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Intermountain APIC and Qualis Health

present

I-APIC HAI Prevention Learning Network Webinar Series

Antimicrobial Stewardship in Infection Prevention

May 9, 2012

Julia Moody MS, SM(ASCP)Director, Infection Prevention

Clinical Services Group

HCA, Inc., Nashville, TN

Slide: 2

Objectives• Discuss the urgent need and value for antimicrobial stewardship

programs

• Review the current state of antimicrobial resistance patterns and issues related to resistance.

• Recognize impact of resistance on population/patient health

• Discuss global-to-local program strategies for decreasing antibiotic resistance

• Clarify day-to-day infection preventionist duties related to antimicrobial stewardship

• Describe how to participate or lead planning and implementation of appropriate antimicrobial stewardship strategies in various healthcare settings

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Case Study: “How Hardwired are your Infection Prevention Practices?”

• 35yo ventilator dependent quadrapalegic is a frequent readmission; and this stay is from LTACH (long term acute care hospital) to acute care hospital MICU with pneumonia due to Pseudomonas aeruginosa resistant to all antibiotics except for amikacin

• Pharmacy indicates Amikacin is not available due to a nation wide drug shortage; colistin susceptibility pending

• Bed supervisor calls infection prevention for guidance

• Preventing transmission of this resistant MDRO is reliant on highly compliant infection prevention practices

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Colonized and infected patients are links in the chain of MDRO transmission between

neighboring healthcare settings

Ambulatory Care settings

Acute carehospitals Skilled nursing

facilities

Colonized or recently Infected patients

Older individualsIn community

Acute carehospitals

Skilled nursing facilities

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Magnitude of Antimicrobial Use

• Antibiotics are the second most commonly used class of drugs in the United States

• More than 8.5 billion dollars are spent on anti -infectivesannually

� 200-300 million antimicrobials prescribed annually

� 53% for outpatient use

• 30-50% of all hospitalized patients receive antibiotics

• Studies estimate up to 50% of antibiotic use is either unnecessary or inappropriate across all type of health care settings

Clin Infect Dis 2007; 44:159-177

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192 187

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Duration of Therapy

Longer than Necessary

Noninfectious or

Nonbacterial Syndrome

Treatment of

Colonization or

Contamination

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Unnecessary Use of Antimicrobials in Hospitalized Patients

• Prospective observational study in ICU

• 576 (30%) of 1941 antimicrobial days of therapy deemed unnecessary

Hecker MT et al. Arch Intern Med.

2003;163:972-978.

Most Common Reasons for Unnecessary Days of Therapy

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Why Improve Antimicrobial Use?

• Antimicrobial agents are misused in hospitals

• Antibmicrobial misuse adversely impacts patients and society

• Antimicrobials are the only drug where use in one patient can impact the effectiveness in another.

• Improving antimicrobial use improves patient outcomes and saves money

• Improving antimicrobial use is a public health imperative

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Antibiotic Development

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Antimicrobial Agents Opportunities • Reduce overuse and misuse

– Given when not needed

– Drug/bug mismatch and is the wrong antibiotic for treatment

– Given at the wrong dose-renal and weight-based dosing

– Broad spectrum agents are used to treat very susceptible bacteria-de-escalation

• Impact of overuse and misuse on healthcare

– Increases mortality and morbidity

– Antimicrobial resistance is accelerated by excessive use of antibiotics

– Antibiotic-resistant infections have been estimated to cost the US healthcare system over $20 billion annually

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Hospital and Societal Costs of Antimicrobial-ResistantInfections in a Chicago Teaching Hospital:

Implications for Antibiotic StewardshipCLIN INFECT DIS 49(8):1175-1184.

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Case Study

• 56 year old white female admitted with hypotension, fever, and flank pain. Her urine showed pyuria and bacteriuria, the peripheral WBC was 16,000. She was admitted to the ICU and empirically started on cefepime.

• On day 2, urine and blood grew E. coli sensitive to all tested antibiotics except ampicillin. Patient stabilized and was transferred to a nonICUmedical ward. Cefepime was continued.

• On day 5, the patient spiked a new fever. Blood cultures were drawn and grew _______. Antibiotics were changed to _______.

