Download Antimicrobial Stewardship: Rationale, Impact

David P. Calfee, MD, MS
February 25, 2013
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
Antimicrobial agents typically account for a
large proportion of the pharmacy expenditures
in a hospital.
A large proportion of hospital patients receive
one or more antibiotics during their hospital
stay.
22.9% in the Netherlands1
 29% among hospitals in 25 European countries2
 37.7% in Trinidad3
 84% in Indonesia4

1Willemsen
3Hariharan
I. Antimicrob Agents Chemother 2007;51:864-7
S. Fundam Clin Pharmacol 2009;23:609-15
2Zarb
4Hadi
P. J Antimicrob Chemother 2011; 66:443-9
U. Clin Microbiol Infect 2008;14: 698-707
Total antibacterial drug use (days of therapy per 1000 patient-days),
ranked from lowest use to highest, during calendar year 2009 in 70 U.S.
academic medical center hospitals.
Polk RE. Clin Infect Dis 2011;53:1100-10
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Patient level

Complications
 Allergy, toxicity, C. difficile infection, vascular access-related
complications
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Prolonged hospitalization
Expense
Antimicrobial resistance
Society level

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Healthcare costs
Antimicrobial resistance

Antimicrobial-resistant infections have been
associated with
Increased medical costs of $6,000-$30,000 (US$)
 Excess duration of hospital stay (6.4-12.7 days)
 Increased mortality

 Attributable mortality of 6.5%.
 The excess mortality results in societal costs of $10.7-$15
million.
Stosar V. Arch Intern Med 1998; 158:522-527.
Cosgrove S. Clin Infect Dis 2003;36: 53-9.
Cosgrove S. Infect Control Hosp Epidemiol 2005;26:166-74.
Roberts RR. Clin Infect Dis 2009;49:1175-84.
Salgado CD. Infect Control Hosp Epidemiol 2003; 24:690-698.
Engemann J. Clin Infect Dis 2003;36:592-8.
Cosgrove SE. Arch Intern Med 2002; 162:185-190.
Cosgrove SE. Clin Infect Dis 2006;42:S82-9.
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It has been estimated that at least 30% of
antimicrobial use in hospitals is inappropriate.
In a study of antimicrobial use during CDI
treatment and for 30 days after treatment:

57% of patients received non-CDI antimicrobials
 77% received at least 1 unnecessary dose of antimicrobial
 26% received only unnecessary therapy
 45% of antimicrobial days included at least 1 unnecessary
antimicrobial
 36% of antimicrobial days included only unnecessary
antimicrobials
Hecker MT. Arch Intern Med 2003;163:972-8
Shaughnessy MK. Infect Control Hosp Epidemiol 2013;34: 109-16
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Use of antibacterial agents for treatment of
syndromes that are not caused by bacteria

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Treatment for culture results that reflect
colonization or contamination rather than infection

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Examples: colds, acute bronchitis, most sore throats, fever
Examples: asymptomatic bacteriuria, skin colonization
Administration of an antibacterial regimen with a
broader than necessary spectrum of activity

Examples: overly broad empiric therapy, failure to narrow
spectrum based on culture results
7
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Prescription of courses of antibacterial therapy for
treatment or prophylaxis that are longer than
necessary
Prescription of antibacterial agents at
inappropriate doses (either too high or too low) or
intervals
Treatment of infectious processes with agents that
do not provide activity against the causative
agent(s)
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Patient-specific factors

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Health care factors

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Age, severity of illness, medical conditions,
immunosuppression
Invasive devices, surgical procedures, antibiotic use,
ICU exposures, length of hospitalization
Health care process factors

Poor hand hygiene, lack of use of barriers,
environmental contamination, crowding, nursepatient ratios, prevalence of pathogen(s), antibiotic
use
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Induction

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Genetic mutation
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Example: Enterobacteriaceae and beta-lactamases
Example: M. tuberculosis and rifampin
Example: Pseudomonas and fluoroquinolones
Acquisition of new genetic material
Conjugation: transfer of genetic material by cell-tocell contact (plasmids, transposons)
 Transformation: acquisition of free DNA
 Transduction: bacteriophages

