Building a Personalized

Stewardship Program: Practical

Concepts for Engagement, Design,
and Monitoring Outcome
ICON Interspecialy Conference
Philippines November, 2014
Lance R. Peterson, MD, FIDSA, FASCP, FSHEA
Epidemiologist, and vice-Chair of Pathology,
Consultant, Infectious Diseases and Microbiology
NorthShore University HealthSystem
Clinical Professor, University of Chicago
Pritzker School of Medicine
Chicago, IL, USA

Objectives
Discuss and present aspects of hospital best
practice for antibiotic stewardship
Guidelines
Evidence for practice

Basics of stewardship programs

Strategies designed to avoid the development
of resistance
What is in the future?

Antibiotic Use in US Acute Care

Hospitals (2011)
Prevalence survey in 10 states for 183 hospitals
5,635 of 11,282 patients (50%) given antibiotics
78% for infection (RTI, UTI, S-STI)
Vancomycin 14%, Ceftriaxone 11%, Piperacillintazobactam 10%, levofloxacin 9%
69% given for community onset infection
82% outside of ICU

Concluded that a need is to understand settings

and indications for appropriate use
How can we limit broad spectrum prescribing?
- S Magill et al. JAMA. 2014;312(14):1438-1446. doi:10.1001/jama.2014.12923

Regional Asia-Pacific Resistance

in 12 Nations (2011)
Broth microdilution on 5,053 strains
37% of S. aureus were MRSA
All susceptible to linezolid, tigecycline and vancomycin

VRE only found in Australia and South Korea

45% of S. pneumoniae resistant to lactams/macrolides
48% of E. coli and 47% of K. pneumoniae were ESBLs
>98% susceptible to colistin and tigecycline; 81-97% susceptible
to carbapenems

P. aeruginosa resistant to >20% of all agents except

colistin
- RE Mendes et al. AAC 57:1521-6, 2013

Antibiotics and Resistance

Annual report on global risks, the World
Economic Forum concluded the greatest risk
. . . to human health comes in the form of
antibiotic-resistant bacteria
For a long-term solution, the answer is not
incremental tweaking of past policies
We need A more innovative form of
stewardship [for] the development of
therapies that do not drive resistance
- B Spellberg et al, NEJM 368:299-302, 2013

Asia-Pacific Leaders View on

Antimicrobial Resistance
For World Health Day (WHO) key government
leaders interviewed to assess awareness and
possible implementation of proposed interventions
12 of 15 participated (5 Philippine participants)
Resistance widely recognized as a problem
Key implementation findings

Lack of coherent plan(s) important

Need for local and National approaches
Lack of reliable financial impact
Need for rational prescription
- Y Lee et al. Globalization and Health 9:(34) 1-7, 2014

Clonal versus Panmictic Evolution

S. aureus

M. tuberculosis

P. aeruginosa

H. pylori

Courtesy of H Grundmann (Bejing 2008)

What is the Goal of

Antibiotic Stewardship?
Optimize clinical outcomes while
minimizing unintended consequences of
antibiotic use
Toxicity
Reduce unintended consequences
Emergence of resistance

Combine with comprehensive infection

control to limit emergence and
transmission of resistance
Reduce health care costs without adversely
impacting quality of care we want to improve
patient care
Dellit TH et al. Clin Infect Dis. 2007;44:159-77

Two Core Antimicrobial

Stewardship Strategies
Prospective audit of antimicrobial use with
intervention and feedback to the
prescriber
Rating: A-I

Formulary restriction and preauthorization

requirements for specific agents
Dellit TH, et al. Clin Infect Dis. 2007;44:159-77.
Jacob JT, et al. Expert Rev Anti Infect Ther. 2010;8:893-902.
Septimus EJ, et al. Clin Infect Dis. 2011;53(S1):S8S14.