• On day 7, the patient’s WBC increased to 30,000, new onset abdominal pain and developed multiple episodes of unformed stools. Diagnosis: _______

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Multidrug-Resistant Organisms (MDROs) Definitions

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MDROs of Epidemiologic SignificanceMDRO

AcronymMicroorganism(s) Antimicrobial Resistance

MRSA Methicillin Resistant Staphylococcus aureus

Oxacillin MIC >4 ug/ml or mecApositive

VISAVRSA

Vancomycin Intermediate S. aureusVancomycin Resistant S. aureus

(I) Vancomycin MIC 4-8 ug/ml(R) Vancomycin MIC >16 ug/ml

VRE Vancomycin Resistant Enterococci Vancomycin MIC >32 ug/ml

CRE Carbapenemase producing Enterobacteriaceae gram negative bacilli

Imipenem or MeropenemMIC >4 ug/ml (CLSI 2011);Positive Modified Hodge test

ESBL Extended spectrum beta-lactamaseenzyme producers (ie. E. coli, K. pneumoniae)

Resistance to 3rd generation cephalosporins (CLSI 2011); ESBL MIC confirmation

Pseudomonas aeruginosa Imipenem or MeropenemMIC >16 ug/ml

Acinetobacter baumanii Imipenem or MeropenemMIC >16 ug/ml

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MDROs Associated with Healthcare-Associated Infections as Reported to

NHSN

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Device-Associated and Surgical Site HAIs Due to MDROs as Reported to CDC/NHSN

Hidron et al. ICHE 2008 (29):996-1011

Total =16% All HAIs associated with MDROs

8% MRSA

4% Vancomycin-resistant Enterococcus faecium

2% Carbapenem-resistant Pseudomonas aeruginosa

1% ESBL cephalosporin resistant Klebsiella pneumoniae

0.5% ESBL cephalosporin resistant Escherichia coli

0.5% Carbapenem resistant Acinetobacter baumannii, K. pneumoniae, K. oxytoca, E. coli

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Device-Associated and Surgical Site HAIs Due to MDROs as Reported to CDC/NHSN

Hidron et al. ICHE 2008 (29):996-1011

Microorganism Device* AssociatedHAIs Resistance

Surgical HAIs Resistance

Staphylococcus aureus 56% MRSA 49% MRSA

Enterococcus species 33% VRE 19.7% VRE

Pseudomonas aeruginosa 31% Fluoroquinolone25% Carbapenems

15.9% Fluoroquinolone11.8% Carbapenems

Escherichia coli 5.5% to 11% ESBL0.9% to 4% Carbapenems

5.3% ESBL2.5% Carbapenems

Klebsiella pneumoniae 21% to 27%ESBL3.6% to10.8% Carbapenems

15.8% ESBL5.2% Carbapenems

Acinetobacter baumaniii 25.6% to 36.8% Carbapenems

30.6% Carbapenems

*Devices include central line catheters, urinary catheters and ventilator associated pneumonia

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Antimicrobial Resistance for Selected Pathogens over Time

ICHE.2008;29;1012.

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http://www.cdc.gov/getsmart/healthcare/index.html

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http://hcupnet.ahrq.gov

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Two Types of Resistance• Natural (Intrinsic)

– Inherent attribute

– E. coli, a gram negative bacilli and Vancomycin, an antibiotic with activity against gram positive bacteria

– Translation: gender or race traits are inherent

• Acquired

– Noninherent attribute usually acquired in genetics, by mutation/evolution or received elements

– An antimicrobial agent once effective is no longer

– Example: Staph aureus resistance to Levofloxacin

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Three Mechanisms of Genetic Adaptation

• Transformation: direct incorporation of free DNA

• Transduction: DNA transfer by a replicating virus

– Bacteriophage

• Conjugation: transfer of genes to a neighboring bacterium in a small circular DNA molecule

– Plasmid

• Bacteria are prolific and some replicate fast

– E. coli doubles every 20 minutes

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Five Mechanisms of Acquired Resistance

• Drug Inactivation – enyzme production like beta-lactamases, carbapenemases

• Cell Wall Changes - impermeable

• Altered Targets – mutational change no longer binding the agent

• Efflux Pumps – expels the antibiotic before reaching the target

• Bypass Targets- mutational change in DNA changing the metabolic energy pathway

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Drug Inactivation

• Beta-lactamases like ESBL

– Engender resistance to penicillin and cephalosporin classes of antibiotics

– Examples: Klebsiella pneumoniae, E. coli

• Carbapenemases

– Engender resistance to imipenem or meropenem

– Examples: Klebsiella pneumoniae, Pseudomonas aeruginosa

• Enzyme break antibiotics down into ineffective molecules before reaching the target

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Drug Inactivation

Enzyme is the bolt cutter => Broken Molecule

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Cell Wall Changes

• Target in cell wall changes and no longer binds the agent

• Examples:

– MRSA and PBP2a and Methicillin/Oxacillin

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Cell Wall Changes

• Barrier to the antibiotic binding or getting into the cell

• Example: Fortress prevents access to the target

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Altered Target

Mutation that no longer binds the antimicrobial agent

Translation: Key no longer works in the door lock

Example: Gentamicinor erythromicinresistance

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Efflux Pump

• Pump in swimming pool or the boat ejects water out when level gets too high

• Example: Fluoroquinolone(levoquin or ciprofloxacin) resistance in E. coli

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Bypass target

• Changed metabolic energy generating pathway

• Example: E. coli & Trimethoprim/Sulfa

• Translation: Change to another path way like a maze

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Antibiotic Misuse Adversely Impacts Patients: Clostridium difficile

• Antibiotic overuse contributes to the growing incidence of C. difficileinfection in healthcare facilities.

• Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile infection (CDI).

– Up to 85% of patients with CDI have antibiotic exposure in the 28 days before infection

• Emergence of the NAP-1/BI or “epidemic” strain of C. difficile has intensified the risks associated with antibiotic exposure.

• Epidemic strain of C difficile is associated with increased risk of morbidity and mortality.

• Epidemic strain is resistant to fluoroquinolone antibiotics, which confers a selective advantage

Chang HT et al. Infect Control Hosp Epidemiol 2007; 28:926–931McDonald LC et al. N Engl J of Med 2005;353:2433-41

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Cumulative Antibiotic Exposures Over Time and the Risk of Clostridium difficile Infection(CDI)

Clin Infect Dis 2011;53:42

• Observed dose dependent increases in the risk of CDI associated with increasing cumulative dose, number of antibiotics, and days of antibiotic exposure.

• Compared to patients who received only 1 antibiotic, the adjusted hazard ratios (HRs) for those who received 2, 3 or 4, or 5 or more antibiotics were 2.5, 3.3, and 9.6, respectively(overlapping).

• The receipt of fluoroquinolones was associated with an increased risk of CDI, while metronidazole was

associated with reduced risk.

Slide: 32MMWR 2011; 60:1171

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Impact of Effective Antibiotic Stewardship Programs on C. difficile Infections

• NAP1/027 strain of C. difficile decreased 60% with total and targeted antibiotic consumption decreased 23% and 54%.

– Valiquette et al. CID 2007 45 (Suppl 2) S112-S121

• C. difficile decreased 41% from 7.2 to 4.8 per 1000 discharges with decreased clindamycin and fluoroquinolone usage

– Muto et al. CID 2007, 45:1266-1273

• C. difficile decreased from 2.2 to 1.4 cases per 1000 discharges with 22% decrease in parenteral broad-spectrum antibiotics

– Carling et al. ICHE 2003:24(9): 699-706

• Other MDRO resistance rates change slowly and can be influenced by other factors in addition to antibiotic use.

http://www.cdc.gov/getsmart/healthcare/support-efforts/asp-int-cdiff.html

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Role of Infection Prevention Science in Antimicrobial Stewardship

• Accelerate progress towards preventing emergence andtransmission of MDROs by applying skills and knowledge ofinfection preventionists and healthcare epidemiologists

• Identify and report trends and outbreaks of epidemiologicallysignificant organisms; educate for understanding about infectionprevention interventions

• Provide support and guidance in approaches to surveillance forsyndromes of interest

• Implement interventions to guide delivery of evidence-basedpractices

• Translate data and infection rates to HCW and leadership

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Antimicrobial Stewardship: Role of the Infection Preventionist

• Implement care bundles and checklists to reduce the riskof getting an infection from use of catheters and devicesor after undergoing a surgical procedure

– Surgical Site infection (SSI)

– Central Line-Associated Bloodstream Infection (CLABSI)

– Catheter Associated Urinary Tract Infection (CAUTI)

– Ventilator-Associated Pneumonia (VAP)

– Clostridium difficile

– Methicillin Resistant Staphylococcus aureus (MRSA)

– Vancomycin-Resistant Enterococcus (VRE)

– Multidrug-resistant Acinetobacter baumannii

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Antimicrobial Stewardship:Infection Preventionist Knowledge and Skill Set

• Proficient in evaluating microbiology culture and susceptibility results.Differentiates between colonization, contamination and pathogens

• Recognizes epidemiologically significant MDROs and atypicalsusceptibility patterns in microbiology results

• Performs surveillance and trending of MDROs for prevalence andnewly emerging MDROs

• Knowledgeable of effective hand hygiene, isolation practices andproducts and procedures for environmental cleaning and disinfectionand evidence based infection prevention practice bundles

• Develops and exhibits leadership promote shared accountability forhighest compliance with practice and multidisciplinary rounding forimproved patient outcomes

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Antimicrobial Stewardship: Role of the Infection Preventionist

• Collaborate with microbiology, pharmacy, medical staff,and administration to plan and implement effectiveinterventions to prevent MDRO in healthcare facilities

• Perform an annual infection prevention risk assessmentfor MDROs

• Meet regulatory requirements of The Joint CommissionNPSG 07.03.01

• Proposed new CMS Conditions of Participation forInfection Prevention assess systems to preventtransmission of MDROs and stewardship activities

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Antimicrobial Stewardship:Microbiology Collaborative

• Specimen Collection Quality• Assure optimal specimens for valid results and optimal antibiotic selection.

