Antibiotic Stewardship – What is It? · UND School of Medicine & Health Sciences Altru Family...

Antibiotic Stewardship –

What is It?

Richard Clarens, PharmD

UND School of Medicine & Health Sciences

Altru Family Medicine Residency

NDSU College of Pharmacy, Nursing, & Allied

Sciences

OBJECTIVES

• Discuss factors that have increased antimicrobial

resistance.

• Define and identify the principles of antibiotic

stewardship.

• Identify strategies to incorporate antimicrobial

stewardship to improve antibiotic use.

ANTIBIOTIC PRESCRIBING

• In 2013 ~269M outpatient antibiotic RxsCDC. Outpatient antibiotic prescriptions – US, 2013. http://

www.cdc.gov/getsmart/community/pdfs/annual-reportsummary_2013.pdf

• In 2009 ~$10.7B on antibiotics

– Outpatient $6.5B

– Inpatient $3.6B

– LTCF $526.7MMMWR 15;64:871-3. Aug 21, 2015

OUTPATIENT ANTIBIOTIC USE

• Up to 80% of antibiotics Rx’d in primary carePharm J 10/13/2011. http://www.pharmaceutical-journal.com/news-and-

analysis/news/pharmacists-have-a-critical-role-in-the-conservation-of-effective-

antibiotics/11086917.article

• ~20% peds & 10% adult visits receive abx RxPediatrics 11;128:1053-61 J Antimicrob Chemother 14;69:234-40

• ~30% of antibiotics unnecessaryJAMA. 2016;315:1864-1873

MISUSE OF ANTIBIOTICS

• Estimated $34.1 B/y in avoidable inpatient costs

• $1 B/y spent on ~31 M inappropriate Rx

– Typically for viral infections

– Bronchitis 11 M

– Sinusits 9 M

– Pharyngitis 6 M

– Otitis media 3 M

– URI 2 MIMS Institute for Healthcare Informatics. Using Medicines More Responsibly. 6/19/13.

http://www.imshealth.com/en/about-us/news/ims-health-study-identifies-$200-billion-annual-

opportunity-from-using-medicines-more-responsibly

ANTIBIOTIC PRESCRIBING 2011

• Antibiotic agent Rx’s in millions

– Azithromycin 54.1

• 10th most Rx’d drug in 2011

• 16th in 2014

– Amoxicillin 52.9

• 11th most Rx’d drug in 2011 and 2014

– Amoxicillin-clavulanate 21.2

– Ciprofloxacin 20.9

– Cephalexin 20.0Clin Infect Dis 15;60:1308-16

http://www.pharmacytimes.com/publications/issue/2015/july2015/top-drugs-of-2014

ANTIBIOTIC USE

• “perceived low toxicity, antibiotics are seen as

ultrasafe “miracle drugs” by physicians and

patients alike.”

• “providers dispense antibiotics, often

reflexively”J Ped ID Soc 15;4:e136-e8

ANTIBIOTIC USE• Often overused and used inappropriately

– Up to 50%

• Selection, dosing, duration, unnecessary for condition

– > 25% adult Rxs usually not indicated

• Inappropriate antibiotic use:

– Leads to adverse drug effects (ADE) (eg,

hypersensitivity, C. difficile) and mortality

– Increases health care cost (eg, ED visits, Rx)

– Promotes antibiotic resistanceArch Intern Med 10;170:1314-6 J Antimicrob Chemother. 2014;69(1):234-40

