Antimicrobial Stewardship: Response to a Global Crisis Carla - - PowerPoint PPT Presentation

Antimicrobial Stewardship: Response to a Global Crisis

Carla Walraven, PharmD, BCPS-AQ ID University of New Mexico Hospital Antimicrobial Stewardship Program

Pharmacist Objectives

• Explain the implications of antimicrobial

resistance

• Prepare for the new regulatory standards for

Antimicrobial Stewardship Programs (ASPs)

• Outline strategies employed by ASPs to

improve outcomes

• Identify opportunities to apply Antimicrobial

Stewardship concepts

Pharmacy Technician Objectives

• Identify ways in which antibiotics are misused
• Explain the implications of antimicrobial

resistance

• Recognize the core elements of Antimicrobial

Stewardship Programs

Audience Poll

• A 19 YOM is brought to your ED after an

accident cleaning his homemade shotgun, resulting in a penetrating eye socket injury with a metal pipe.

– How many would recommend antibiotics? – Which antibiotics would you use? (What pathogens are you concerned about?)

The Curious Case of Phineas Gage

(July 9, 1823 – May 21, 1860)

• In 1848, Phineas Gage was struck by a tamping iron while

working on the railroad

• He survived the accident, but was not the same afterwards
• Died at the age of 36, after a series of seizures

http://www.smithsonianmag.com/history/phineas-gage-neurosciences-most-famous-patient-11390067/?no-ist

Fast Forward to 2016…

• 61 YOM newly diagnosed

AML

• Antibiotic exposure:

– Cetriaxone, clindamycin x 14 days (shin injury) – Vancomycin (cellulitis) – Augmentin and ciprofloxain (prophylaxis)

• Febrile neutropenia 16

days after admission

– Blood cultures grew an Extended spectrum β- lactamase (ESBL) E. coli

ESBL E. coli MIC

Amikacin 16 Susceptible Aztreonam > 16 Resistant Ciprofloxacin > 2 Resistant Ceftriaxone > 32 Resistant Cefazolin > 16 Resistant Ertapenem > 1 Resistant Gentamicin > 8 Resistant Meropenem 4 Resistant Ampicillin/sulbac > 16/8 Resistant Piperacillin/tazo > 64/4 Resistant Sulfameth/trimeth > 2/38 Resistant

https://www.cdc.gov/drugresistance/about.html

Going Back to a Pre-Antibiotic Era?

• Antibiotic resistance has

been called one of the world’s most pressing public health concerns

• Antibiotic resistance is

associated with increased lengths of hospital stay, increased costs, and increased mortality

“30-50% of antimicrobial use is either unnecessary or inappropriate.”

0% 5% 10% 15% 20% 25% 30% 35% % of Patients with Unnecessary DOT

Most Common Reasons for Unnecessary Therapy

Noninfectious Syndrome Tx of Colonization or Contamination Duration of tx Longer than Necessary Redundant Abx Coverage

Reimann HA, D’Ambola J. JAMA. 1968;205(7):537. Hecker MT, et al. Arch Intern Med. 2003;163:972-78.

N = 576 DOT

Antibiotic Misuse

• Antibiotics are given when they are not needed
• Antibiotics are continued longer than necessary
• Antibiotics are given at the wrong dose
• Broad spectrum antibiotics are used to treat

highly susceptible bacteria

• The wrong antibiotic is used to treat an infection

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

Antibiotic Prescribing Trends in US Hospitals, 2006 - 2012

2006-2012

Baggs J, et al. JAMA Intern Med. doi:10.1001/jamainternmed.2016.5651

Piperacillin/tazobactam – Resistant Pseudomonas aeruginosa

http://gis.cdc.gov/grasp/PSA/MapView.html, Accessed Aug 2016.

National Action Plan for Combating Antibiotic-Resistant Bacteria

• 5 Goals

– Slow the emergence and spread of resistant bacteria

• Includes the implementation of antimicrobial stewardship

programs

– Strengthen national surveillance efforts of resistant bacteria – Advance development and use of rapid diagnostic tests – Accelerate research and development of new antibiotics, therapeutics, and vaccines – Improve international collaborations regarding antimicrobial use and misuse

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf, Accessed Aug 2016.

