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Ronda L. Akins, Pharm.D.

Infectious Diseases Clinical Pharmacy Specialist

Methodist Charlton Medical Center

The “INs” and “OUTs” of Antimicrobial Stewardship: Focusing on the Outpatient at Ambulatory Surgery Centers

Disclosures

• Research support/grants: Allergan, National Institutes of Health

• Advisory Committee: Nabriva Pharmaceuticals

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Objectives

• Describe Antimicrobial Stewardship

• Discuss need and areas for Antimicrobial Stewardship

• Identify CDC core elements for Outpatient Antibiotic Stewardship

• Review National Healthcare Safety Network (NHSN) reporting of Surgical Site Infections (SSI)

• Evaluate various Antimicrobial Stewardship initiatives for improving antibiotic usage/patient outcome

What is Antimicrobial Stewardship?

• Per SHEA: – Coordinated strategies to improve the use of

antimicrobials with the goal of enhancing patient health outcomes, reducing resistance to antibiotics, and decreasing unnecessary costs

• Per APIC – Coordinated program that promotes the appropriate use

of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms

• Per CDC – Designed to ensure patients receive the right antibiotic, at

the right dose, at the right time, and for the right duration

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Why is Antimicrobial Stewardship important?

• Antibiotic resistance

• Impact of antibiotic “mis”-use on patients and

organisms

• Adverse events

• Costs

Antibiotic Resistance

• Historically

– Despite coining the

term “magic bullet”;

Paul Erhlich stated

that “Drug resistance

follows the drug like

a faithful shadow.”

- Paul Erhlich 1854-1915

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Development of Resistance Timeline

Mayo Clin Proc 2012;87:198-208.

http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.

First clinical use

First resistance identified

Penicillin (1942)

Osteomyelitis due to penicillinase-

producing S aureus (1949)

Description of TEM penicillinase

(1966)

Ampicillin (1962)

Cefotaxime (1979)

First clinical

ESBL (SHV-2) (1985)

1940 2019

Imipenem (1985)

Description

of CTX-M (1990)

CRE (1993)

Methicillin (1960)

methicillin-R Staphylococcus

(1961)

Gentamicin (1967)

gentamicin-R Enterococcus

(1979)

Vancomycin (1972)

vancomycin-R Enterococcus

(1988)

Levofloxacin (1996)

levofloxacin-R pneumococcus

(1996)

Linezolid (2000)

linezolid-R Staphylococcus

(2001)

Ceftaroline (2010)

ceftaroline-R Staphylococcus

(2011)

Discovery Void

Lefamulin (2019)

Daptomycin (2003)

Antibiotic Resistance

• Organisms frequently resistance to antibiotics thus concern with empiric coverage

• Associated with high mortality

• MDRO Pathogens

– ESKAPE/ESCAPE

– SPICE/SPACE

– CRE

• https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

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• Unlike other medications, potential for spread of resistant organisms means that the misuse of antibiotics can adversely impact the health of patients who are not even exposed to them (shared resource)

Antimicrob Resist Infect Control. 18 2013;2:31. https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf https://www.cdc.gov/media/releases/2013/p1216-eoy2013.html

Antibiotic Misuse

• Misused in a variety

of ways

– Given when not

needed

– Continued when no

longer necessary

– Wrong dose/drug for

infection

– Broad spectrum for

susceptible

organisms

Impact of antibiotic use/misuse

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Antibiotic Misuse: Prescribing

• Previous data (2013) – up to 50% of antibiotics prescribed were unnecessary/not optimal

• 2017 CDC data – included nursing home usage – 50-75% of residents receive an antibiotic per year

– Up to 75% of antibiotics are prescribed incorrectly

• New data (2018) – released by CDC, August 2019 – Focused on outpatient prescribing

• 5% nationally (2011-2016)

• Estimate annual 47 MILLION antibiotic courses prescribed

• 30% unnecessary, primarily from doctor’s offices / emergency departments

https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf

Antibiotic Misuse: Infection Types

• Most common conditions for antibiotic use – Respiratory infections - 50% antibiotics unnecessary

• Ear, sinus, throat, bronchitis, upper respiratory tract, influenza, asthma, allergy, and pneumonia including viral

– 80% unnecessary bronchitis, fluoroquinolones most common

– Typically given for longer durations 10 days vs 5-7 days

– Skin/soft tissue (cellulitis) • Often treated with broad spectrum agents

– Urinary tract infections • Treatment often for asymptomatic bacteriuria

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Antibiotic Misuse: C. difficile

• Antibiotic exposure is single most important risk factor for Clostridium difficile associated disease (CDAD)

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

Infect Control Hosp Epidemiol. 2007; 28:926-31. JAMA. 2015; 313:398-408.