CDC. Grand Rounds: Getting Smart About Antibiotics. MMWR 15;64:871-3

JAMA 16;315:562-70 Editorial. Ann Intern Med 12;157:211-2

Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7

ED visits for

ADE, %

ED visits resulting in

hospitalization, %

Anticoagulants 17.6 48.8

Antibiotics 16.1 7.1

DM agents 13.3 38.5

Opioid Analgesics 6.8 24.6

RAAS inhib 3.5 31.9

Antineoplastics 3 59.7

NSAIDs 2.8 12.6

Antihistamines 1.3 11.9

Cough/Cold 1.3 10.9JAMA. 2016;316(20):2115-2125

US ED Visits for ADEs by Drug Class, 2013-2014

US ED Visits for Adverse Drug Events,

2013-2014

• Per-prescription risk is greater than benefits for

many outpatient URTIs

• Rates of antibiotic use is highest for children

– Higher rate of ED visits for ADEs vs other drugs

• Reducing inappropriate antibiotic use by using

various interventions

– May reduce the risk of ADEs and resistanceCDC. Get smart: know when antibiotics work. http://www.cdc.gov/getsmart/community/improving-

prescribing/interventions/index.html.

JAMA. 2016;316(20):2115-2125

INFECTIONS DUE TO

RESISTANT PATHOGENS

• ~ 2 M/y infected with abx-resistant bacteria

• ~ 23,000/y die as a direct result and more from

complications from other conditions

• ~ 8 million additional hospital days/y

• Cost of resistance ~ $20B/y in excess costs

– ~$35B in lost productivityCDC. www.cdc.gov/media/releases/2011/f0407_antimicrobialresistance.pdf.

Pew Health.

http://www.pewhealth.org/uploadedFiles/PHG/Supporting_Items/FactSheet_Threat.pdf

CDC. www.cdc.gov/drugresistance/DiseasesConnectedAR.html

MMWR 15;64:871-3. Aug 21, 2015

CDC’s ANTIBIOTIC-RESISTANT

THREATS IN US – 2013 (Partial List)

• Urgent threat level

pathogens

– C. diff

– N. gonorrhoeae

• Serious threat level

pathogens

– Extended Spectrum β-

Lactamase (ESBL) bacteria

– P. aeruginosa

– MRSA

– Vancomycin-Resistant

Enterococcus (VRE)

– Drug-Resistant S.

pneumoniae

• Of concern threat level

pathogens

– Vanc-Resistant S. aureas

– Erythro-Resistant GABHS

– Clindamycin-Resistant

GBS

White House. National action plan for combating antibiotic-resistant bacteria. 3/15

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating

_antibotic-resistant_bacteria.pdf

C. diff Infection (CDI) in Hospitals

• CDI discharge diagnosis 2x increase 2000-09

• Increases length of stay by 2.8-5.5 d

• Cost for inpatient 1-4.9 B/y

• 5-10% mortality – ~14,000-20,000 deaths/y

• Every antibiotic has been associated with CDI

– FQ commonly implicated due to number of Rx

– Strategies to prevent CDI include “antimicrobial

restriction and stewardship”Infection Control & Hospital Epidemiology 14;35:628-45 NEJM 15;372:1539-48 CDC

ACUTE BACTERIAL SINUSITIS

THERAPY

• ß-lactams recommended as empiric therapy

rather than a FQ

• Macrolides are not recommended for empiric

therapy due to high S. pneumoniae resistance

(~30%)

• TMP/SMX is not recommended for empiric

therapy due to high S. pneumoniae and H. flu

resistance (~30-40%)Bacterial Rhinosinusitis Guideline. 2012. http://www.idsociety.org/Organ_System

ALTRU ANTIBIOGRAM 2015

History E. Coli susceptibility

Ciprofloxacin: 2007 96%; 2010 93%; 2011 90%, 2013 88%

TMP/SMX : 2007 90%; 2010 87%; 2011 84%, 2013 84%

EMPIRICAL TREATMENT OF ACUTE

UNCOMPLICATED PYELONEPHRITIS

• Outpatient

– Cipro for 7 d or Levofloxacin for 5 d

• 1st-line empiric therapy (2nd-line for cystitis)

• If local resistance is < 10%

• If >10% resistance give initial dose ceftriaxone or

aminoglycoside

– TMP/SMX for 14 d if pathogen susceptible

• If empiric give initial dose ceftriaxone or

aminoglycosideIDSA Guidelines. Clin Infect Dis 11;51:e103-e120. NEJM 12;366:1028-37.