The Evidence for Prospective Audit and

Intervention Strategy
Prospective randomized trial for intervention (or
none) involving levofloxacin or ceftazidime
41% reduction for either drug with intervention
No change in length of stay (LOS), readmission, or
mortality
Solomon DH, et al. Arch Int Med. 2001;161:1897-902.
Randomized intervention for antibiotics given 3
days
84% of suggestions accepted; patient cost $400
less
Readmission and mortality rates increased; mean
LOS reduced (20 vs. 25 days), but none
significantly (p = 0.11)

Fraser GI, et al. Arch Int Med. 1997;157:1689-94.

The Evidence for Prospective Audit and

Intervention Strategy
Randomized intervention with antimicrobial use teams
Appropriate use increased: 78% vs. 58% for empirical;
82% vs. 43% for definitive use; 94% vs. 70% for end-use
No difference in mortality; LOS reduced from 8 days to
7 (p = 0.03)
Camins BC, et al. Infect Control Hosp Epidemiol. 2009;30:931-8.
Compared 2 years of Prior Authorization (restriction)
to next 2 years of Prospective Audit with Feedback
55,336 patients (29,660 vs 25,676)
Total use and broad spectrum Gram-negative
therapy increased (p<0.001)
Hospital LOS and LOS after first dose increased
(p=0.016; 0.004)
Mehta JM, et al. Inf Contro Hosp Epid. 2014;35:1092-9.

Multi-Center (5 Hospitals)
Stewardship Intervention
5 academic medical centers in 2003-2004
6 month retrospective baseline, 6 month
intervention, and 6 month follow-up
2 nursing units at each facility
1,265 patients were enrolled in baseline, 1,163 in
the intervention, and 975 in the follow-up period
Used post prescription review and feedback

Use declined at 2 facilities (7%-17%), rose at

2 (12%-15%) and did not change at 1 (2%)
SE Cosgrove et al. ICHE 2012;33:374-80

What is the Current Progress of

Antibiotic Stewardship?

Incorporate multiple strategies within a

given health care facility
Studies show decrease in prescribing
Few have reported even short-term
reductions in antimicrobial resistance
Little data on adverse impact
1187 citations: 24 studies of sufficient quality

3 unblinded randomized trials, 3 interrupted time series,

18 uncontrolled before-after series
More rigorous research is needed
Tamma PD and Cosgrove SE. Inf Dis Clin No America. 2011;25:245-60
Kaki R et al. J Antimicrob Chemother. 2011;66: 1223-30
B Wagner et al. Infect Contr Hosp Epid. 2014; 35:1209-28

Stewardship Cochrane Review

Data review from 1980 through 2009
89 studies with 95 interventions acceptable
Restrictive studies had greatest impact on
use and resistance but effects only
significant for 6 months; not at 1 and 2 years
Decreased prescribing reduced CDI, GNRs
resistant to aminoglycosides/cephalosporins,
MRSA, and VRE
Improved pneumonia treatment lowered
mortality - P Davey et al. The Cochrane Collaboration, The Cochrane
Library, Issue 4, 2013 (http://www.thecochranelibrary.com)

Summary
Much of the past 65 years represents failed
stewardship
Antimicrobial resistance is rapidly worsening
Need to develop successful programs
New programs must be based on practical ideas
well-founded in experimental data
B Spellberg. Arch Intern Med 2011;27:171(12):1080-1

Prospective Intervention
Program Study
Length and Periods of Usage
11-22

Months 35-44
Mixing

No Carbapenem

No Cephalosporin

No Pip/tazo

Prior abx exposure

Months 23-34
Restriction

Pip/tazo

LOS

Cephalosporin

Multiple choices

Carbapenem

Therapy determined
by a patient-specific
strategy

23-34

Months 11-22
Prioritization

Months 1-10
Patient Specific

Changed in
consecutive patients
following a preestablished schedule
APCarbCipClin +
APCephP/T

APCarb, anti-pseudomonal carbapenem; Cip, ciprofloxacin; Clin, clindamycin; APCeph,

anti-pseudomonal cephalosporin; P/T, piperacillin/tazobactam.
Sandiumenge A, et al. J Antimicrob Chemother. 2006;57:1197-1204.

