Building a Personalized Stewardship Program: Practical

Concepts for Engagement, Design, and Monitoring OutcomeICON Interspecialy ConferencePhilippines – November, 2014

Lance R. Peterson, MD, FIDSA, FASCP, FSHEAEpidemiologist, and vice-Chair of Pathology,

Consultant, Infectious Diseases and MicrobiologyNorthShore University HealthSystem

Clinical Professor, University of ChicagoPritzker 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%, Piperacillin-

tazobactam 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 β–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

M. tuberculosis H. pylori

S. aureus P. aeruginosa

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):S8–S14.

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

• 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)

Solomon DH, et al. Arch Int Med. 2001;161:1897-902.

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

The Evidence for Prospective Audit and Intervention Strategy

• 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)

• 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)

Mehta JM, et al. Inf Contro Hosp Epid. 2014;35:1092-9.

Camins BC, et al. Infect Control Hosp Epidemiol. 2009;30:931-8.

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 neededTamma PD and Cosgrove SE. Inf Dis Clin No America. 2011;25:245-60Kaki R et al. J Antimicrob Chemother. 2011;66: 1223-30B 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 dataB Spellberg. Arch Intern Med 2011;27:171(12):1080-1

Prospective Intervention Program Study

11-22 23-34

Car

bape

nem

Cep

halo

spor

in

Pip

/tazo

No

Pip

/tazo

No

Cep

halo

spor

in

No

Car

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Months 1-10 Patient Specific

Months 11-22 Prioritization

Months 23-34 Restriction

Months 35-44 Mixing

Length and Periods of Usage

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

Therapy determined by a patient-specific

strategy

•Multiple choices

•LOS

•Prior abx exposure

Changed in consecutive patients

following a pre-established schedule

APCarb→Cip→Clin + APCeph→P/T

APCarb, anti-pseudomonal carbapenem; Cip, ciprofloxacin; Clin, clindamycin; APCeph, anti-pseudomonal cephalosporin; P/T, piperacillin/tazobactam.

Adapted from Sandiumenge A, et al. J Antimicrob Chemother. 2006;57:1197-1204. Boucher HW, et al. Clin Infect Dis. 2009;48:1-12.

*P<0.05 compared with the patient-specific period.†<5% of Enterococcus faecalis resistant to vancomycin.

PS=patient-specific period, PP=prioritization period, RP=restriction period, MP=diverse period.

0

2

4

6

8

10

12

14

16

18

20

PS PP RP MP PS PP RP MP PS PP RP MP PS PP RP MP PS PP RP MPAcinetobacter

baumanniiEnterobacteriaceae Pseudomonas

aeruginosaStaphylococcus

aureusEnterococcus

faecalis†

*

***

**

*

*

*

*

*

Posi

tive

isol

ates

/100

adm

issi

ons

Carbapenem-resistant strains

ESBL-producing Enterobacteriaceae

P. aeruginosa resistant to one or more antimicrobials

MRSA

*

Incidence of Patients with Clinical Isolates

More & EqualHeterogeneity

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

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

Measure Patient Specific By Schedule MixingMortality 17% 25% 10%ICU LOS 22 Days 43 Days 26 DaysVent Days 15 24 12

30-Day Vent Free

23 17 21

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.

0

5

10

15

20

25

30

35

40

45

Mar 05-Feb 06 Pre-establishment period

Mar 06-Aug 06 Preperation period

Sep 06-Feb 07 PAMS1 Mar 07-Aug 07 PAMS2 Sep 07-Feb 08 PAMS3

Imipenem groupP/T groupQuinoloneMeropenem Group4GC GroupOthers

Relative Antimicrobial Usage Density (%AUD)

% A

UD

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

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.

Percent of Patients with Gram-negative Bacilli Isolated

0

5

10

15

20

25

30

35

40

% of resistant GNR/GNR

% of resistant P. aeruginosa/GNR

% of MDR GNR/GNR

% o

f p

ati

en

ts i

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cted

wit

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nti

bio

tic-

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ism

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Pre-establishment and preparation period PAMS

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

% of resistant P. aeruginosa/GNR

PAMS, periodic antimicrobial monitoring and supervision

All changes significant at p<0.001

Patient Specific Antibiotic Use - JapanYear 2006 2007 2008 2009 2010 2011 2012 2013

AHI 0.61 0.75 0.78 0.81 0.86 0.83 0.91 0.89

PAMS Patient Specific

Taiwan Symposium, July 2014

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 course - PJ van Duijn and MJM Bonten. Trials 15:277, 2014

Data for Chinese National Campaign• Investigated hospital prescribing during 2011-2012

– Assessed specialized hospitals (maternity, children’s, 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

• 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)

Stewardship Plan (China)

Practical Approaches to Stewardship

• React to a problem• Plan a comprehensive program

– Usually ICU focus

Results of Prescribing in Multiple Studies to Reduce ESBLs

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.

Year Author Agent Reduction in Ceph Use

Replacement agent

Intervention Successful?

1993 Meyer CTZ 73% I/C Yes1996 Rice CTZ 50% P/T Yes1998 Peña 3GC 87% P/T

I/C

Yes

1998 Rahal All Cephs 80% I/C Yes1999 Landman CTX

CTZ

89%

66%

A/S

P/T

Yes

2000 Patterson CTZ 71% (Hosp. A)

27% (Hosp. B)

P/T Yes

2003 Lan 3GC 96% P/T Yes2004 Bantar CTZ 94% P/T Yes2007 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.

40 → 0% ESBLs

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 TherapyWhat is the Evidence?(β-lactam ± aminoglycoside)

• Combination no benefit for sepsisPaul 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 endocarditisFalgas ME, et al. J Antimicrob Chemo 2006;57:639-647. Cosgrove SE, et al. Clin Infect Dis 2009;48:713-721.

