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Today’s topic

Defeating Superbugs: Hospitals on the Front Lines

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Dr. Robert WeinsteinChairman, Department ofMedicine, Cook CountyHealth and HospitalsSystem; professor, Rush University MedicalCenter, Chicago

Dr. Lance PetersonDirector, ClinicalMicrobiology and InfectiousDisease Research Division,NorthShore UniversityHealthSystem, Evanston, Ill.

Dr. Anurag MalaniMedical director, Infection Prevention and Antimicrobial Stewardship Programs,St. Joseph Mercy Hospital,Ann Arbor, Mich.

Maureen McKinneyEditorial programs manager,

Modern Healthcare

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HousekeepingHousekeeping1. Viewer Window 2. Control Panel

Dr. Anurag MalaniMedical director, Infection Prevention and Antimicrobial

Stewardship Programs, St. Joseph Mercy Hospital,Ann Arbor, Mich.

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What is Antimicrobial Stewardship?

“The selection of the optimal antimicrobial

agent, route of administration, dose, and

duration to provide maximal clinical benefit,

while minimizing unintended consequences.”

Why Antimicrobial Stewardship?

• Up to 50% of abx use is inappropriate • High quantity, poor quality

• Inappropriate and unnecessary abx use can lead to selection of resistant pathogens

• Antimicrobial resistance continues to increase

• Emergence of antimicrobial resistance leads to significant impact on pt morbidity & mortality, health care costs

Dellit TH, et al. Clin Infect Dis 2007;44:159-77

How We Acquire Antibiotic Resistant Organisms in Hospitals

Paterson DL. Clin Infect Dis 2006;42:S90-5

Resistance: A Public Health Crisis

www.cdc.gov/drugresistance/healthcare

Antimicrobial Resistance Continues to Increase

Wenzel et al. Infect Cont Hosp Epi 2008;29:1012-8

Increase of Carbapenem-Resistant Enterobacteriaceae

(CRE) Infections

KPC-producing CRE in the U.S. - 2014

http://www.cdc.gov/hai/organisms/cre/TrackingCRE.html

Urine Culture Showing CRE

Antibacterials Approved by the FDA, 1983 - 2007

Spellberg B et al. Clin Infect Dis. 2008;46:155-164

Impending Crisis of New Antibiotics

• Last new class of drugs active against GNB, in

the 1970s, – “Trimethoprim”

• No new classes of antimicrobials in the

foreseeable future

• No new drugs to deal with multi-resistant GNB

until 2018

• WHO – “Antibiotic resistance” as one of major

threats to human health

1. Bartlett J. Clin Infect Dis 2011;53:S4. 2. http://www.ecdc.europa.eu/en/publications/Publications/Forms/ECDC_DispForm.aspx?ID=444.

Controlling Resistance?

• A combination of BOTH

– Effective antimicrobial stewardship program

AND

– Comprehensive infection control program

– Have been shown to limit the emergence and

transmission of antibiotic resistant bacteria

Dellit TH, et al. Clin Infect Dis 2007;44:159-77

Antimicrobial Stewardship Works

Valiquette L, et al. Clin Infect Dis 2007;45:112-121

Impact of a Reduction in the Use of High-Risk Antibiotics on the Course of an Epidemic of

Clostridium difficile-Associated Disease Caused by the Hypervirulent NAP1/027 Strain

Antimicrobial Stewardship Reduces Costs

Standiford H, et al. Infect Cont Hosp Epi 2012;33:338-46.

Antimicrobial Stewardship Program Goals

• Ensure appropriate antimicrobial use

- Optimal selection, dose, duration

• Reduce or attenuate advancing antimicrobial resistance

• Improve patient outcomes and reduce adverse events

related to antimicrobials

- Decrease Clostridium difficile infection

- Decrease morbidity and mortality

- Decrease length of stay

• Decrease healthcare expenditures and antimicrobial

costs

Dellit TH, et al. Clin Infect Dis 2007;44:159-77Ohl CA. Seminar Infect Control 2001;1:210-21