Incidence of Patients with Clinical Isolates

20

* *
18

Carbapenem-resistant strains

Positive isolates/100 admissions

16

More & Equal

Heterogeneity

ESBL-producing
Enterobacteriaceae

14

P. aeruginosa resistant to one

or more antimicrobials

12

MRSA

10

* *
*

*
*

*
*

0
PS PP RP MP

Acinetobacter
baumannii

PS PP RP MP

PS PP RP MP

PS PP RP MP

Enterobacteriaceae

Pseudomonas
aeruginosa

Staphylococcus
aureus

PS PP RP MP

Enterococcus
faecalis

*P<0.05 compared with the patient-specific period.

of Enterococcus faecalis resistant to vancomycin.
PS=patient-specific period, PP=prioritization period, RP=restriction period, MP=diverse period.
<5%

Adapted from Sandiumenge A, et al. J Antimicrob Chemother. 2006;57:1197-1204.

Boucher HW, et al. Clin Infect Dis. 2009;48:1-12.

Clinical Impact Findings

2,621 total patients included
127 episodes of VAP in 119 patients
71% of antibiotic prescribing was for VAP
Adherence to protocol period = 81.3%

Mean outcome measure of clinical impact

Measure

Patient Specific

By Schedule

Mixing

Mortality

17%

25%

10%

ICU LOS

22 Days

43 Days

26 Days

Vent Days

15

24

12

30-Day Vent
Free

23

17

21

Sandiumenge A, et al. Chest. 2011;140:643-651.

Antibiotic Diversity
Program design
12-month period prior to establishment
of Department of Infection Control and
Prevention
6-month preparation period during which
some form of intervention occurred
18 months of Periodic Antimicrobial
Monitoring and Supervision (PAMS)
program divided into three 6-month
periods
Takesue Y, et al. J Hosp Infect. 2010;75:28-32.

Relative Antimicrobial Usage

Density (%AUD)
45
Imipenem group

40

P/T group
Quinolone
Meropenem Group

35

4GC Group
Others

% AUD

30
25
20
15
10
5
0
Mar 05-Feb 06 Preestablishment period

Mar 06-Aug 06 Preperation

period

Sep 06-Feb 07 PAMS1

Mar 07-Aug 07 PAMS2

Sep 07-Feb 08 PAMS3

Relative antibiotic usage density (% AUD) is defined as the cumulative use in defined daily doses of 1
supervised class divided by the cumulative use of all 6 classes.

Takesue Y, et al. J Hosp Infect. 2010;75:28-32.

Percent of Patients with Gramnegative Bacilli Isolated

% of patients infected with antibioticresistant organisms

Pre-establishment and preparation period

PAMS

40
35
30

% of resistant GNR/GNR

resistant
P. aeruginosa/GNR
%%
ofof
resistant
P. aeruginosa/GNR
% of MDR GNR/GNR

25
20
15
10

All changes significant at p<0.001

5
0

PAMS, periodic antimicrobial

monitoring and supervision

Takesue Y, et al. J Hosp Infect. 2010;75:28-32.

Patient Specific Antibiotic Use - Japan

Year 2006 2007 2008 2009 2010 2011
AHI

0.61

0.75

PAMS

Taiwan Symposium, July 2014

0.78

0.81

0.86

0.83

2012

2013

0.91

0.89

Patient Specific

Planned European Trial

Antibiotic rotation (cycling) vs diversity
Cluster-randomized crossover study of mixing
and cycling in 8 ICUs in 5 European countries
During cycling (9 months) cephalosporins,
Piperacillin-tazobactam and carbapenems will
be rotated during consecutive 6-week periods as
the primary empiric treatment
During mixing (9 months), the same antibiotics
will be rotated for each consecutive antibiotic
- PJ van Duijn and MJM Bonten. Trials 15:277, 2014
course