N Engl J Med. 2015; 372:825-34. Infect Control Hosp Epidemiol. 2009; 30:523-33. Clin Infect Dis. 2008; 46:497-504 https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf

• CDI is the most frequently reported nosocomial pathogen

• Associated with 14,000 - 29,000 deaths annually (US)

• Hospital-acquired, hospital-onset (annually)

– 165,000 cases (9,000 deaths)

• Hospital-acquired, post-discharge (annually)

– 50,000 cases (3,000 deaths)

Antibiotic Misuse: C. difficile

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Incidence of nosocomial C. difficile infection

N Engl J Med. 2015; 372:1539-48.

• Perception that there is (almost) no risk and (almost) all benefit to giving an antibiotic

• In addition to increased potential for developing C. difficile infections, antibiotics can have side effects including allergic reactions (mild to life-threatening)

• Antibiotics account for nearly 1 in 5 (19.3%) of drug-related adverse events

– 79% (~ 4 out of 5) ED visits are due to allergic reactions

Clin Infect Dis. 2008; 47:735. https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

Antibiotic Misuse: Adverse Effects

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• CDC reported 2011-2015 antibiotic-related adverse drug events (abx-ADE)

– 145,000 adult ED visits annually

– Young adults (20-34 years) TWICE likely to visit ED as older adults (>65 years) for abx-ADE

Antibiotic Misuse: Adverse Effects

J Gen Intern Med. 2018; 1060-1068.

• Children – leading cause of ED visits for ADEs

– 70,000 annual visits (age <19 years) for abx-ADEs

Antibiotic Misuse: Adverse Effects

https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf

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• Cost of C. diff infections (annual estimates)

– $1.3 billion excess costs (hosp-acquired, hosp-onset)

– $0.3 billion excess costs (hosp-acquired, post-d/c)

• Cost of antibiotic resistance (annual estimates)

– Up to $20 billion excess cost (direct healthcare)

– Up to $35 billion lost productivity (based on 2008 value)

Antibiotic Misuse: Costs

https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf

• Clinical outcomes better with antimicrobial

management program

0

20

40

60

80

100

Appropriate Cure Failure

AMP

UP

Pe

rce

nt

AMP = Antibiotic Management Program

UP = Usual Practice Am J Med. 2006;119:S53.

Why do we need Antimicrobial Stewardship?

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Clin Infect Dis. 2018. e1-e48. https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf

• Antimicrobial Stewardship – significant reduction in C. difficile rates

– Decreased use of fluoroquinolones

• Reduce use by 30% correlates to 26% decrease in C. diff infections

– Reduce use of other high risk antibiotics

• Clindamycin, cephalosporins (except for surgical prophylaxis)

• 3rd/4th gen cephas, carbapenems

• Other broad spectrum – amox/clav, pip/tazo

– Overall reduction of 10% for antibiotic prescribing in outpatient setting

• Lower C. difficile community-acquired infections by 17%

Why do we need Antimicrobial Stewardship?

Why do we need Antimicrobial Stewardship?

• Estimate saving 37,000 lives from abx resistance over 5 years by improved prescribing/preventing infections

– Prescribing improvement reported in outpatient settings due to ASPs

– ASPs need to be prioritized, including ambulatory settings

• Prevent avoidable antibiotic-related adverse events

• Significant cost savings associated with Antimicrobial Stewardship

– Consistent annual savings $200,000-$400,000

https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf Infect Control Hosp Epidemiol. 2015;36:142-152 Clin Infect Dis, ciz466, https://doi.org/10.1093/cid/ciz466

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Why do we need Antimicrobial Stewardship in ASCs?

