicrobial Resistance
Defined Daily Doses per 1000 Patient Days of Third-Generation Cephalosporins (orange bars) and Cefepime (green bars) Purchased Compared With Ceftazidime-Resistant
Klebsiella Pneumoniae Isolates (dashed line)
250
01998
200
150
100
50
12
0
8
10
6
4
2
1999 2001 2002
% K
leb
siel
la p
neu
mo
nia
e R
esis
tan
t Is
ola
tes
2000
Year
Originally published in Martin C et al. Am J Health Syst Pharm. 2005;62:732-738. ©2005, American Society ofHealth-System Pharmacists, Inc. All rights reserved. Reprinted with permission. (R0727).
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Beyond Antimicrobial Stewardship12 Steps to Prevent Antimicrobial Resistance in Hospitalized Adults
USE ANTIMICROBIALS WISELYUSE ANTIMICROBIALS WISELY 5. Practice antimicrobial control5. Practice antimicrobial control 6. Use local data6. Use local data 7. Treat infection, not contamination 7. Treat infection, not contamination 8. Treat infection, not colonization8. Treat infection, not colonization 9. Know when to say “no” to vanco9. Know when to say “no” to vanco10. Stop treatment when infection10. Stop treatment when infection is cured or unlikely is cured or unlikely
USE ANTIMICROBIALS WISELYUSE ANTIMICROBIALS WISELY 5. Practice antimicrobial control5. Practice antimicrobial control 6. Use local data6. Use local data 7. Treat infection, not contamination 7. Treat infection, not contamination 8. Treat infection, not colonization8. Treat infection, not colonization 9. Know when to say “no” to vanco9. Know when to say “no” to vanco10. Stop treatment when infection10. Stop treatment when infection is cured or unlikely is cured or unlikely
PREVENT INFECTIONPREVENT INFECTION 1. Vaccinate1. Vaccinate 2. Get the catheters out2. Get the catheters out
PREVENT INFECTIONPREVENT INFECTION 1. Vaccinate1. Vaccinate 2. Get the catheters out2. Get the catheters out
DIAGNOSE AND TREATDIAGNOSE AND TREATINFECTION EFFECTIVELYINFECTION EFFECTIVELY 3. Target the pathogen3. Target the pathogen 4. Access the experts4. Access the experts
DIAGNOSE AND TREATDIAGNOSE AND TREATINFECTION EFFECTIVELYINFECTION EFFECTIVELY 3. Target the pathogen3. Target the pathogen 4. Access the experts4. Access the experts
PREVENT TRANSMISSIONPREVENT TRANSMISSION 11. Isolate the pathogen11. Isolate the pathogen 12. Break the chain of contagion12. Break the chain of contagion
PREVENT TRANSMISSIONPREVENT TRANSMISSION 11. Isolate the pathogen11. Isolate the pathogen 12. Break the chain of contagion12. Break the chain of contagion
CDC. Available at: www.cdc.gov/drugresistance/healthcare. Released November 2003.Accessed August 2, 2007.
Prevent InfectionPrevent Infection Diagnose And Treat InfectionDiagnose And Treat Infection
Use Antimicrobials WiselyUse Antimicrobials Wisely
Prevent TransmissionPrevent Transmission