Data for Chinese National Campaign

Investigated hospital prescribing during 2011-2012
Assessed specialized hospitals (maternity, childrens,
stomatological and cancer hospitals)

A total of 105 specialized hospitals in 2011 and 121

specialized hospitals in 2012 were analyzed
Defined daily doses (DDDs) per 100 inpatient days
decreased between 2011 and 2012 from 39.37 to
26.54 DDD/100 inpatient days (p<0.001)
Antibiotic consumption was correlated with the type/
size of hospital, but not with the region
- XX Zou et al. J Huazhong Univ Sci Technol [Med Sci]. 34(3):456-463,2014

ICU Stewardship (China)

Evaluated short-term effects of stewardship:
formulary restriction, preauthorization, quinolone
restriction, and control of total antibiotic
consumption in the ICU at a tertiary hospital
Total consumption in the ICU decreased
Defined daily doses (DDDs) per 100 patient-days
decreased from 197.65 (2011) to 143.41 (2012)

Susceptibility improvement in Enterobacteriaceae

Initial use of no antibiotics or of a single antibiotic
significantly increased (p=0.001)
Use of two antibiotics in combination decreased
(p=0.001)
- D Hou et al. PLOS One. 9; 7: | e101447, 2014

Stewardship Plan (China)

Chinese National plan implemented late

Summer 2012
Maximum number of 50 antimicrobials in General and
Pediatric Hospitals
Maximum of 40 DDD of therapy/100 patient days

NorthShore current use is 60 DDD/100 Patient

Days
- LR Peterson (unpublished data)

Practical Approaches to
Stewardship
React to a problem
Plan a comprehensive program
Usually ICU focus

Results of Prescribing in Multiple

Studies to Reduce ESBLs
Year

Author

Agent

Reduction in
Ceph Use

Replacement
agent

Intervention
Successful?

1993

Meyer

CTZ

73%

I/C

Yes

1996

Rice

CTZ

50%

P/T

Yes

1998

Pea

3GC

87%

P/T
I/C

Yes
40 0% ESBLs

1998

Rahal

All Cephs

80%

I/C

Yes

1999

Landman

CTX

89%

A/S

Yes

CTZ

66%

P/T

CTZ

71% (Hosp. A)

P/T

Yes

2000

Patterson

27% (Hosp. B)
2003

Lan

3GC

96%

P/T

Yes

2004

Bantar

CTZ

94%

P/T

Yes

2007

Lee

3GC

45%

P/T

Yes

Meyer KS, et al. Ann Intern Med. 1993;119:353-359.

Rice LB, et al. Clin Infect Dis. 1996;23:118-124.
Pena C, et al. Antimicrob Agents Chemother. 1998;42:53-58.
Rahal JJ, et al. JAMA. 1998;280:1233-1237.

Landman D, et al. Clin Infect Dis. 1999;28:1062-1066.

Patterson JE, et al. Infect Control Hosp Epidemiol. 2000;21:455-458.
Lan CL, et al. J Microbiol Immunol Infect.2003;36:182-186.
Bantar C, et al. Antimicrob Agents Chemother. 2004;48:392-395.
Lee J, et al. J Antimicrob Chemother. 2007;60:629-637.