Antimicrobial Stewardship Interventions

• Prospective audit with intervention and feedback

• Formulary restriction and preauthorization

• Education

• Streamlining and de-escalating

• Dose optimization

• Guidelines and clinical pathways

• Parenteral to oral conversion

Dellit TH, et al. Clin Infect Dis 2007;44:159-77

Antimicrobial Stewardship Partners

Information Technology

Clinical Pharmacists

Infection Control

Microbiology Lab

Clinicians & Residents

ID Physicians & Fellows

Abx SubcommitteePharmacy and Therapeutics Committee

AdministrationAntimicrobial

Stewardship Team

SJMAA Antimicrobial Stewardship Program

• Initiated in 2009– 2 ID physicians, 3 ICU pharmDs

• Focus on restricted abx- New starts, duration

• Interventions

- Approve

- Stop abx

- Change/Narrow abx

- Obtain ID Consult

- Against ASP advice

SJMAA Antimicrobial Stewardship Program

Outcomes from SJMAA ASP Year One

Demographic and clinical characteristics and outcomes

of patients pre-ASP compared to patients post-ASP

Multivariable analysis for associationof ASP and patient outcomes

Malani AN, et al. Am J Infect Control 2013;41:145-8.

Flow Diagram of Outcomes from ASP

Malani AN, et al. Am J Infect Control 2013;41:145-8.

FY 2009 FY 2010 FY 2011 FY 2012Percent Change

Antimicrobial

agents total costs1,503,748 1,274,837 1,231,079 1,221,275

-18.8

(-784,053)

Total patient days 147,955 144,783 146,332 146,310

Antimicrobial

costs per patient

day (average)

10.16 8.81 8.41 8.35 -17.8

Targeted

antimicrobial

agents

462,404 297,851 278,998 342,997-25.8

(-467,360)

Antimicrobial Costs by Fiscal Year

Improving Antibiotic Use Reduces Rates of C. difficile

0

2

4

6

8

10

12

14

2008 2009 2010 2011 2012 2013

Ca

se

s p

er

10

,00

0 P

t D

ays

HO-CDI

Two-step testing

PCR testing

Initiation of ASP

Current State of Stewardship

• Track all restricted antimicrobials

• Track all antimicrobials in high risk pts

• Use software for surveillance, tracking, clinical decision support

• Development of bundles for specific infections/syndromes

• Use of antimicrobial timeouts and rapid diagnostic testing

• Lead quality initiatives related to abx use (i.e. SCIP)

Clostridium difficle Infection Powerplan

Antimicrobial Management Page

Summary

• Primary mission of ASPs is patient safety

• Goals of ASPs are to ensure that there are

systems and support to help providers use

antibiotics optimally

• ASPs can improve pt outcomes, reduce tx costs,

reduce CDI, & reduce or slow the development

of resistant organisms

• ASPs can and must be implemented across

continuum of care

Dr. Robert WeinsteinChairman, Department of Medicine, Cook County

Health and Hospitals System; professor,Rush University Medical Center, Chicago

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TOPICS

• Scope of Multidrug Resistant Organisms

(MDROs)

• MDRO Resistance Iceberg and Networks

• Impact of a Control Bundle on CRE

• Lessons Learned

http://www.cdc.gov/drugresistance/threat-report-2013/

Adapted from Weinstein & Kabins, Am J Med 1981; 70:449-54.

RESISTANCE “ICEBERG”

Infections Control Measures

Are Based on Epidemiology

Legend

LTACH

Nursing Home

Acute Hospital

Patient

Carbapenem Resistance: Hospital and

Long-term Care InterrelationsSocial Network depiction

of LTACH, Nursing Home,

& Hospital spread of

Carbapenem-resistant

Klebsiella pneumoniae

LTACH, Long term acute care

hospital; MDRO, Multidrug

resistant organism

Won et al, Clin Infect Dis 2011; 53(6):532-40.

Wiener et al, JAMA 1999; 281:517-23.

These Interrelations Are Not A New Problem

Vernon et al, Arch Intern Med 2006; 166:306-12.

Source Control of MDROs — Remove the Fecal Patina

MDRO, Multi-drug resistant organism

Vernon et al, Arch Intern Med 2006; 166:306-12.