Treatment with antibiotic X
Bacterium susceptible to antibiotic X
Bacterium resistant to antibiotic X
Neuhauser MM. JAMA 2003;289:885-8
Discontinuation of fluoroquinolone
prophylaxis (6 mo.)
FQ=fluoroquinolone
FQREC=fluoroquinoloneresistant E. coli
Kern WV. Eur J Clin Microbiol Infect Dis 2005;24:111-8
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Coordinated interventions designed to improve and
measure the appropriate use of antimicrobial agents by
promoting the selection of the optimal antimicrobial
drug regimen including dosing, duration of therapy,
and route of administration.
Major objectives of antimicrobial stewardship are:


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To achieve best clinical outcomes related to antimicrobial use
To minimize toxicity and other adverse events
To limit the selective pressure on bacterial populations that
drives the emergence of antimicrobial-resistant strains.
Antimicrobial stewardship may also reduce excessive costs
attributable to suboptimal antimicrobial use.
SHEA, IDSA, PIDS. Infect Control Hosp Epidemiol 2012;33(4):322-7
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Multidisciplinary antimicrobial stewardship
programs have been associated with:
Decreased antimicrobial use (22-36% reductions)
 Reduced rates of antimicrobial resistance among
healthcare-associated pathogens (e.g., Pseudomonas, S.
aureus).
 Reduced incidence of adverse outcomes associated with
antibiotic use (e.g., toxicity, C. difficile infection)
 Significant reductions in pharmacy expenditures

Camins BC. Infect Control Hosp Epidemiol 2009;30:931-8
Patel D. Expert Rev Anti Infect Ther 2008;6:209-22
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
Toth NR. Am J Health Syst Pharm 2010;67:746-9
Martin C, Ofotokun I, Rapp R, et al. Am J Health-Syst Pharm 2005;62:732-8
Davey P, et al. Cochrane Database Syst Rev 2005;19(4):CD003543
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Core strategies
Formulary restriction and preauthorization
 Prospective audit with intervention and feedback
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Supplemental strategies
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Education
Guidelines and clinical pathways
Streamlining or de-escalation of therapy
Dose optimization
Parenteral to oral conversion
Computer-assisted decision support
Others
Dellit TH, et al. Clin Infect Dis 2007;44:159-77
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This strategy is considered to be one of two “core”
strategies of an antimicrobial stewardship
program.
Restricts the use of certain antimicrobials,
requiring “gatekeeper” (e.g., infectious disease
physician or pharmacist) approval for their use.
Preauthorization has been most effective in
reducing antimicrobial use when a dedicated
stewardship team is responsible.
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This strategy is considered to be one of two “core”
strategies of an antimicrobial stewardship
program.
The audit is performed by a physician and/or
clinical pharmacist and addresses:
Appropriateness of a selected agent (based on
microbiologic data, local resistance patterns, evidencebased practice) with recommendation of alternative
therapy, or no therapy, when necessary.
 Potential errors (e.g., allergies, dosing errors, medication
interactions)

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Empiric antimicrobial regimens are often broad in
spectrum in order to maximize the chance of
providing activity against the infecting organism.
Streamlining or de-escalation of empiric therapy can
include:
Adjustment of an empiric antibiotic regimen on the basis of
culture results and other data.
 Discontinuation of empiric therapy if testing subsequently
fails to demonstrate evidence of an infectious process.