Planning

Stewardship Bundles
Bundles are useful in implementing a
multicomponent antibiotic use program
Components should not be dependent on one
another (e.g., want independent actions)
The components can be tracked as process
measures
- E. Dodds-Ashley. Session 68, paper 546. IDWeek2014,
Philadelphia, PA, USA. October 8-12, 2014

A Practical Approach to
the Antibiotic Care Bundle
Obtain proper cultures at infection onset
Use the fewest number of agents as initial therapy that will
treat the likely pathogens
1 broad-spectrum (monotherapy) agent replacing 2 or 3
antibiotics in combination exposes bacteria (normal flora) to 1/2 or
2/3 less antibiotic

Involve pharmacy to use optimal dosing plus route of

administration; treat for the shortest effective time to
obtain a successful outcome
Re-evaluate initial treatment when culture results are
available and no later than the 3rd day of treatment

A Key Issue: Accepted Reasons for

Combination Therapy
Synergy needed for cure
Improve outcome in very sick patients
Prevent development of resistance
Expanded spectrum to cover gaps in
empiric therapy

Historical

Mono- vs Combination Therapy

What is the Evidence?

(-lactam aminoglycoside)
Combination no benefit for sepsis
Paul M, et al. Cochrane Data Sys Rev 2009 (1) Art: CD003344.
Paul M, et al. Brit Med J (2004) doi:10.1136/bmj.38028.520995.63.

Combination no benefit for endocarditis

Falgas ME, et al. J Antimicrob Chemo 2006;57:639-647.
Cosgrove SE, et al. Clin Infect Dis 2009;48:713-721.

Monotherapy preferred for neutropenia

Schlesinger P, et al. Cochrane Data Sys Rev 2003 (4) Art: CD003038.
Paul M, et al. Brit Med J (2003) bmj.com 2003;326:1111.

Combination no benefit to avoid resistance or

superinfection
Bliziotis IA, et al. Clin Infect Dis 2005;41:149-158.

No benefit for Gram-negative infections

Paul M, Leibovici L. Infect Dis Clin N Amer. 2009;23:277-293.

Converting Combinations to Monotherapy

Infection

Combination Agents

Monotherapy

Community-acquired
pneumonia

Ceftriaxone + Azithromycin

Moxifloxacin

Complicated UTI

Ceftriaxone + Gentamicin

Ertapenem or Meropenem

Complicated Skin and

Soft Tissue Infection
(with open wound)

Ertapenem + Vancomycin

Ceftaroline
or Tigecycline

Complicated Peritonitis
(hospital acquired)

Cefepime +
Metronidazole +
Vancomycin

Tigecycline

Complicated Peritonitis
(community acquired)

Levofloxacin +
Metronidazole

Piperacillin/ Tazobactam

MRSA Hospital Acquired

Pneumonia (VAP)

Vancomycin + Rifampin

Linezolid

Neutropenic Fever

Ceftazidime + Amikacin

Piperacillin/ Tazobactam
Cefoperazone/Sulbactam

Outcome Measurement of
Antibiotic Bundle
Improve Outcome
Mortality
Discharge location
Re-admission

Improve Safety
Adverse events/Collateral damage

Reduce Resistance
Lower cost
Administration
Length of stay
Payer, Government
Drug cost
McGowan JE, ICHE 2012;33(4):331-337
Solomon DH, et al. Arch Int Med. 2001;161:1897-902.
Fraser GI, et al. Arch Int Med. 1997;157:1689-94.
Camins BC, et al. Infect Control Hosp Epidemiol. 2009;30:931-8.

Potential Benefits of a
De-escalation Strategy
A reduction in overall antimicrobial costs
Beneficial impacts on the antimicrobial
resistance profile of the institution
Decreased antibiotic-related adverse
events
- Superinfection with resistant bacteria
- Clostridium difficile
No alteration in treatment outcomes
Masterton RG. Crit Care Clin. 2011:27;149-162.

De-escalation in the ICU:

A Retrospective Study
All consecutive patients treated with empiric therapy
in the ICU for 72 hours over a period of 16 months
116 patients with 133 infections
All infections were examined, not just VAP
De-escalation in 60 (45%) of cases
De-escalation therapy was associated with a
significant reduction of recurrent infection
15% vs. 5% (p = 0.02)
De-escalation had no effect on mortality
Morel J, et al. Crit Care. 2010:14;R225.