Ann Intern Med 12;ITC3 3/6/12 JAMA 14;311:844-54 Dis-a-Mon 15;61:45-59

CASE

• 81 y/o male with fever to 38.2 C, chills, dysuria

– h/o BPH and past UTIs

• U/A +

• Ciprofloxacin 400 mg IV 2xd

• UC E. coli

– R – Ampicillin; Ciprofloxacin; TMP/SMX

– S – Amp/sulbactam; Ceftriaxone; Gentamicin;

Nitrofurantoin

• 7 mon prior – E coli

– R – Amp, Cipro I – Amp/sulbactam

– S – Cefazolin, Ceftriaxone, Gent, Nitrofurantoin, TMP/SMX,


– R – Amp, Cipro, Amp/sulbactam, TMP/SMX

– S – Cefazolin, Ceftriaxone, Gent, Nitrofurantoin, Tobra


– R – Amp, Cipro, Amp/sulbactam, TMP/SMX, Nitrofurantoin

– S – Cefazolin, Ceftriaxone, Gent, Tobra

• 1 mon prior – Citrobacter, Enterococcus, Pseudo

– Not treated

• Symptomatic – UC grew C. albicans

– Empiric Ceftriaxone – Switched to Fluconazole

Antibiotic Judo. Working Gently With

Prescriber Psychology to Overcome

Inappropriate Use

• “Every individual’s use of antibiotics contributes

to loss of their efficacy over time for everyone

else.

• “… person takes an antibiotic for an infection

that is probably viral, with a small possibility

that it is bacterial, there may be a small potential

benefit to that person, balanced against a slight

collective harm to society.”Spellberg B. Commentary. JAMA IM. online Jan 27. 2014

Antibiotic Judo. Working Gently With

Prescriber Psychology to Overcome

Inappropriate Use

• “When this happens frequently, the collective

potential benefit to the users remains small, but

harm to society grows.

• “When it occurs hundreds of millions of times

per year … the aggregate harm to society is

catastrophic”

• Need for antibiotic stewardship programsSpellberg B. Commentary. JAMA IM. online Jan 27. 2014

CDC Grand Rounds: Getting Smart

About Antibiotics

• Acute RTIs – most inappropriate abx use

– No abx recommended for acute bronchitis

• 71% received abx

– Pharyngitis in adults usually don’t require abx

• 5-10% due to GABHS – ~60% received abx

• Selection of agent may be inappropriate

– Broad-spectrum (eg, 2nd- or 3rd-line abx) often used

– 2nd- 3rd- generation ceph, FQ usually not 1st-line

– 2007-09 74% of Rx for RTIs were broad-spectrumMMWR 15;64:871-3. Aug 21, 2015 Gerber JS. Editorial JAMA 16;315:558-9

“The CDC recommends that all acute care

hospitals implement an antibiotic stewardship

program”http://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html

“Despite published clinical guidelines and

decades of efforts to change prescribing patterns,

antibiotic overuse persists”JAMA 16;315:562-70

ANTIBIOTIC STEWARDSHIP

DEFINITION

• Coordinated interventions to:

– Measure antibiotic prescribing

– Improve prescribing by clinicians and use by

patients – used only when needed

– Minimize misdiagnoses or delayed diagnoses

leading to underuse of antibiotics

– Promote selection of optimal antibiotic and the right

dose, duration, and routeCDC. Antibiotic resistance threats in the United States, 2013.

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

Implementing an Antibiotic Stewardship Program: Guidelines by the IDSA and the SHEA. Clin

Infect Dis 16;62:e51-77. http://dx.doi.org/10.1093/cid/ciw217

ANTIBIOTIC STEWARDSHIP

• Inpatient, outpatient, and long-term care settings

• Is practiced at the

– Level of the patient

– Level of a health-care facility or system, or network

• Should be a core function of healthcare

providers

• Utilizes expertise and experience of clinical

pharmacists, microbiologists, infection control

practitioners and information technologistsGet Smart About Antibiotics. Introduction to Prudent Antibiotic Use. Antibiotic Stewardship

Curriculum. Developed by Luther VP, Ohl CA.