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De-escalation limits exposure to broad spectrum
antimicrobial therapy and reduces the cost of
therapy.
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Elligsen M. Infect Control Hosp Epidemiol 2012;33:354-61
Formal review of all
critical care patients
on the 3rd or 10th day
of broad-spectrum
antibiotic therapy
significantly reduced
use of these agents
(p<0.0001).
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Other associated
outcomes:


Increase in susceptibility to
meropenem among gramnegative bacteria (83.4%
versus 78.2%, p=0.03).
31% reduction in nosocomial
C. difficile infections in ICUs
(as compared to a 33%
increase in non-intervention
units, p=0.04).
Elligsen M. Infect Control Hosp Epidemiol 2012;33:354-61
Clinical outcomes for patients treated with aminoglycosides or vancomycin in
hospitals with and without a pharmacist-led antimicrobial stewardship program
Bond CA. Am J Health Syst Pharm 2005;62:1596-605
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Standiford HC. Infect Control Hosp Epidemiol 2012;33:338-45
37% ($3M)
decrease in
antimicrobial costs
over first 3 years
of program.
32% ($2M)
increase in
antimicrobial costs
over 2 years after
program
discontinuation.

Development of evidence-based guidelines and
clinical pathways by a multidisciplinary team can
improve antimicrobial utilization.
Guidelines may provide recommendations for treatment
and/or prophylaxis.
 These guidelines should be based on local epidemiology
and antimicrobial resistance patterns and reflect the
hospital’s formulary.
 Guidelines may also include recommendations for
diagnostic testing, admission criteria, nursing care, and
discharge planning.

The CDI rate decreased significantly after the introduction of the
guidelines and stewardship team (IRR 0.34, p<0.0001)
Talpaert MJ. J Antimicrob Chemother 2011;66:2168-74
OBD=occupied bed-days
There was no
significant
decrease in CDI
rate after
introduction of
enhanced infection
control measures.
CDI decreased
significantly after
introduction of the
antibiotic
intervention
(p=0.007).
Valiquette L. Clin Infect Dis 2007;45 (S2):S112-21
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Dose optimization includes strategies to ensure
that characteristics of the drug, infectious agent,
patient, and site of infection are taken into account.
Such strategies may improve rates of cure and
minimize toxicity. Examples include:

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Prolonged or continuous dosing of beta-lactams
Once-daily dosing of aminoglycosides
Weight-based dosing
Dose-adjustments for patients with renal dysfunction who are
receiving antimicrobials that are cleared by the kidney

This strategy is most commonly used for those
antimicrobial agents with which similar
concentrations are achieved whether administered
intravenously or orally
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
Examples: fluoroquinolones, azoles, metronidazole,
clindamycin, oxazolidinones, trimethoprimsulfamethoxazole)
This strategy can reduce hospital length of stay
and costs, and, potentially, eliminate risks
associated with vascular access.
Protocols for automatic conversion for patients
meeting specific criteria have been successful.
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Education for prescribing clinicians may be a
useful component of a stewardship program but is
most likely to be effective when combined with an
active intervention (e.g., restriction, prospective
audits).
Educational topics should be targeted toward the
audience but may include:
General principles of antimicrobial therapy
 Interpretation of antibiotic susceptibility reports and
hospital antibiograms
 Diagnostic and treatment guidelines and pathways

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Despite evidence of benefit, not all health care
facilities have introduced such programs.
79% of university hospitals
 40% of community hospitals
 Very uncommon in long-term care facilities