• Focus on high frequency specimens known to have volume, adequacy andmicrobial flora contamination challenges

• Specimen preservation and timely collect to plating to preserve the microbial pictureat time of collection

• Gram stain, such as quantified WBC, epithelial cells and bacteria to evaluate quality

• Identification and susceptibility testing for clinically significantpathogens• Correlation of gram stain to culture results

• Quantitation of microbial growth in cfu/ml, few/moderate/many, or 1+, 2+, 3+, 4+

• Identification to genus and species or susceptibility testing is limited on specimensfrom nonsterile sites

• Use of CLSI standards for susceptibility testing and preparation ofcumulative antibiograms

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Antimicrobial Stewardship:Epidemiologic Aspects

• Retain clinically significant pathogens with novel or atypical resistance patterns

• Report to local state Department of Health when indicated

– One time event may qualify as an outbreak (ie first event of CRE)

– Determine occurrences in the region

• Send pathogen for epidemiologic study of resistance to a DOH or recognized research laboratory

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Apply Infection Prevention Knowledge: Community Based Hospital Experiences

• Community based facilities deliver the majority of inpatient care in the US

– Bed size range from

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Examples ofInfection Preventionist Collaboration

• Review all positive blood cultures

– Coagulase negative staphylococci (CoNS) and other skincontaminants are common

– Implement strategies to reduce skin contaminants

• Identify negative cultures and antibiotics beingadministered to review for appropriateness/necessity

• Advocate for appropriate specimen collection, diagnosisand treatment of symptomatic UTI’s

• Endorse computer physician orders; evidence basedorder sets for syndromic diseases/conditions

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Antimicrobial Stewardship: Case Study• 56 year old white female admitted with hypotension, fever, and flank

pain. Her urine showed pyuria and bacteriuria, the peripheral WBC was 16,000. She was admitted to the ICU and empirically started on cefepime.

• On day 2, admission urine and blood grew E. coli sensitive to all tested antibiotics except ampicillin. Patient stabilized and was transferred to a nonICU medical ward. Cefepime was continued. Missed opportunity to de-escalate antimicrobial treatment

• On day 5, the patient spiked a new fever. Blood cultures were drawn and grew Enterococcus faecalis. Antibiotics were changed to Ampicillin/Sulbactam.

• On day 7, the patient’s WBC increased to 30,000, new onset abdominal pain and developed multiple episodes of unformed stools. Diagnosis: Clostridium difficile

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Antimicrobial Stewardship:Infection Prevention Take-Aways

• Evaluate your infection prevention knowledgeand skills. Obtain education and experience tofill gaps.

• Evaluate your annual infection prevention planand incorporate antimicrobial stewardshipactivities and MDRO reporting

• Increase your visibility and leadership ininfection prevention and antimicrobialstewardship

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Resources

• CDC

– http://www.cdc.gov/drugresistance/index.html

– http://www.cdc.gov/getsmart/index.html

– http://wwwn.cdc.gov/dls/master/ams/intro/open.swf

• WHO

– http://www.who.int/mediacentre/factsheets/fs194/en/

• Antimicrobial Stewardship: A collaborative partnership between infection preventionists and health care epidemiologists. AJIC (20) 2012 94-95

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Questions?

Julia.Moody@HCAhealthcare.com

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Save-the-Date: I-APIC HAI Series

Hand Hygiene: Engaging Patients and FamiliesWednesday, June 13, 1pm MT/12pm PTTimothy Landers, CNP, PhD

Summer Bugs: Summer Season Epi TrendsWednesday, July 11, 1pm MT/12pm PT

Central Line InfectionsWednesday, August 8, 1pm MT/12pm PT

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Contact Information

Quality Improvement Organizations

Jennifer PalagiQualis Health, Idaho QIO

jenniferp@qualishealth.org208.383.5944

Tina SchwienQualis Health, Washington QIO

tinas@qualishealth.org206.288.2466

Laurie Murray-SnyderAcumentra Health, Oregon QIOlmurraysnyder@acumentra.org

503.382.3927

Julia MoodyJulia.Moody@HCAhealthcare.com

Intermountain APIChttp://apicintermountain.com/Trish Heath, Education Lead

trishh@slhs.orgGinna Maggard, President

ginna.maggard@hcahealthcare.com

This material was prepared by Qualis Health, the Medicare Quality Improvement Organization for Idaho and Washington, under contract with the Centers for Medicare & Medicaid Services (CMS), an agency of the U.S. Department of Health and Human Services. The contents presented do not necessarily reflect CMS policy. ID/WA-C7-QH-799-05-12

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