What is Antimicrobial Stewardship?

Coordinated program that promotes the appropriate use

• f antimicrobials, improves patient outcomes, reduces

microbial resistance, and decreases the spread of infections caused by multi-drug resistant organisms.

Barlam TF, et al. Clin Infect Dis. 2016; e1-e27. http://www.apic.org/Professional-Practice/Practice-Resources/Antimicrobial-Stewardship

CDC’s Core Elements for ASPs

 Obtain leadership commitment

• Includes dedicating necessary human, financial and

information technology resources

 Appoint a single leader responsible for program

• utcomes

 Appoint a single pharmacist leader responsible for working to improve antibiotic use  Obtain support from key stakeholder

• Infection control and prevention
• Information technology
• Quality improvement
• Clinicians

http://www.ahaphysicianforum.org/resources/appropriate-use/antimicrobial/content%20files%20pdf/CDC%20checklist.pdf

CDC’s Core Elements for ASPs (cont.)

 Implement policies and interventions to improve antibiotic use  Evaluate ongoing treatment need after an initial treatment period

• E.g. “Antibiotic timeout” after 48 hours

 Monitor antibiotic prescribing and resistance patterns  Regularly report information on antibiotic use and resistance to doctors, nurses, and relevant staff  Educate clinicians about resistance and optimal prescribing

CMS §482.42(b): Antibiotic Stewardship Program Organization and Policies

• Effective January 1, 2017
• Demonstrate coordination among all components
• f the hospital responsible for antibiotic use and

factors that lead to antimicrobial resistance

• Document the evidence-based use of antibiotics

in all departments and services of the hospital

• Demonstrate improvements, including sustained

improvements in proper antibiotic use

https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-13925.pdf

TJC’s New Antimicrobial Stewardship Standard

Effective January 1, 2017 Download available at: https://www.jointcommission.org /standards_information/prepublic ation_standards.aspx

Antimicrobial Stewardship Team

ASP Physician Pharmacist Infection Control Infectious Diseases Pharmacy Informatics Microbiology Hospital Admin

ASP Activities

• Patient Centered

– Prospective audit and review – Formulary management – Identify patients who may benefit from ID consult

• Institutional

– Antibiograms – Clinical pathways – Dose optimization

Impact of Interventions

ASP Interventions

Patient Institution

National Global

Goal: Decrease or slow antimicrobial resistance

ASP Core Strategies

Core Strategies Advantages Disadvantages

Prospective audit with direct intervention and feedback

• May reduce inappropriate

antimicrobial use

• Educate to modify future

prescribing

• Allows prescribers to

maintain autonomy

• Difficulty identifying

patients with inappropriate therapy and communicating with prescribers Formulary restriction and preauthorization requirements

• May result in immediate

and substantial reduction in antimicrobial use and costs

• May increase staffing

requirements

• May delay order

implementation with potential adverse patient

• utcomes
• May increase use of and

resistance to alternative antimicrobial agents

• Perceived loss of prescriber

autonomy

Dellit et al. Clin Infect Dis. 2007;44:159-77. Drew et al. Pharmacotherapy. 2009;29:593-607.

ASP Supplemental Strategies

Dellit et al. Clin Infect Dis. 2007;44:159-77. Drew et al. Pharmacotherapy. 2009;29:593-607.