EXAMPLES OF ANTIBIOTIC

STEWARDSHIP OBJECTIVES

• Empirical therapy according to local or

national guidelines

• Blood and site of infection cultures before abx

• De-escalation of therapy

– Change to narrow spectrum antibiotic or stop as soon

as culture and susceptibility results available

• Adjustment of therapy to renal functionLancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7



• Switch from IV to oral therapy

– After 48-72 h if stable, oral intake and GI absorption

adequate

– Adequate serum concentrations with oral

• Documented antibiotic plan

– Indication, drug name and dose, and administration

route and interval

– Included in note at start of treatment

• Therapeutic drug monitoringLancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7



• Discontinuation of empirical treatment based on

lack of clinical or microbiological evidence of

infection

• Local antibiotic guide present in the hospital

and assessed for update every 3 years

• Local antibiotic guide in agreement with

national antibiotic guidelines except for local

resistance patternsLancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7



• List of restricted antibiotics

– Removal of specific antibiotics from formulary

– Restriction of use by requiring preauthorization by a

specialist

– Allowing use for only 72 h with mandatory approval

for further use

• Bedside consultation

• Assessment of patients’ adherenceLancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7

Current Evidence on Hospital Anti-

microbial Stewardship Objectives

• Systematic Review/Meta-analysis of 145 studies

• Guideline-adherent empirical therapy:

Mortality RRR 35% (p<0⋅0001)

• De-escalation: Mortality RRR 66% (p<0⋅0001)

• Therapeutic drug monitoring: RRR 50% for

nephrotoxicity (p=0.02)

• Bedside consultation: RRR 66% with S. aureus

bacteremia mortality (p=0.008)Lancet Infect Dis. Online 3/2/16 http://dx.doi.org/10.1016/S1473-3099(16)00065-7

NATIONAL ACTION PLAN GOALS

• Slow the Emergence of Resistant Bacteria and

Prevent the Spread of Resistant Infections.

• Strengthen National One-Health Surveillance

Efforts to Combat Resistance.

• Advance Development and Use of Rapid and

Innovative Diagnostic Tests for Identification

and Characterization of Resistant Bacteria.White House. National action plan for combating antibiotic-resistant bacteria. 3/15

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating

_antibotic-resistant_bacteria.pdf

Goal to Slow the Emergence of

Resistant Bacteria & Prevent Spread

of Resistant Infections by 2020• “Judicious use of antibiotics … essential to

slow the emergence of resistance …”

• Outcomes will include:

– Antibiotic stewardship programs in all acute care

hospitals & improved antibiotic stewardship

across all healthcare settings

Based on recommendations from CDC Core Elements of

Hospital Antibiotic Stewardship Programs. http://www.cdc.gov/getsmart/healthcare/pdfs/core-elements.pdf

White House. National action plan for combating antibiotic-resistant bacteria. 3/15

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-

resistant_bacteria.pdf

Goal to Slow the Emergence of

Resistant Bacteria & Prevent Spread of

Resistant Infections by 2020

• Outcomes (continued)

– Reduction of inappropriate antibiotic use by 50%

in outpatient & by 20% in inpatient

– Antibiotic Resistance Prevention Programs in all

states

– Elimination of medically-important antibiotics in

animals.