Johannsson B. Infect Control Hosp Epidemiol 2011;32:367-74
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Initiating any new program requires a lot of
time and effort.
Resources (human, financial, other) are limited.
Antimicrobial use and antimicrobial resistance
are complex.
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It can seem overwhelming.
Physicians may be resistant to programs that
restrict their autonomy.
The public has misconceptions about
antimicrobial drugs.
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Antimicrobial stewardship programs should be
required through regulatory mechanisms.
Education about antimicrobial resistance and
antimicrobial stewardship must be accomplished.
Research on antimicrobial stewardship is needed.
Antimicrobial use data should be collected and readily
available for both inpatient and outpatient settings.
Antimicrobial stewardship should be monitored in
ambulatory healthcare settings.
SHEA, IDSA, PIDS. Infect Control Hosp Epidemiol 2012;33(4):322-7
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Facility has a multidisciplinary process to review antimicrobial
utilization, local susceptibility patterns, and antimicrobial agents in
the formulary and there is evidence that the process is followed.
Systems are in place to prompt clinicians to use appropriate
antimicrobial agents (e.g., computerized physician order entry,
comments in microbiology susceptibility reports, notifications from
clinical pharmacist, formulary restrictions, evidenced based guidelines
and recommendations).
Antibiotic orders include an indication for use.
There is a mechanism in place to prompt clinicians to review antibiotic
courses of therapy after 72 hours of treatment.
The facility has a system to identify patients currently receiving
intravenous antibiotics who might be eligible to receive oral antibiotic
treatment.
CMS. May 2012. http://www.cms.gov/Medicare/Provider-Enrollment-andCertification/SurveyCertificationGenInfo/Downloads/Survey-and-Cert-Letter-12-32.pdf
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Realize that antimicrobial stewardship is
complex and programs need to be tailored to
the needs and resources of each facility.
Assemble a team.
Identify and prioritize antibiotic use and
resistance issues that need to be addressed.
Identify and take advantage of available
resources.
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Internal and external resources
Clinical champions
Obtain administrative support and buy-in
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Set realistic goals.
Introduce one or more strategies that are most
likely to help you achieve your goals.
Assess your results.
Adjust your approach, if necessary.
Expand your program.
Typical Team Members
Alternative Members
Staff Infectious Disease
Physician*
Infectious Disease Consultant,
Medical Director, clinician
“champion”
Infectious Diseases Clinical
Pharmacist (ID PharmD)*
Other clinical pharmacist,
pharmacy consultant, etc.
Clinical Microbiologist
Laboratory Consultant
(reference lab)
Hospital Epidemiologist
Infection Preventionist
Senior Leadership
Director of Quality, Director of
Nursing
IT personnel
Identify champion prescribing clinician(s).
37
Assessment/planning
Education
Implementation
ASSESSMENT OF CURRENT PRACTICES SURVEY (HOSPITAL)
This questionnaire was developed to better understand your current antimicrobial practices and your
experience with antimicrobial stewardship.
FACILITY NAME:
DATE:
ACUTE CARE FACILITY
1. Is your pharmacy open 24/7?
Yes
No
a. If no, what are the pharmacy’s hours:
b. Please describe the off-hours coverage plan:
c. Antimicrobial use data is provided in (Please check all
that apply):
Amount used (i.e., grams or
milligrams)
Defined Daily Doses (DDD)
Dollars spent
Other (please specify
2. Do you have an in-house microbiology lab?
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
a. If no, where are the microbiology services
performed?
b. How frequently is susceptibility/resistance
information reported to the institution?
c. How are you able to access the data?
d. Are you able to obtain unit-specific data on an asneeded basis?
3. Is an antibiogram developed for your facility? (an aggregation
of sensitivity of organisms)
a. If yes, how often (Monthly, quarterly, annually)?
b. Does your facility have unit-specific antibiograms?
4. Are you currently utilizing computer-based surveillance for
antibiotic use or health care–acquired infections?
a. If yes, please specify the system that is currently in
use.
5. What are the top three common infectious clinical syndromes
at your facility that are either known or estimated?
6. How is information pertaining to infection surveillance
reported (by syndrome, overall incidence within the facility)?
Please list all.
1)
2)
3)
)
ANTIMICROBIAL STEWARDSHIP SURVEY1
Please indicate your agreement or disagreement with the following statements about your institution.
ANTIMICROBIAL RESISTANCE: SCOPE OF THE PROBLEM AND KEY CONTRIBUTORS
1.
Strongly
Disagree
Disagree
Neither
Agree
Strongly
Agree
Strongly
Disagree
Disagree
Neither
Agree
Strongly
Agree
Neither
Agree
Strongly
Agree
Antibiotic resistance is a significant problem in this
institution.
Patient rooms are cleaned according to hospital cleaning
protocol once a multidrug-resistant organism (MDRO)
patient has been discharged.
Adherence to hand-hygiene protocols is excellent at this
institution.
This institution does NOT do enough to control the
development of resistant organisms through surveillance.
This institution does NOT provide adequate staff
education regarding MDROs.
A patient is likely to develop a MDRO infection during
their stay at this institution.
2.
3.
4.
5.
6.
ANTIBIOTIC PRESCRIBING PRACTICES
7.
Microbiology lab results are efficiently communicated to
the treating physician.
I regularly refer to/consider the antibiotic susceptibility
patterns at this institution (e.g., the institutional
antibiogram) when empirically prescribing antibiotics.
If medically appropriate, intravenous antibiotics should be