Supplemental Elements Advantages Disadvantages

Education

• May influence prescribing

behavior

• Marginally effective when

used without active intervention Evidence based guidelines and clinical pathways

• May improve antimicrobial

use and practice variations

• Poor adherence

Streamlining or de-escalation therapy

• Reduces antimicrobial

exposure, selection of resistant pathogens, and health care costs

• Prescriber reluctance to de-

escalate when cultures are negative and clinical improvement observed Dose optimization

• Tailors therapy to patient

characteristics, pathogen, and PK/PD of antimicrobial

• Nursing concerns regarding

incompatibilities and administration IV to PO conversion

• May decrease length of

hospital stay and costs

• May reduce complications

associated with IV access

• Difficulty identifying patients

in whom conversion is appropriate

PATIENT CASE

Implementing Antimicrobial Stewardship

Healthcare-Associated Pneumonia

• 49 YOF with history of severe COPD is admitted

from a skilled nursing facility for respiratory distress and acute disorientation (per family)

– Increased cough with sputum production over the past 24h – No fevers or chills

• Diagnosis: Acute hypoxic respiratory failure due

to healthcare-associated pneumonia (HCAP)/aspiration with sepsis

HCAP

Physical Exam

• General: Obese female,

respiratory distress, alert/responsive

• ENT: no nasal discharge
• Respiratory: Bilateral rhonchi,

crackles in right upper & middle lobes, intermittent expiratory wheeze Vitals & Labs

• T 37.6˚C, HR 123, BP

151/73, RR 21, O2 91%

• WBC 24.4
• Lactate 1.8
• No medication allergies

Patient is started empirically on vancomycin and piperacillin/tazobactam

Antimicrobial Timeout

• As soon as possible, or within 48 hours:
• 1. Does the patient have an infection that will

respond to antibiotics?

• 2. If so, is the patient on the right antibiotic(s),

dose, and route of administration?

• 3. Can a more targeted antibiotic be used to treat

the infection (de-escalate)?

• 4. How long should the patient receive the

antibiotic(s)?

http://pqc-usa.org/timeout/

Incorporating Culture Results

True Bacteremias N TTP at 24 h TTP at 48 h TTP at 72 h

Gram positives MRSA MSSA

• S. pneumonia
• E. faecalis
• E. faecium

52 41 6 30 19 85% 93% 100% 87% 89% 98% 98% 100% 97% 100% 98% 100% 100% 100% 100% Gram negatives

• E. coli

Klebsiella spp. Pseudomonas spp. Acinetobacter spp. 161 62 30 22 8 88% 97% 97% 82% 100% 98% 100% 100% 100% 100% 99% 100% 100% 100% 100% Anaerobic 23 39% 74% 91% All Contaminants 210 48% 85% 92%

Pardo J, et al. Ann Pharmacother. 2014; 48(1):33-40.

TTP = Time to Positivity

Impact of Prior Antibiotics on Cultures

Positive by 48 hours Positive by 72 hours Off Antibiotics On Antibiotics P-value Off Antibiotics On Antibiotics P-value Gram positives (n = 232) 183 / 186 (98%) 44 / 46 (96%) 0.258 183 / 186 (98%) 46 / 46 (100%) >0.99 Gram negatives (n = 161) 137 / 139 (99%) 20 / 22 (91%) 0.09 138 / 139 (99%) 21 / 22 (95%) 0.255 Anaerobes (n = 23) 15 / 19 (79%) 2 / 4 (50%) 0.270 18 / 19 (95%) 3 / 4 (75%) 0.324 All episodes (n = 416) 335 / 344 (97%) 66 / 72 (92%) 0.03 339 / 344 (99%) 70 / 72 (97%) 0.348

Pardo J, et al. Ann Pharmacother. 2014; 48(1):33-40.

Using Surveillance Cultures

• Association between MRSA nasal swab results

and the presence of MRSA pneumonia

– Nasal colonization is a risk factor for infection – Results within a few hours

MRSA PCR assay N = 435 Sensitivity 88% Specificity 90.1% Positive predictive value 35.4% Negative predictive value 99.2%

Dangerfield B, et al. Antimicrob Agents Chemother. 2014; 58(2):859-64.