• Monotherapy preferred for neutropeniaSchlesinger 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 superinfectionBliziotis IA, et al. Clin Infect Dis 2005;41:149-158.

• No benefit for Gram-negative infectionsPaul 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 + VancomycinCeftaroline

or Tigecycline

Complicated Peritonitis (hospital acquired)

Cefepime +Metronidazole +

VancomycinTigecycline

Complicated Peritonitis (community acquired)

Levofloxacin + Metronidazole Piperacillin/ Tazobactam

MRSA Hospital Acquired Pneumonia (VAP) Vancomycin + Rifampin Linezolid

Neutropenic Fever Ceftazidime + AmikacinPiperacillin/ TazobactamCefoperazone/Sulbactam

Outcome Measurement of Antibiotic Bundle

• Improve Outcome• Mortality• Discharge location• Re-admission

• Improve Safety• Adverse events/Collateral damage

• Reduce Resistance• Lower cost

• Length of stay• Drug cost

McGowan JE, ICHE 2012;33(4):331-337Solomon 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.

AdministrationPayer, Government

Potential Benefits of aDe-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 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.

De-escalation in the ICU:A Retrospective Study

Potential Benefits of aDe-escalation Strategy: Recent Evidence

• ICU-acquired pneumonia in 137 patients:

─ Safe when the patient is clinically stable by day 5

─ Patients in the de-escalation group showed a significantly lower mortality rate compared to patients in the non-de-escalation group

• Day 14, p=0.08• Day 30, p=0.03

(Days)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: 2289–2296, 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 Normalisation–Technical

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: 291–300, 2014

Stewardship Decision Support

• Best Practice Alerts created to facilitate de-escalation– 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 Healthcare-Associated 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 (48%) - RS HUM et al. Appl Clin Inform. 2014 Apr 9;5(2):368-87.

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 SusceptibleBacteria in DiseaseE. coli 350 0.65 227.5K. pneumonia 24 0.54 12.96P. aeruginosa 101 0.03 3.03MSSA 21 1 21MRSA 45 0 0A. baumannii 2 0.45 0.9S. marcescens 11 0.23 2.53P. mirabilis 54 0.76 41.04S. pyogenes 1 1 1E. faecium 23 0.23 5.29E. faecalis 114 1 114B. fragilis 1 1 1Total Number /year 750 % organisms captured = 99.6% total activity of this agent = 57.59705489

Weighted Antimicrobial Choice Calculator

Nosocomial UTI (fictitious numbers)Piperacillin/tazobactam Number/year % Susceptibility Number SusceptibleBacteria in DiseaseE. coli 350 0.98 343K. pneumonia 24 0.87 20.88P. aeruginosa 101 0.95 95.95MSSA 21 1 21MRSA 45 0 0A. baumannii 2 0.66 1.32S. marcescens 11 0.96 10.56P. mirabilis 54 0.97 52.38S. pyogenes 1 1 1E. faecium 23 0.23 5.29E. faecalis 114 1 114B. fragilis 1 1 1Total Number /year 750 % organisms captured = 99.6% total activity of this agent = 89.2075

Weighted Antimicrobial Choice Calculator

Intraabdominal InfectionErtapenem Number/year % Susceptibility Number SusceptibleBacteria in DiseaseE. coli 92 1 92K. pneumonia 44 1 44P. aeruginosa 22 0 0MSSA 7 1 7MRSA 3 0 0Aeromonas 3 0 0Other 12 0.92 11.04P. mirabilis 7 1 7viridans streptococci 44 0.98 43.12E. faecium 1 0 0E. faecalis 3 0 0Enterobacter 20 1 20Total Number /year 750 % organisms captured = 34.4% total activity of this agent = 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 Gram-negative 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 InfectionErtapenem Number/year % Susceptibility Number SusceptibleBacteria in DiseaseE. coli 92 1 92K. pneumonia 44 1 44P. aeruginosa 0 0 0MSSA 7 1 7MRSA 3 0 0Aeromonas 3 0 0Other 12 0.92 11.04P. mirabilis 7 1 7viridans streptococci 44 0.98 43.12E. faecium 1 0 0E. faecalis 3 0 0Enterobacter 20 1 20Total Number /year 750 % organisms captured = 31.46666667% total activity of this agent = 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.

T

Next Generation Rapid Diagnostics• Matrix-assisted laser desorption ionization–time 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 Gram-

negative 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

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

Issue What is Lacking? What can be Done?

Strategic

• Physician participation• Cooperation from colleagues• Network between hospitals and

regional bodies• Community center participation

• Acknowledge effort• Provide information• Improve communication

Operational• Emphasis on diagnostic

procedures in guidelines• De-escalation

• Incorporate community centers in the hospital Antibiotic Stewardship Programs

• Emphasis on diagnosis• Incorporate de-escalation

as a tool

Support Education • Formalize training in antimicrobial use

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):S170-8JL Nagel et al. CID 59(S3):S146-53KA Bauer et al. CID 59(S3):S134-45GM Forrest et al. CID 59(S3):S122-33ESD 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 programThat Includes:

• Considering novel antibiotic prescribing practices to reduce the progression of antimicrobial resistance and improve outcome

Thank You!