• All areas of healthcare should be antimicrobial stewards

• Benefits to patient

• Benefits to society

• Mandates

National Healthcare Safety Network (NHSN) Reporting: 2019 Requirements

• 2015

– Nearly 5,500 Medicare certified ASCs

– Over 16,000 operating rooms

• Replaces SSI event of Patient Safety Component

• SSI surveillance required in Texas

https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf https://www.cdc.gov/nhsn/pdfs/opc/opc-ssi-protocol-current-508.pdf

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NHSN Reporting: 2019 Requirements

• Based on ICD-10 and/or CPT procedure codes

• Surveillance is required for either 30 or 90 days following the procedure

• CDC, 2017 published guidelines for prevention of surgical site infection

– Evidence-based strategies

Surgical Site Infection Criteria Superficial Incisional Deep Incisional Organ/Space

30 days 30 or 90 days 30 or 90 days

Involves only skin and subcutaneous tissue

AND

Involves deep soft tissue AND

Involves any part of body opened/manipulated during

procedure (excluding skin incision, fascia

or muscle layers) AND

purulent drainage, OR isolated organism(s) from

culture, OR superficial incision deliberately opened by surgeon

AND

purulent drainage, OR spontaneously dehisces or

deliberately opened by surgeon

AND

Purulent drainage from drain, OR isolated organism(s) from

culture of fluid/tissue, OR abscess/other infection

involving organ/space, OR dx of organ/space SSI

At least 1 s/sx (local pain/tenderness/swelling,

erythema or heat), OR dx of superficial incisional SSI

At least 1 s/sx (fever, local pain/tenderness), OR

abscess/other infection involving deep incision, OR

dx of deep incisional SSI

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CMS / Joint Commission

• 2016 – CMS final rule for Antimicrobial Stewardship Programs (ASP) in hospitals and critical access hospitals

– Planned to be published June 2019

– Extended until June 2020

• 2017 – TJC mandated ASP in hospitals, critical access hospitals and nursing care centers

• 2020 – TJC mandated ASP in ambulatory health care organizations

– Not applicable to ASCs or office-based surgery program https://www.federalregister.gov/documents/2019/06/11/2019-12216/medicare-and-medicaid-programs-hospital-and-critical-access-hospital-cah-changes-to-promote https://www.jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_Standard.pdf https://www.jointcommission.org/assets/1/18/R3_23_Antimicrobial_Stewardship_AMB_6_14_19_FINAL.pdf

Joint Commission 2020

• Goals

– Identification of responsible individual(s)

• Champion, accountable for ASP activities

– Set at least 1 annual goal to improve prescribing practices

– Use of evidence-based practice guidelines

– Educational resources to all staff/practitioners

– Collect, analyze and report data

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What does this mean for ASCs with Antimicrobial Stewardship?

• No specific guidance/requirements for ASCs

• Utilize hospital and outpatient recommendations to find similar opportunities

• Antimicrobial Stewardship is linked to SSI prevention, surveillance and treatment (when needed)

• Antimicrobial Stewardship Programs in ASCs will improve patient outcome

Historical ASP Guidelines

• Initial guidelines from IDSA 2007 – Geared towards

hospital ASPs

• Subsequent guidelines – IDSA 2016 – Included long-term care

populations

Clin Infect Dis. 2007;44:159-177

Clin Infect Dis. 2016;62:e51-e77

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ASPs

• Who is involved?

– Traditionally ID physician/ID pharmacist

• Not feasible at all facilities - particularly outpatient sites including ASCs

– Administrative support

– Other key stakeholder support

• Minimum

– Physician champion

– Pharmacist

– Infection Prevention

• Or staff member in charge of SSI surveillance

Establishing an ASP

• Identify high-priority conditions for intervention

– Common deviation from best-practice

– Conditions in which antibiotics are overprescribed

– Incorrect antibiotic/dose/duration

• Identify barriers

– Knowledge gap (best practices/guidelines)

– Perception (patient expectations, patient satisfaction)

• Establish standards

– Clear expectations

https://www.cdc.gov/antibiotic-use/community/pdfs/16_268900-A_CoreElementsOutpatient_508.pdf

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Antimicrobial Stewardship Core Elements

• Recommended for outpatient facilities

– NOT developed for ASCs

– No specific references for ASP in ASCs

Antimicrobial Stewardship in an ASC patient

• Pre-operative initiatives – Antiseptic decolonization bundle

• 5 day, 4 body sites vs 2x disinfectant showers

• Studied in elective surgery patients

– Respiratory bundle, post-op PNA • Studied in esophageal cancer patients

• Breathing exercise (deep breathing, breathing exercise devise, respiratory muscle-stretching)

• Oral care (professional oral cleaning, minimum daily teeth/tongue cleaning)

• Nutrition – daily total energy expenditure

• Smoking cessation

Infect Control Hosp Epidemiol. 2018;39:149-1057 Am J Infect Control 2014;42:385-388

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Antimicrobial Stewardship in an ASC patient