Utility of Negative Culture Results

• Early antibiotic discontinuation with negative cultures

Early Discontinuation (n = 40) Late Discontinuation (n = 49) P-value Hospital mortality 10 (25%) 15 (30.6%) 0.642 Clinical Pulmonary Infection Score, median 4 4 0.523 Signs/symptoms Abnormal temp Abnormal WBC Sputum purulence 15 (48.4%) 20 (69%) 24 (66.7%) 21 (61.8%) 23 (65.7%) 34 (80.9%) 0.324 1.00 0.196 Superinfection Bacteremia Respiratory infection MDR Superinfection 9 (22.5%) 1 (2.5%) 4 (10%) 3 (7.5%) 18 (42.9%) 3 (7.1%) 12 (28.6%) 15 (35.7%) 0.008 0.616 0.036 0.003

Raman K, et al. Crit Care Med. 2013; 41(7): 1656-63.

Comparison of 8 vs. 15 Days 60-Day VAP Mortality

How Long to Treat?

• Antibiotic duration for VAP

– Primary outcome: death, 28 days after VAP onset

• Prospective, randomized

double-blind, clinical trial

– 51 French ICUs – May 1999 to June 2002 – Adults meeting clinical criteria for VAP

Chastre J, et al. JAMA. 2003; 290(19):2588-2598.

Stewardship Recommendations

Clinical Status & Culture Results

• T 36.7 ˚C, RR 18, HR 98, BP

128/62, O2 95% on 3L NC

• WBC 18.7
• MRSA nares negative
• Urine S. pneumoniae

antigen negative

• Blood cultures x 2 sets: no

growth Now What?

• MRSA nares has > 99%

negative predictive value

– Discontinue vancomycin

• Do we need Pseudomonal

coverage?

– Consider de-escalating piperacillin/tazobactam – IV to PO if possible

• Duration: 7 days

DO YOU REALLY NEED DEDICATED STEWARDSHIP PERSONNEL?

Lessons Learned from one ASP

• University of Maryland Medical Center

(UMMC)

• 725 bed medical facility in Baltimore, MD

– 175 ICU beds – Active cancer, transplant, and trauma centers

• Stewardship program started in 2001 to help

contain increasing drug costs

– Goal: To save 10-20% the cost of antibiotics over a 3-year period

Standiford HC, et al. Infect Control Hosp Epidemiol. 2012: 33(4):338-45.

ASP Duties

• ID Physician, 0.5 FTE
• ID Pharmacist, 0.8 FTE
• Data Analyst, 0.05 FTE

Duties

• Identify ineffective or excessive

antibiotic coverage

• Ensure adherence to hospital

policies and guidelines

• Identify opportunities for IV to

PO conversions

• Suggest ID consult in complex

cases

• Review restricted antibiotics
• Review patients not serviced by

the ID physicians (e.g. the trauma center)

UMMC ASP Program

Standiford HC, et al., Infect Control Hosp Epidemiol. 2012, 33(4):338-45.

Disbanded in 2008

Use resources to increase the number of ID physicians

Before, During and After UMMC ASP

Antimicrobial Costs by Quarter, FY 98 – FY 10

Post-ASP Conclusions

• Despite unchanged quality markers,

antimicrobial costs continued to increase (by 41.2%) in the 2 years after the ASP ended

“…suggesting that more and more costly antibiotics were being used without an increase in benefit.”

Average Cost Savings: $500K per year (2001 – 2008) Average Cost Increase: $1 million per year (2009 – 2010)

Differing ASP Models

Dedicated ASP Model

• 312 beds
• Average daily census: 230
• ID pharmacist rounds daily with

the ID team

• 2011 to 2012

Geographic ASP Model

• 137 beds
• Average daily census: 103
• 4 ward PharmDs round daily with

their respective teams

• 2010 to 2011
• Evaluation of two Department of Veterans Affairs Hospitals
• Similar range of services available
• ID consultation available at all times
• Inpatient rehabilitation facilities
• Antimicrobial stewardship efforts at both with active ID

physician participation

Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.

Primary Endpoint

• Composite of compliance with the all of the

following:

– Therapy modification within 24 hours of laboratory data – Discontinuation of therapy when determined to be non-bacterial – Intravenous to oral (IV to PO) conversion when appropriate

• Policies and guidelines based on the Department
• f Veterans Affairs (VA) National Formulary and

VA Pharmacy Benefits Management group

Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.