Risk Ratios for Skin Contamination and Environmental or Healthcare Worker Contamination by or

Patient Acquisition of VRE

VRE, Vancomycin-resistant enterococci

Before After

Kindly provided by Mary K. Hayden, MD

CRE, Carbapenem-resistant Enterobacteriaceae

Axillary Cultures for CREs Before and After

Chlorhexidine Bathing

Munoz-Price et al, Infect Control Hosp Epidemiol 2010; 31(4):341-7.

MDRO, Multi-drug resistant organism

Long-term Care MDRO Control Bundle

Monthly distribution of patients with KPC-positive clinical isolates or admission surveillance cultures is shown.

January's and April’s isolates were probable KPC producers (on the basis of phenotype); all other isolates were

confirmed to produce KPC by means of polymerase chain reaction. Stars indicate 1 patient (depicted by these 2

rectangles) who was found to be a KPC carrier at admission and then 6 days later was found to have KPC-positive

Klebsiella pneumoniae in clinical cultures of urine and sputum samples.

Epidemiologic Curve of Patients Colonized with K. pneumoniae Carbapenemase (KPC)–producing Gram-negative Rods at a Long-term Acute Care Hospital

• Daily 2% chlorhexidine cleansing of all patients

• Admission surveillance cultures

• Serial point prevalence surveillance

• Contact precautions

• Personnel training

• Enhanced environmental cleaning

Munoz-Price et al, Infect Control Hosp Epidemiol 2010; 31(4):341-7.

LESSONS LEARNED

• Antibiotic Resistance — A BIG and CONTINUING problem

• Control needs regional approach and support from the top

• Bundles can control emerging resistance — for CRE & KPC

– Daily cleansing of all patients with chlorhexidine

– Surveillance culturing

– Cohorting and/or single room nursing with contact precautions

– Enforcing HAND HYGIENE

• We can control problems; is there potential to eliminate

resistance?

CRE, Carbapenem-Resistant Enterobacteriaceae;

KPC, Carbapenemase-producing Klebsiella pneumoniae

Dr. Lance PetersonDirector, Clinical Microbiology and Infectious Disease

Research Division, NorthShore University HealthSystem,Evanston, Ill.

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Potential COI

• Research Grants

– AHRQ, BD GeneOhm, CDC, Cepheid, GeneWeave, NorthShore, MicroPhage, Nanogen, Nanosphere, NIAID, Pfizer, Rempex, Roche, 3M, Washington Square Health Foundation

• Consultations (in conjunction with research

projects and new diagnostics)

– BD GeneOhm, Cepheid, Merck, Pfizer, Roche

Objectives

• Review the progress in MRSA control using active surveillance testing (AST)

• Insights from analyzing scientific reports

– Granular understanding the biology of Infection Control

• Discuss Control of MRSA in Long Term Care

Why Care About MRSA?

US Infection Mortality 2005

FR DeLeo &HF ChambersJCI 119:2464, 2009

Clonal versus Panmictic Evolution

M. tuberculosis H. pylori

S. aureusS. aureus P. aeruginosaP. aeruginosa

Courtesy of H Grundmann (Bejing 2008)

Why Look for MRSA Carriers?

Colonized Patients Spread MRSA• Compared 58 patients with MRSA disease to

57 with nasal colonization to determine risk for skin and environmental contamination

– Skin and environment contaminated 50 vs 47%

– Various skin sites 38-66% vs 30-63%

– Various environment sites 27-60% vs 21-63%

• Glove acquisition from skin 14-45% vs 16-38%

• “Strategies to limit transmission must address colonized patients”

S Chang et al. CID 48: 1423-8, 2009

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

8/03 - 7/04 9/04 - 7/05 9/05 - 7/06 8/06 - 7/07 8/07 - 7/08 8/08 - 7/09

Pre

vale

nce D

en

sit

y

Years

Total MRSA Healthcare Infections

Total

ICU surveillance Universal surveillance

P = 0.15

P ≤ 0.001

70% reduction intotal MRSA diseaseduring hospitalization and 30 days post-discharge

(Cases/1

0,0

00 p

ati

en

t-d

ays)

LR Peterson et al. Decennial Meeting on Nosocomial Infections, Atlanta, 2010

2 BSI in 4 hospitals

A Robicsek et al. Ann Int Med 148:409-18, 2008

VA Healthcare Continued Program

• Between 2007 and 2010 there was a 38% increase in the number of hospitals with no MRSA infections SM Kravolic et al. AJIC 41:456-8, 2013

p<0.0001 fromstart to end

Can We Afford MRSA Control?