De-escalation in the ICU:

A Retrospective Study
De-escalation in 45% of cases, and most often
achieved through a reduction in the number of agents:
Decrease in the number of antibiotics: 32% (19
cases)
Reduction of antibiotic spectrum: 8% (5 cases)
Decreased number & reduced spectrum: 35% (21
cases)
Discontinue antibiotic therapy: 25% (15 cases)
Aminoglycosides were the antibiotics most frequently
associated with de-escalation
Morel J, et al. Crit Care. 2010:14;R225.

Potential Benefits of a
De-escalation Strategy: Recent Evidence
ICU-acquired pneumonia in 137
patients:
Safe when the patient is
clinically stable by day 5

(Days)

Patients in the de-escalation

group showed a significantly
lower mortality rate compared
to patients in the non-deescalation group
Day 14, p=0.08
Day 30, p=0.03
Joung MK, et al. Crit Care. 2011:15;R79.

Appropriate Duration of Therapy:

Longer is Not Necessarily Better
Kaplan-Meier estimates of probability of survival in VAP patients
on 8 days vs 15 days of therapy

In ventilator-associated pneumonia, patients treated for 8 days compared to 15 days had:

No excess mortality
No more recurrent infections
Had more antibiotic-free days
Chastre J, et al. JAMA. 2003;290:2588-2598.

Stewardship and Early Discharge

An evaluation audit tool was used to assess
all patients on antibiotic treatment
1,356 patients reviewed; 429 (32%) were
receiving systemic antibiotics
As of result of the treatment review:

99 had antibiotics stopped

47 switched from IV to oral
89 patients were considered ready for discharge
481 bed-days were saved
- M Dryden et al, JAC 67: 22892296, 2012

Impact of Stewardship on SSTI

A retrospective, observational study on impact of
the stewardship on patients admitted to Akron City
Hospital (US) with a diagnosis of SSTI
85 recommendations made for 62 patients, with an
acceptance rate of 95%
The intervention group had a significantly lower
mean length of stay (LOS), and 30-day all-cause
readmission rate
- TR Pasquale et al. Am J Health Syst Pharm. 71:1136-9, 2014

How Can We Improve Practice?

Impact of Infectious Disease

Advice on Antibiotic Prescribing
31 of 3,754 studies suitable for review
Most showed improved prescribing with
reduced antibiotic use (2 did not)
Impact depends on variability of prescribing
practices, seniority of practitioner, and
organizational factors

Computerized decision-support systems may

complement IDS service to decrease
therapeutic uncertainty and increase adequacy
of antibiotic therapy
Not yet formally studied
- C Pulcini et al, Clin Micro Inf. July, 2014 (doi:10.1111/1469-0691.12751)

Information Technology Support

for Stewardship
Three main associations create standards
related to EHRs:
Health Level Seven (HL7)
Comite Europe en de NormalisationTechnical
Committee 215
American Society for Testing and Material E31

Electronic Health Records (EHRs) and

Clinical Decision Support Systems (CDSSs)
benefit clinicians and Antibiotic Stewardship
Programs (ASP)
R Kullar et al. Infect Dis Clin N Am 28: 291300, 2014

Stewardship Decision Support

Best Practice Alerts created to facilitate deescalation
249 created over 18 months
244 acted upon and 70% accepted

Significant reduction in antibiotic use and broad

spectrum use occurred when accepted
- L Schultz et al. Infect Cont Hosp Epid. 34:1259-65, 2013

Algorithms for ICU HealthcareAssociated Pneumonia (HAP)

Belgium hospital assessed 2 algorithm strategies
Local ecology (local antibiogram)
Surveillance cultures

Appropriate therapy was 89% and 88%

Surveillance strategy recommended more narrow
spectrum and less carbapenem use (p<0.001)
- L de Bus et al. Crit Care. 2014 Jul 15;18(4):R152. [Epub ahead of print]