Antimicrobial Stewardship Activities

Dedicated ASP Geographic ASP P-value Discontinuation of therapy when not bacterial 37/48 (77.1%) 11/33 (33.3%) 0.0002 Therapy modification based on laboratory data 143/190 (75.2%) 51/100 (51%) < 0.0001 Therapy modification within 24 hours of laboratory data 124/143 (86.7%) 37/51 (72.6%) 0.029 IV to PO conversion when appropriate 97/120 (80.8%) 41/67 (61.2%) 0.0052 All of the above streamlining activities 165/182 (90.7%) 47/95 (49.5%) < 0.0001

Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.

Conclusions

• An ASP with a dedicated pharmacist was

associated with better adherence to stewardship activities

• There was a higher rate of adherence to

stewardship activities even when ID was consulted

– Benefit of having both ID consult and an ASP with dedicated personnel

Bessesen MT, et al. Hosp Pharm. 2015; 50(6):477-483.

HOW CAN ONE PHARMACIST OVERSEE ALL ANTIMICROBIAL USE?

Using Clinical Pathways

• Concise summary of

national guidelines

• Includes local

susceptibility recommendations

• Contains key

educational points

• Goal is to capture 80%
• f patients with a

particular disease state

“…the strength of the Pack is the Wolf, and the strength of the Wolf is the Pack.”

Mean ± SD Expenditure Cost Savings†

Baseline Intervention Daily Yearly Ceftazidime $115 ± $47 $80 ± $27 $35 $12,775 Imipenem $299 ± $84 $232 ± $112 $67 $24,455 Levofloxacin $497 ± $35 $448 ± $31 $49 $17,885 Piperacillin/tazo $2,110 ± $134 $2,037 ± $11 $73 $26,645 Vancomycin $1,221 ± $79 $1,008 ± $9 $213 $77,745

• Grady Memorial Hospital in Atlanta, GA
• Prospective audit with intervention and feedback of non-ICU

patients

• Mortality, LOS, and re-admissions were similar for both periods
• Emergence of resistance decreased from 9.5% to 5% (P = 0.06)

DiazGranados CA, et al. Am J Health-Syst Pharm. 2011;68:1691-2.

†Extrapolated savings based on cost data during intervention period

WE DON’T HAVE ANY INFECTIOUS DISEASE TRAINED SPECIALISTS

Stewardship Training Programs

Making a Difference in Infectious Diseases (MAD-ID)

• Basic program
• Advanced program
• 19 contact hours (1.9 CEUs)

each

• http://mad-

id.org/antimicrobial- stewardship-programs/

Society of Infectious Disease Pharmacists (SIDP)

• Partnered with ProCE

– info@proce.com

• Offers up to 43 contact

hours (4.3 CEUs)

• http://www.sidp.org/Stewa

rdship-Program

Additional Resources

• STEWARDSHIP-EDUCATION.org

– Collaborative project between SHEA, IDSA, PIDS, NFID, MAD-ID, SIDP, and ASHP

• APIC’s Stewardship Toolkit

– http://www.apic.org/Professional-Practice/Practice- Resources/Antimicrobial-Stewardship

• CDC’s Get Smart Campaign

– http://www.cdc.gov/getsmart/ – Checklist for Core Elements of Hospital Antibiotic Stewardship Programs

Summary

• Antibiotics are a communal but scarce

resource

• Reducing unnecessary antibiotic use can

decrease antibiotic resistance

• Starting in 2017, TJC and CMS will mandate all

hospitals have ASPs

• Successful ASPs impact the patient, the

institution, and hopefully beyond

Questions?

Contact Info:

Carla Walraven, PharmD, BCPS-AQ ID University of New Mexico Hospital 2211 Lomas Blvd NE Pharmacy Department, 4ACC North Albuquerque, NM 87106 (505) 272-4669 cwalraven@salud.unm.edu