stepped down to an oral alternative after three days.
Restrictions on antibiotics impair my ability to provide
good patient care.
Antibiotics are overused at this institution.
More judicious use of antibiotics would decrease
antimicrobial resistance.
8.
9.
10.
11.
12.
ANTIMICROBIAL STEWARDSHIP PROGRAMS
(A formal program that monitors and manages the appropriate use of antibiotics.)
Strongly
Disagree
Disagree
13. Antimicrobial stewardship programs improve patient care.
14. Antimicrobial stewardship programs reduce the problem
of antimicrobial resistance.
15. Antimicrobial stewardship programs impact this
institution’s infection rates.
16. This institution has an effective antimicrobial stewardship
program.
1
Antimicrobial Stewardship Survey based on the AHRQ Hospital Survey on Patient Safety Culture.
<http://www.ahrq.gov/qual/patientsafetyculture/hospsurvindex.htm>
PRE-/POST-ASSESSMENT (CLINICIAN SPECIFIC)
GENERAL QUESTIONS PERTAINING TO ANTIBIOTIC STEWARDSHIP
QUESTION
Infectious disease–related hospital-acquired conditions
that the Centers for Medicare & Medicaid Services
(CMS) considers preventable (never events) and for
which reimbursement is limited include:
A. Catheter–associated urinary infections
B. Vascular catheter–associated infections
C. Mediastinitis after coronary artery bypass graft
(CABG) surgery
D. Complicated intra-abdominal infections
What can be considered the most important manner in
which multi-drug resistant organisms (MDROs) increase
costs?
ANSWER
1. A
2. A and B
3. A, B and C
4. All of the above
1. The use of more expensive antibiotics.
2. The expense of personal protective equipment for
isolation precautions.
3. An independent association with increased
morbidity (including length of stay) and mortality.
Routine hospital-approved disinfectant products are
sufficient to kill methicillin-resistant Staph. aureus
(MRSA) in the health care environment.
If a health care worker wears gloves during patient
contact, it is not necessary to perform hand hygiene
afterwards.
4. The cost of follow up to demonstrate clearance of
MDRO carriage.
1. True
2. False
Although no special product is needed to eradicate
vancomycin-resistant enterococci (VRE) or methicillinresistant Staph. aureus (MRSA) from surfaces or
equipment in the hospital, good cleaning technique is
essential.
1. True
2. False
More than 16% of health care workers who wear gloves
during contact with patients colonized or infected with
MDROs become contaminated with the pathogen even
after limited patient contact. Gloves can have
microscopic holes that may allow pathogens to reach
the skin and hand contamination can occur during glove
removal.
ANTIMICROBIAL ASSISTANCE PROGRAM INITIAL REQUEST
Date of approval request:________________________Service:________________Attending:__________________
Contact person and beeper #:_____________________Location:_______________Admit date:_________________
Patient:_____________________________MR#:________________________DOB:_____________Gender:________
Allergies:_____________________________Scr:_________________________Wt(kg):________________________
Underlying Diagnosis:____________________________________________________________________________
INFECTIOUS DX (CIRCLE)
Abscess:____________________
Bacteremia__________________
Bronchitis
Cellulitis (superficial)___________
Cellulitis (deep)_______________
Central line
Cholangitis/cholecystitis
C-diff
Diabetic foot infection
Endocarditis
Endometritis
Esophagitis
Fever and Neutropenia
Fungal infection______________
HIV
Meningitis
Mucositis-thrush
Osteomyelitis
Peritonitis
Pneumonia – CAP
Pneumonia – HAP/VAP
Pneumonia – aspiration
Pre-op prophylaxis
Pyelonephritis
Unknown
UTI
UTI-foley
UTI-nephrostomy
UTI-uretral stent
Sepsis
Notes:
Sinusitis
Surgical wound infection
Transplant__________________
Vaginitis
Other______________________
approved
allergy
FOLLOW-UP? NO
(CIRCLE)
Requested(s) ABX:________________________________________________
_________________________________________________
_________________________________________________
Pertinent Labs:
Pertinent Micro:
Other ABX:
Recommended ABX(s):_____________________________________________
______________________________________________
______________________________________________
Notes:
abx not needed
duplicate therapy
YES
dose-adjustment
IV-PO
alternative agent
drug interactions
ID consult
kinetic consult
DATE______________________
blood cx
sputum cx
urine cx other cx___________
levels
renal fxn
IV to PO
CXR/CHEST CT
appropriate team response?
Other____________________________________________________
other radiology
ANTIMICROBIAL MANAGEMENT PROGRAM FOLLOW-UPS
Date of follow-up______________
Available for F/U: yes
no  pt. D/C
pt expired
ABX D/C
ID CONSULT
Continued therapy with this agent(s) is: (circle one)
1. JUSTIFIED (no further intervention)
2. JUSTIFIED WITH INTERVENTION
3. UNJUSTIFIED
If therapy is UNJUSTIFIED, reason:
1. Organism is not susceptible to agent.
2. Organism susceptible to narrower spectrum/lower
generation agent.
3. Organism is a contaminant.
4. Overlapping spectrum.
5. Prolonged surgical prophylaxis.
6. No drug allergy or mild side effects.
7. Empiric therapy begun awaiting culture results, BUT
no organism isolated after 72 hours.
8. Other_______________________________________
RECOMMENDATIONS
If JUSTIFIED WITH INTERVENTION, recommend:
If UNJUSTIFIED, recommend:
1. IV to PO
1. Alternative antibiotic regimen:
_______________________________________
_______________________________________
2. Dosage change:__________________________
3. Duration change:_________________________
4. Add additional abx:_______________________
2. Discontinuation of antibiotic:
_______________________________________
_______________________________________
5. Streamline regimen/dc other abx
3. ID consult
6. Obtain cultures
4. Other:
7. Check levels
____________________________________
____________________________________
8. Monitoring:______________________________
9. Other:__________________________________
RESPONSE OF PROVIDER
 A
Will
not make change because:
g
r Attending insists on current therapy:

e ____________________________________
e
s Team does not agree with recommend

____________________________________
t
o Other

____________________________________
m
a

GNYHA-UHF Antimicrobial Stewardship Toolkit
www.gnyha.org/6652/Default.aspx
http://www.innovations.ahrq.gov/content.aspx?id=3758

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AHRQ Toolkit for Reduction of Clostridium difficile
Through Antimicrobial Stewardship

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Minnesota Guide to a Comprehensive
Antimicrobial Stewardship Program


http://www.ahrq.gov/qual/cdifftoolkit/cdifftoolkit.pdf
http://www.health.state.mn.us/divs/idepc/dtopics/antibiotic
resistance/mnasp.pdf
UK Guidance for Antimicrobial Stewardship in
Hospitals

http://www.dh.gov.uk/prod_consum_dh/groups/dh_digital
assets/documents/digitalasset/dh_131181.pdf

Dellit TH, et al. Clin Infect Dis 2007; 44: 159-77
IDSA and SHEA Guidelines for Developing an Institutional Program to Enhance
Antimicrobial Stewardship
 http://www.idsociety.org/Antimicrobial_Agents/


Clinical Infectious Diseases 2011;53(Supplement 1)


Infection Control and Hospital Epidemiology 2012;33(4)


Antimicrobial stewardship for the community hospital: practical tools &
techniques for implementation
A special issue devoted entirely to antimicrobial stewardship
Web-based resources
www.cdc.gov
www.idsociety.org
www.shea-online.org
www.sidp.org
www.leadstewardship.org/