Decision Support for UTI (France)

A multicenter prospective before-and-after
controlled interventional study was conducted
from 19 March to 28 October 2012
912 patients included during 30 week study
The DS was used in 59% of cases (182/307)
DS required patient information input by providers
The DS intervention improved the compliance of
antibiotic prescriptions in only one ED (33% overall)
The DS changed initial diagnosis in 23% of cases, in all
three EDs

The DS partially improved compliance with

guidelines on antibiotic prescriptions in UTIs
- E Domonchy et al. J Antimicrob Chemother doi:10.1093/jac/dku191, 2014

Pediatric Clinical Decision Support

CDS tool for empiric and targeted therapy for
healthcare-associated infections (HAIs) was
developed and incorporated into a commercial
electronic health record (EHR) in two NICUs
Prescribing recommendations were viewed during
only 15% of patient encounters
Most useful features were summarized culture
results (43% used) and antibiotic recommendations
- RS HUM et al. Appl Clin Inform. 2014 Apr 9;5(2):368-87.
(48%)
doi: 10.4338/ACI-2013-09-RA-0069

A passive system requiring data input from

prescribers is likely not optimal

Weighted Antimicrobial
Choice Calculator
Nosocomial UTI (fictitious numbers)
Ampicillin/sulbactam Number/year % Susceptibility Number Susceptible
Bacteria in Disease
E. coli
350
0.65
227.5
K. pneumonia
24
0.54
12.96
P. aeruginosa
101
0.03
3.03
MSSA
21
1
21
MRSA
45
0
0
A. baumannii
2
0.45
0.9
S. marcescens
11
0.23
2.53
P. mirabilis
54
0.76
41.04
S. pyogenes
1
1
1
E. faecium
23
0.23
5.29
E. faecalis
114
1
114
B. fragilis
1
1
1
Total Number /year
750 % organisms captured =
% total activity of this agent =

99.6
57.59705489

Weighted Antimicrobial
Choice Calculator
Nosocomial UTI (fictitious numbers)
Piperacillin/tazobactam Number/year % Susceptibility Number Susceptible
Bacteria in Disease
350
0.98
343
E. coli
K. pneumonia
24
0.87
20.88
P. aeruginosa
101
0.95
95.95
21
1
21
MSSA
0
MRSA
45
0
A. baumannii
2
0.66
1.32
S. marcescens
11
0.96
10.56
P. mirabilis
54
0.97
52.38
S. pyogenes
1
1
1
E. faecium
23
0.23
5.29
E. faecalis
114
1
114
B. fragilis
1
1
1
Total Number /year
750 % organisms captured =
% total activity of this agent =

99.6
89.2075

Weighted Antimicrobial
Choice Calculator
Intraabdominal Infection
Ertapenem
Number/year % Susceptibility Number Susceptible
Bacteria in Disease
E. coli
92
1
92
K. pneumonia
44
1
44
P. aeruginosa
22
0
0
MSSA
7
1
7
0
0
MRSA
3
Aeromonas
3
0
0
Other
12
0.92
11.04
P. mirabilis
7
1
7
viridans streptococci
44
0.98
43.12
E. faecium
1
0
0
0
E. faecalis
3
0
Enterobacter
20
1
20
Total Number /year
750 % organisms captured =
% total activity of this agent =

34.4
86.88372093

When to Expect P. aeruginosa

Retrospective analysis from 4 hospitals
151 patients and 152 controls

P. aeruginosa caused 6.8% of 4,114 episodes of Gramnegative bacteremia

Risk factors: severe immunodeficiency,
OR: age >90, antimicrobials within 30 days, presence of
central venous catheter or a urinary device
If 2, then >25% risk for P. aeruginosa
Schechner V, et al. Clin Infect Dis. 2009;48:580-6.