– Veterinary oversight of medically-important abxWhite House. National action plan for combating antibiotic-resistant bacteria. 3/15

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-

resistant_bacteria.pdf

LOCATIONS OF STEWARDSHIP

PROGRAMS

• “Expansion to ambulatory surgery centers,

dialysis centers, nursing homes and other long-

term care facilities, and emergency departments

and outpatient settings is also recommended.”IDSA/SHEA Guideline. Clin Infect Dis (2016). doi: 10.1093/cid/ciw118. First

published online: Apr 13, 2016

http://cid.oxfordjournals.org/content/early/2016/04/11/cid.ciw118.full

Core Elements of Antibiotic

Stewardship Programs – CDC

• 2014 – Core Elements of Hospital Antibiotic

Stewardship Programs

• 2015 – Core Elements of Antibiotic Stewardship

for Nursing Homes

• 2016 – Core Elements of Outpatient Antibiotic

Stewardship

Vital Signs: Improving Antibiotic Use

Among Hospitalized Patients

• ~60% receive at least 1 day of antibiotic

• Incorrect in up to 50%

– Indication, choice, or duration can be incorrect

• 30%, outside of critical care, unnecessary

• Used for longer than recommended durations

• Used to treat colonizing or contaminating

organismsCDC. MMWR 14;63:194-200

ANTIBIOTIC STEWARDSHIP IN

NHs

• Up to 70%/y receive antibiotics

• Up to 75% of antibiotics Rx’s incorrectly

• “CDC … recommends that all nursing homes

take steps to improve antibiotic prescribing

practices and reduce inappropriate use.”CDC The core elements of antibiotic stewardship for nursing homes, 2015.

http://www.cdc.gov/longtermcare/index.html.

IDENTIFY OPPORTUNITIES TO

IMPROVE OUTPATIENT RX

• Identify high-priority conditions for intervention

which commonly lead to deviation from best

practices for prescribing

– Overprescribed – not indicated

• eg, not indicated for acute bronchitis, nonspecific URI,

viral pharyngitis

– Overdiagnosed – may be appropriate but without

fulfilling diagnostic criteria

• eg, GAS pharyngitis diagnosed without testing for GASCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16.

http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e



– Misprescribed – may be indicated but wrong drug,

dose or duration

• eg, azithromycin rather than amox or amox/clav for acute

uncomplicated bacterial sinusitis

– Watchful waiting or delayed use is appropriate but

underused

• eg, AOM, acute uncomplicated sinusitis

– Underused or timely use not recognized

• eg, missed STD or severe bacterial infections such as

sepsisCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12 11/11/16.

http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e



• Identify barriers that may lead to deviation

from best practices, eg Clinician:

– Knowledge about best practices and guidelines

– Perception of patient expectations for antibiotics

– Perceived pressure to see patients quickly

– Concerns about decreased patient satisfaction with

clinical visits when antibiotics are not prescribedCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12

11/11/16. http://www.cdc.gov/mmwr/volumes/65/rr/rr6506a1.htm?s_cid=rr6506a1_e



• Establish standards for antibiotics based on

evidence-based diagnostic criteria and treatment,

eg:

– Implementation of clinical practice guidelines

– If applicable, developing facility- or system-specific

practice guidelines

• Establishing expectations for appropriate prescribingCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


ACTION. Clinicians implement at least

1 of following

• Use evidence-based diagnostic criteria &

treatment recommendations from guidelines

• Use delayed prescribing practices or watchful

waiting, when appropriate

– Postdated Rx with instructions for filling

– Patient call or pick up Rx if worsen or no

improvement

– Provide symptomatic relief suggestionsCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


ACTION. Outpatient & health care

system leaders at least 1 of following

• Provide communication skills training for

clinicians

– Strategies to address patient concerns regarding:

• Prognosis, benefits, and harms of treatment

• Management of self-limiting conditions

– Clinician concerns

• Managing patient expectations for antibiotics during a

clinical visitCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12




• Require explicit written justification in the

medical record for nonrecommended abx Rx’ing

– Hold clinicians accountable in medical record for

decisions

• Provide support for clinical decisions.

– Clinical decision support in electronic or print form

during the typical workflow

– Can facilitate diagnoses and effective management

of common conditions



• Use call centers, nurse hotlines, or pharmacist

consultations as triage systems to prevent

unnecessary visits.