• MRSA nasal screening

– Inconclusive evidence of screening and decolonization

– Not universally accepted/utilized

– Not shown to be cost effective

• Vascular day-case procedures

• MRSA risk factors

– Patient with high risk factors

• Nasal screening may have some increased benefit

• Cataract surgery – abx use within previous 30 days

CADTH Technol Overv. 2010; 1(2): e0114 Ann R Coll Surg Engl. 2011;93:44-48 J Cataract Refract Surg 2015;41:387-392

• Urine cultures

– Nonurologic procedures

• No screening nor treatment for asymptomatic bacteriuria (ASB) recommended

– Endourological Procedures

• endoscopic urologic procedures – associated with mucosal trauma: recommend treatment ASB prior

to procedure

– Obtain urine culture and treat targeted organism vs empiric

– If ASB, treat with 1-2 doses (short course) beginning 30-60 minutes before procedure

Antimicrobial Stewardship in an ASC patient

Clin Infect Dis. 2019;68:e83-110

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• Urine screening/cultures – Undergoing placement of artificial urine sphincter or

penile prosthesis implantation • No screening nor treatment for asymptomatic bacteriuria

(ASB) recommended

– Living with (currently in place) implanted urinary devices

• No screening nor treatment for asymptomatic bacteriuria (ASB) recommended

– Urine screening u/a with urine culture should not be routinely performed

Antimicrobial Stewardship in an ASC patient

Clin Infect Dis. 2019;68:e83-110

• Culturing of SSI – Aseptically obtained fluid/tissue

• Extensive cleaning/debridement prior to culture collection

– Superficial swabs not beneficial • Preferred treatment

– Suture removal plus incision/drainage

• Systemic antibiotics – Not routinely warranted

– Possible benefit if SSI > 5cm and systemic s/sx

Clin Infect Dis. 2014;59:e10-e52

Antimicrobial Stewardship in an ASC patient

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Antimicrobial Stewardship in an ASC patient

• Blood cultures – 2 bottles from two different sites (descriptions help)

– If charted at the same time = single set (regardless if drawn correctly)

– Peripheral unless ordered to be drawn from CVC

• Respiratory cultures – If unable to expectorate, sputum induction can be performed

(typically done by RT) • Poor samples often result in normal oral flora

• Limited correlation with lower respiratory pathogens

– Endotracheal aspirates (ETA)

– Broncho-alveolar lavage (BAL) • Most useful but invasive (minimally)

Antimicrobial Stewardship in an ASC patient

• Culture interpretations – Urine

• Requires evaluation of U/A in combination with culture

• U/A: >10 WBC, LE +, nitrite + (high squamous epithelial cells indicates poor collection/contamination)

• Culture typically >100K CFU/mL for infection – May be lower CFU/mL in specific populations (immunocompromised,

catheterized, significant s/sx)

• > 2 organisms per culture suggestive of contamination – Yeast: almost always contaminate

– SSI (wound, fluid, tissue) • S. epidermidis or other coagulase-negative staphylococci likely

contamination

• Multiple organisms (>3, unless aseptically collected) may be in part contamination/colonization

Int J Urol. 2019;26:69-74

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Antimicrobial Stewardship in an ASC patient

• Culture interpretations – Blood

• Single culture (2 bottles) not as useful – Growth from 1 bottle, likely contaminant (depends on organism)

» Especially if from aerobic bottle

– Time to positivity, > 24h tend to be contaminants

• Typical contaminants – Coag-neg staph, Corynebacterium sp. or diphtheroids)

• Never consider as contaminants – GNB, Staphylococcus aureus

– Respiratory • Sputum – often normal flora, not useful

• Other samples – most commonly should be single organisms

• Yeast – considered a contaminant, particularly in upper RTI

Antimicrobial Stewardship in an ASC patient

• Pre-op antibiotic prophylaxis

– Often cefazolin, for coverage of skin organisms

• Limit use only when indicated

– PCN allergies

• Assess reaction (10% reported, < 1% actual)

https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf Jama Surg. 2017;15:784-791

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Antimicrobial Stewardship in an ASC patient

• Post-op antibiotic prophylaxis – Use shortest duration

• Typically 1x pre-op dose sufficient; including clean / clean-contaminated procedures once incision closed in OR

• Ortho / select cardiac procedures: 24-48 hours

– Suboptimal prophylaxis dependent on surgery specialty/facility type

• Genitourinary and Ear/Nose/Throat – Prolonged abx prophylaxis (69 and 18%, respectively)