Weighted Antimicrobial
Choice Calculator
Intraabdominal Infection
Number/year % Susceptibility Number Susceptible
Ertapenem
Bacteria in Disease
92
1
92
E. coli
1
44
K. pneumonia
44
0
0
P. aeruginosa
0
7
MSSA
7
1
0
3
0
MRSA
0
Aeromonas
3
0
11.04
Other
12
0.92
1
7
P. mirabilis
7
44
0.98
43.12
viridans streptococci
E. faecium
1
0
0
E. faecalis
3
0
0
Enterobacter
20
1
20
Total Number /year
750 % organisms captured =
% total activity of this agent =

31.46666667
94.98305085

What About the Future

The WISCA Tool

(Weighted-Incidence, Syndromic, Combination Antibiogram)

C Herbert et al. Infect Control Hosp Epidemiol. 2012;33:381-8.

Next Generation Rapid Diagnostics

Matrix-assisted laser desorption ionizationtime of
flight (MALDI-TOF) decreases the time to
identification by 24 to 36 hours
Prescribing and outcome compared
324 patients with positive CoNS blood culture
No differences in demographics
Patients with true bacteremia were initiated on optimal
therapy sooner in the AST intervention
Decreased mortality seen (21.7% vs 3.1%, p=0.023)

AST group with contaminated CoNS had

decreased inappropriate prescribing and
decreased serum vancomycin trough assays
- JL Nagel et al. J Clin Micro. 2014, 52(8):2849. DOI: 10.1128/JCM.00682-14

More Next Generation Diagnostics

153 patients with antibiotic-resistant Gramnegative bacteremia compared to 112 patients
treated post-implementation
Rapid diagnostics improved time to optimal
therapy (80.9 h vs 23.2 h; p<0.001)
Pre-intervention patients had increased LOS (23.3
days vs 15.3 days, p<0.0001)
Mortality among patients during intervention
period was lower (8.9% versus 21%, p<0.01)
Mass spectrometry for rapid diagnosis with
significantly improved outcomes and reduced cost
- KK Perez et al. J Infect (2014), 1e10. http://dx.doi.org/10.1016/j.jinf.2014.05.005

Overcoming Barriers to Stewardship

Issue

What is Lacking?

Strategic

Operational

Support

What can be Done?

Physician participation
Cooperation from colleagues
Network between hospitals and
regional bodies
Community center participation

Emphasis on diagnostic
procedures in guidelines
De-escalation

Education

Acknowledge effort
Provide information
Improve communication

Incorporate community
centers in the hospital
Antibiotic Stewardship
Programs
Emphasis on diagnosis
Incorporate de-escalation
as a tool

Formalize training in
antimicrobial use

Bal AM, et al. Curr Opin Infect Dis. 2011;24:357-62.

Broad Approaches to Implementation

Legislation mandating stewardship
Ill defined approaches on what to do

Need to involve administrators to improve

economic, process, and outcome measures
Rapid diagnostics can provide opportunities
Electronic Health Records and Clinical Decision
Support have potential for enhancement
Stewardship can be more credible by refocusing
on specific disease states and measuring
usefulness in quality and safety efforts
KK Trivevi et al. CID 59(S3):S170-8
JL Nagel et al. CID 59(S3):S146-53
KA Bauer et al. CID 59(S3):S134-45
GM Forrest et al. CID 59(S3):S122-33
ESD Ashley et al. CID 59(S3):S112-21

The Bottom Line:

Infection control policies and
optimization in the use of (already
existing) molecules (antimicrobials)
are still the most effective approaches
to reduce the spread of resistance and
preserve the activity of antimicrobials
Bassetti M et al. Expert Rev Anti Infect Ther. 2011;9:909-922

Summary: Antibiotic Stewardship

Lack of agents against resistant bacterial
pathogens will continue well into the future
There is a need to initiate an effective and
comprehensive infection control program
That Includes:
Considering novel antibiotic prescribing
practices to reduce the progression of
antimicrobial resistance and improve
outcome

Thank You!