– These resources can be used to reduce unnecessary

visits for conditions that do not require a clinic visit,

such as a common cold.Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


TRACKING & REPORTING. Clinicians

implement at least 1 of following

• Self-evaluate antibiotic prescribing practices

– Use self-evaluations to align prescribing practices

with updated evidence-based recommendations and

clinical practice guidelines

• Participate in CME and quality improvement

activities to track and improve antibiotic

prescribingCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


TRACKING & REPORTING.

Outpatient & health care system leaders

at least 1 of following

• Implement at least one antibiotic prescribing

tracking and reporting system

– For high-priority conditions that have been identified

– % of visits leading to Rx

– Complications of use and resistance trends

– Outcomes can be tracked and reported by individual

clinicians (which is preferred) and by facilitiesCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


TRACKING & REPORTING.



• Assess and share performance on quality

measures and established reduction goals

addressing appropriate prescribing from health

care plans and payers

– National Strategy for Combating Antibiotic-

Resistant Bacteria aims to reduce inappropriate use

by 50% for monitored conditions in outpatient

settings by 2020

– Healthcare Effectiveness Data and Information Set

(HEDIS) quality measures

Current National Committee for Quality

Assurance HEDIS Measures – 2016

• Appropriate treatment for children with URI

– Diagnosed with URI and no antibiotic Rx

• Appropriate testing for children with pharyngitis

– Diagnosed with pharyngitis, Rx’d antibiotic, and

received a GAS test

• Avoidance of antibiotic treatment in adults with

acute bronchitis

– Diagnosed with acute bronchitis no antibiotic Rxhttp://www.ncqa.org/hedis-quality-measurement/hedis-measures

EDUCATION & EXPERTISE.

Clinicians educate patients by at least 1

• Use effective communications strategies to

educate patients about when antibiotics are and

are not needed, eg:

– Antibiotics of no benefit for viral infections

– Some bacterial infections (e.g., AOM and sinus

infections) might improve without antibiotics

– Recommendations for symptom management and

when to seek additional care (contingency plan)

– Improves patient satisfactionCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


STRATEGIES FOR STEWARDSHIP

OF ACUTE RTIs IN COMMUNITY

• Raise the public’s “antibiotic threshold”

– Community awareness of stewardship

• Vaccination as a key strategy

• “Covering more territory” to fight resistance

– Pharmacists, Nurses

• An antibiotic “license” to prescribe?

• Stewardship governance in primary care

– Leadership commitment, AccountabilityClin Pulm Med 16;23:1-10


Clinicians educate patients by at least 1

• Educate patients about the potential harms of

antibiotic treatment

– eg, common and sometimes serious side effects:

• nausea, abdominal pain, diarrhea, C. difficile, allergic

reactions, disturbing microbiota

• Provide patient education materials

– Many choices at http://www.cdc.gov/getsmartCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12





• Provide face-to-face educational training

– By peers, colleagues, or opinion leaders, other

clinicians and pharmacists

– Use reinforcement techniques and peer-to-peer

comparisonsCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12




at least 1 of following • Provide CE activities for clinicians.

– Appropriate prescribing, adverse drug events, and

communication strategies about appropriate Rx’ing

– Training to assess patient expectations, discuss risks

& benefits, provide recommendations for when to

seek medical care if worsening or not improving

(contingency plan), and assess patient’s

understanding of communicated information

• Decreases inappropriate antibiotic prescribingCore Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12





• Ensure timely access to persons with expertise

– eg, pharmacists or medical and surgical consultants

who can assist clinicians in improving antibiotic

prescribing

– Pharmacists with ID training effective are important

members of stewardship programs

• Improved patient outcomes and overall cost savings for the

hospital Core Elements of Outpatient Antibiotic Stewardship. MMWR Recomm Rep 16;65;1-12