How Much Does MRSA HAI Cost?

Mean Total Cost

95% CI Mean Profit/Loss 95% CI

No MRSA HAI (n=5796)

LOS ≥8d

$50,013 $42,363, $57,662

-$25,000 -$28,883, -$21,116

MRSA HAI

(n=178)

$73,795 $63,743, $83,847

-$35,479 -$42,034, -$28,923

Excess $23,783 $16,771, $30,794

-$10,479 -$16,110, -$4,848

LR Peterson et al. Jt Com J Qual Pt Safety 33:732-8, 2007

Medical and Economic Outcome

• Excess expense of MRSA infection (compared to no infection) = $24,000

• The first 8 years of NorthShore MRSA containment program prevented 813 infections

– Net direct benefit from medical expense reduction is over $16 million ($2M/Year)

– Number of deaths avoided = 144 (18/Year)

LR Peterson. JCM 48:683-9, 2010LR Peterson et al. Jt Comm J Qual Patient Saf 33:732-8, 2007RM Klevens et al. JAMA 298:1763-71, 2007

Prospective Validation, Sept-Nov 2011

For a preventable infectious disease, testing cost declines with time

What About Conflicting Literature – Practices that Impact Results?

Over 10,000 articles on antimicrobial

resistance published in the last half-century

Predictors of Program Success

L Peterson, JCM, 48:683-9, 2010

Author MRSA

Prevalence

Mean Length of

Hospital Stay

Test

Sensitivity

Time to

Result

Reporting

Length of

Intervention

Period

Estimated

MRSA Days

Captured

Program was

Successful

Harbarth et al 6.7% 3.7 to 4 days 84% ≥22.2 hours 5 to 17 months 63% No reduction in

disease

Harbarth et al 5.1% 6.4 days 84% ≥22 to23 hours 9 months 72% No reduction in

disease

Robicsek et al 6.3% 4.6 days 98% 15 hours 21 months 85% Reduction in

disease with

universal

surveillance

Jeyaratnam et al 6.7% 3.8 days 87.8% ≥22 hours 5 months 67% No reduction in

transmission or

disease

Hardy et al 6.3% 7.2 days 98% 22 hours 8 months 86% Reduction in

transmission

Hardy et al 5.2% 6.5 days ≤73% 42 hours

(direct culture)

8 months 53% No reduction in

transmission

Bowler et al 14.6% > 1 year 80% 48 hours 2 years 80% Reduction in

disease

Disease reduced with pre-emptive isolation

Daily Chlorhexidine Bathing

• Multicenter, non-blinded cluster randomized trial to assess effect on MDRO acquisition and BSI HAI in 9 ICUs and a BMT unit

– Chlorhexidine (2%) or plain cloth for 6 months and then switch for 6 months on 7,727 patients

• MDRO acquisition was 23% lower (p=.03)

– No difference for MRSA acquisition (p=.29)

• All BSI was 28% lower with chlorhexidine (p<.01)

– 6.6 vs 4.8 BSI/1,000 patient days (ᴧ due to CLABSI)

– Difference due to CNS (p<.01), not MRSA, GNR or fungi MW Climo et al. NEJM 368:533-42, 2013

What About Decolonizing Everyone?NEJM Results NS Results Comments

Scope/Population 18 months/29 ICUs101,600 patient days

38 months/4 ICUs55,350 patient days

Similar hospitaltypes

Outcome No screening and Decolonize all

Screen all and only Isolate positives

Rate of MRSA clinical isolates

2.1 per 1,000 patient days

0.3 per 1,000 patient days

NS data based on 342,000 patients

Rate of all cause ICU bacteremia

3.6 per 1,000 patient days

1.0 per 1,000 patient days

In ICU NS is >3-fold lower

Rate of MRSA bacteremia

0.47 per 1,000 patient days

0.018 per 1,000 patient days

In ICU NS is >25-fold lower

Cost $40 per patient* $27-$37 per patient (includes all MDROs)