• Complex hospital outpatient department (highest at 69%) – ASCs 4%; lowest was standard hosp outpatient dept (3%)

Jama Surg. 2017;15:784-791 Antimicrob Resist Infect Control. 2019;8:49

• Treatment of SSI – Systemic antibiotics prescribed

• For longer duration

• For non-first line agents

• Preferred – Incision/drainage

– 1st generation cephalosporin / anti-staphylococcal PCN

– For procedures of axilla, GI tract, perineum, or female genital tract

• Cover for GNB and anaerobes

Antimicrobial Stewardship in an ASC patient

Infect Control Hosp Epidemiol. 2018;39:936-940 Clin Infect Dis. 2014;59:e10-e52

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• Vaccinations

– Influenza vaccinations for HCP no longer mandated

– No clear guidance for surgical patients

• except in splenectomy or asplenic patients – Pneumococcal (initially PCV13), Haemophilus influenzae type

b, influenza

– Meningococcal:

» Quadrivalent (Menveo no interaction with PCV13)

» Meningococcal B (eg, Bexsero)

• Elective surgery – should be performed ~ 2 weeks prior or 2 weeks after

Antimicrobial Stewardship in an ASC patient

Am J Health-Syst Pharm. 2016;73:e220-228

• Evidence-based Interventions

– Shown to decrease prescriptions

• Particularly in select disease states

– Decreased use of macrolides/fluoroquinolones

– Use of Outpatient Core Elements

– Other term utilized for inpatient ASPs

• Audit and feedback (best when prospective audit)

• ?? Implementation in ASCs

Antimicrobial Stewardship in an ASC patient

Infect Control Hosp Epidemiol. 2019. doi.org/10.1017/ice.2019.206

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• Expectations/Changing the Culture

– “Antibiotic Never Events”

• Clinical scenarios where antibiotic use is convincingly inappropriate

• Examples – ABX use for non-susceptible organism

(after sensitivities known)

– ABX for viral upper respiratory infections

– Post-surgical prophylaxis exceeds national guidelines

– ABX for asymptomatic bacteriuria

Antimicrobial Stewardship in an ASC patient

Infect Control Hosp Epidemiol. 2019;40:206-207

What can nurses do?

• Accurate allergy history – Reaction important for cross-sensitivity

• Culture collection – Prior to antibiotics is preferred

• Antibiotic administration – Timing

• Before procedure (recommended ~ 1hr prior) • After - look at durations

• Adverse events – Document reactions

• Patient education – Discharge instructions, ensure patient has clear

understanding particularly when abx are involved

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What can Infection Prevention do?

• Preventing spread of infection

– Hand hygiene

– Isolation precautions

– Disinfection of equipment and environment

• Tracking

– Hospital-acquired infections (HAI)

– SSIs

– Reportable conditions/organisms

What can the prescriber do? • Treatment/prophylaxis

– Only if appropriate

– Shortest duration

• Review cultures – Modify therapy per sensitivities/need to continue

• Documentation – Specify indication/duration, plan for de-escalation, po

conversion

• Remember: – Broader spectrum is NOT always better NOR do they “kill”

faster

– More is NOT always better (single abx often effective)

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Summary

• Antimicrobial Stewardship crucial to be performed for all patients at all healthcare facilities – BE VISIBLE, SPREAD THE

KNOWLEDGE

• Impact on resistance is significant

• Requires investment, persistence and feedback

• Benefits patients and society

Questions

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Resources • https://www.cdc.gov/nhsn/ambulatory-surgery/index.html

• https://www.cdc.gov/antibiotic-use/community/pdfs/16_268900-A_CoreElementsOutpatient_508.pdf

• https://www.jointcommission.org/assets/1/6/New_Antimicrobial_Stewardship_Standard.pdf

• https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report-2018-508.pdf

• https://www.cdc.gov/antibiotic-use/stewardship-report/pdf/stewardship-report.pdf

• https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

• https://jamanetwork.com/journals/jamasurgery/fullarticle/2623725

• https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf

• https://www.cdc.gov/nhsn/pdfs/opc/opc-ssi-protocol-current-508.pdf

• https://www.idsociety.org/practice-guideline/skin-and-soft-tissue-infections/

• https://www.idsociety.org/practice-guideline/implementing-an-ASP/

• https://academic.oup.com/cid/article/44/2/159/328413

• https://academic.oup.com/cid/article/68/10/e83/5407612

• https://academic.oup.com/cid/article/66/7/e1/4855916