Effect of Behavioral Interventions on

Inappropriate Antibiotic Prescribing

• RCT – 248 primary care clinicians in Boston and

LA over 18 months

• Randomized to receive 0, 1, 2, or 3 interventions

– All groups received education and observation

– Control group had no study intervention

– Suggested alternatives intervention in EHR

• With acute RTI triggered clinician decision supports and

electronic order sets suggesting nonantibiotic treatmentsJAMA 16;315:562-70



Interventions continued

– Accountable justification intervention (EHR)

• Prompted clinicians to enter free-text justifications for

prescribing antibiotics

• Triggered for both inappropriate and appropriate antibiotic

RTI diagnoses

– Peer comparison intervention

• Sent monthly emails to clinicians that compared their

antibiotic prescribing rates with those of “top performers”

(lowest inappropriate prescribing rates)JAMA 16;315:562-70



• Antibiotic Rx rates baseline vs. month 18

– Control group 24.1% to 13.1%

– Suggested alternatives 22.1% to 6.1% P=0.66

– Accountable justification 23.2% to 5.2% P<0.001

– Peer comparison 19.9% to 3.7% P<0.001

• Significant reductions in inappropriate antibiotic

prescribing

– Accountable justification and peer comparisonJAMA 16;315:562-70



• Treat bacterial infection only

• Judicious antibiotic prescribing principles

– Use pharmacokinetic/pharmacodynamics to choose

most effective agents and appropriate dosage

– Optimize the duration of therapy

– “Know your bugs”: local antibiograms

– Use abx associated with < selection of resistance

• Prescription strategies

– Immediate vs delayed vs no RxClin Pulm Med 16;23:1-10



• Raise the public’s “antibiotic threshold”

– Community awareness of stewardship

• Vaccination as a key strategy

• “Covering more territory” to fight resistance

– Pharmacists, Nurses

• An antibiotic “license” to prescribe?

• Stewardship governance in primary care

– Leadership commitment, AccountabilityClin Pulm Med 16;23:1-10

RTI 1st-LINE ANTIBIOTIC USE2010-11 Nat Amb Med Care Survey

• AOM 67%

– Amoxicillin or amoxicillin/clavulanate

– ~12% macrolide, ~17% ceph

• Acute bacterial sinusitis ~37%

– Amoxicillin or amoxicillin/clavulanate

– ~27% macrolide, ~10% FQ

• GAS pharyngitis Peds ~60%, Adult ~40%

– Penicillin or amoxicillin

– Peds ~20% macrolide, 5% ceph

– Adult ~12% amox/clav, ~35% macrolideJAMA IM 16;176:1870-1. Letter

Duration of Antibiotics in CAP:

Multicenter RCT

• Duration minimum of 5 d if responding and

stable vs. standard therapy (at least 10 d)

– 5 d duration in 70% of patients in intervention group

– Clinical success ~94% intervention vs. ~93% control

(P = 0.33)

• Stopping antibiotics if clinically stabile after a

minimum of 5 d is not inferior to traditional

treatment durationJAMA Intern Med 16;176:1257-65

Short course, d Long course, d

CAP 3-5 7-10

Nosocomial

pneumonia

< 8 10-15

ABECB < 5 > 7

AOM (varies with

age & severity)

Not severe: 5 (>6y);

7 (2-5y); < 3 (>2y)

10 (2y, severe)

Acute bact sinusitis 5-7 10

Uncomp cystitis 3 (FQ, TMP/SMX) 7-10

Pyelonephritis 5-7 (FQ) 10-14

Cellulitis 5-6 10

SHORT-COURSE THERAPY

Spellberg. JAMA IM 15;176:1254-5 Pharmacist’s Letter/Prescriber’s Letter. 11/16 & 12/16

DURATION OF THERAPY

• Finish all the pills even if you feel better

– Age old instruction to patients

– Increase in curing the infection?

– Reduce resistance by eradicating all the organisms?

– Prevent a relapse of the infection?