NS cost range based on test price

*Range of prices for 5 days of Bactroban Nasal® from 11 on-linepharmacies is $116.15-$120.45, making the $40 estimateproblematic (http://www.goodrx.com/bactroban-nasal);last accessed June 7, 2013)

S Huang et al. NEJM May 29, 2013KE Peterson et al. ICHE 33:790-5, 2012A Robicsek et al. ICHE 32:9-19, 2011A Robicsek et al. Ann Int Med 148:409-18, 2008LR Peterson et al. Jt Comm J Qual Patient Saf 33:732-8, 2007

Illinois Summary (2012)Public Reported MRSA Infection Rates

Trends in methicillin-resistant Staphylococcus aureus (MRSA) in Illinois based on Hospital Discharge Data, 2009-2012. Illinois Department of Public Health. http://www.healthcarereportcard.illinois.gov/files/pdf/mrsa_2012_Trends.pdf

L Peterson, unpublished data

Does My Hospital Have a MRSA Problem?

• Calculate your own MRSA BSI MRSA rate

– A = number of persons > 2 days after admission in one year with MRSA BSI

– B = number of annual patient days

• A/B times 10,000 = Annual MRSA BSI HAI rate per 10,000 patient days

• If over 0.1, then consider if improvement(s) can be made

MRSA in Long Term Care

• Study of MRSA control in 3 LTCFs

• Performed surveillance testing and decolonized positive persons (no isolation)

• 16,773 swabs over 2 years

LR Peterson et al. Funded by the AGENCY FOR HEALTHCARE

RESEARCH AND QUALITY (Grant R18 HS19968 award)

Period MRSA

Infections

PD Rate/1000 PD p Value

Baseline 44 365,809 0.120 ref

Year 1 23 294,165 0.078 (35% ↓) =0.09

Year 2 12 287,847 0.042 (65% ↓) <0.001

Summary of EvidenceView of LP

• Majority of the evidence supports

– MRSA clinical infection remain important

– Surveillance and isolation or decolonization if the goal is to reduce MRSA disease

• Majority of the evidence refutes

– Hand hygiene alone can prevent MRSA transmission and subsequent disease

– Universal chlorhexidine decolonization can reduce MRSA clinical disease

The NorthShore Program

Today’s panelists...Defeating Superbugs: Hospitals on the Front Lines

During today’s discussion, feel free to submit questions at any time by using the questions box.

Maureen McKinneyEditorial programsmanager,Modern Healthcare

Dr. Lance PetersonDirector of the Clinical

Microbiology and InfectiousDisease Research Division,

NorthShore UniversityHealthSystem,

Evanston, Ill.

Dr. Anurag MalaniMedical director,

Infection Prevention andAntimicrobial

Stewardship Programs, St. Joseph Mercy Hospital,

Ann Arbor, Mich.

Dr. Robert WeinsteinChairman, Department ofMedicine, Cook CountyHealth and HospitalsSystem; professor, Rush University Medical Center, Chicago

TODAY’S MODERATOR

Thank you...... for attending today’s editorial webinar on the role of hospitals in the battle against superbugs.We also thank our panelists, Dr. Anurag Malani, medical director of the Infection Prevention and

Antimicrobial Stewardship Programs, St. Joseph Mercy Hospital, Ann Arbor, Mich.; Dr. Lance Peterson,director of the Clinical Microbiology and Infectious Disease Research Division at NorthShore University

HealthSystem, Evanston, Ill.; and Dr. Robert Weinstein, chairman of the Department of Medicine,Cook County Health and Hospitals System, and professor at Rush University Medical Center, Chicago.

Expect a follow-up e-mail within two weeks. For more information,send an e-mail to webinars@modernhealthcare.com

Register now for Modern Healthcare’s next virtual conference, “Building Tomorrow’s Delivery Model,” set forWednesday, Oct. 15. For more information, please visit modernhealthcare.com/building