• Historically in multiples of 7 d (eg, 7-14 d) for

many common infections

– Often not based on clinical outcome studiesJAMA Intern Med 16;176:1257-65

Pharmacist’s Letter/Prescriber’s Letter. November 2016

DURATION OF THERAPY

• Shorter courses now have demonstrated efficacy

for some common infections

• Potential benefits of shorter courses of antibiotic

– Lower resistance with less normal flora exposure

– May reduce cost

– May reduce risk of adverse effects

• Fewer antibiotic side effects

• Less superinfections from altering normal flora (C. diff)

– May increase adherenceJAMA Intern Med 16;176:1257-65

Pharmacist’s Letter/Prescriber’s Letter. November 2016

The New Antibiotic Mantra

• No evidence for – “illogical … statement that to

prevent antibiotic resistance, it is necessary … to

complete the entire prescribed course of therapy,

even after resolution of symptoms”

• Longer courses increase selection for resistance

• “Overtreating … is likely a major source of

selective pressure that drives antibiotic

resistance in society”Spellberg B. edit. JAMA IM 15;176:1254=5


• Shorter courses “greatly preferable”

• Customize duration to the patient’s response

– Contact clinic if symptoms resolve before

completing antibiotic – assess for stopping early

• Clinicians “should be encouraged to allow

patients to stop antibiotic treatment as early as

possible on resolution of symptoms”Spellberg B. edit. JAMA IM 15;176:1254=5


• “Ultimately, we should replace the old dogma of

continuing therapy past resolution of symptoms

with a new, evidence-based dogma of “shorter is

better.”Spellberg B. edit. JAMA IM 15;176:1254=5

ANTIBIOTIC STEWARDSHIPInfection & Syndrome Specific Interventions

• CAP

– Improving diagnostic accuracy, tailoring of therapy

to culture results and optimizing the duration of

treatment to ensure compliance with guidelines

• UTIs

– Many have asymptomatic bacteriuria and not

infections

– Ensure appropriate therapy based on local

susceptibilities and for the recommended durationCDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014.

http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html

UTI in Advanced Dementia

• 19% of treated UTIs met minimal criteria for

antibiotics

• “well recognized that asymptomatic bacteriuria should

not be treated”

• UTI diagnosis is often made – but should not be

made – vague changes in MS without objective signs

• Urinalyses and UCs are often positive in advanced

dementia

– Negative tests rule out but positive test do not necessarily

justify the use of antibiotics

NEJM 15;372:2533-40


• Skin and soft tissue infections

– Do no use overly broad-spectrum antibiotics and

ensure correct duration of treatment

• Empiric coverage of MRSA infections

– In many cases, therapy can be stopped if the patient

does not have an MRSA infection or changed to a ß-

lactam if the cause is MSSACDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014.



• C difficile infections

– Stop unnecessary antibiotics which often does not

occur

• Treatment of culture proven invasive infections.

– Provides information to tailor antibiotics or

discontinue them if contaminantsCDC Core Elements of Hospital Antibiotic Stewardship Programs. 2014.



• Upper respiratory infections not otherwise

specified

– Antibiotic use does not enhance illness resolution or

prevent complications and is not recommended

• Acute pharyngitis

– Limit antibiotic use to those with highest liklihood of

GABHS.

– Penicillin is preferredCDC Get Smart. Updated 4/17/15 http://www.cdc.gov/getsmart/community/materials-

references/print-materials/hcp/adult-approp-summary.html


• Rhinosinusitis

– Most cases viral – assess criteria for bacterial

– Reserve antibiotics for those that meet criteria for

bacterial etiology with moderate to severe symptoms

– Use most narrow-spectrum agent against S.

pneumoniae and H. influenzae

• Uncomplicated acute bronchitis

– Routine antibiotic use not recommended regardless

the duration of coughCDC Get Smart. Updated 4/17/15 http://www.cdc.gov/getsmart/community/materials-

references/print-materials/hcp/adult-approp-summary.html

WHAT SHOULD PATIENTS BE

TOLD ABOUT THEIR ANTIBIOTIC?

• Clear instructions on intended duration

• Emphasize importance of taking properly

• What to do when symptoms resolve:

– Should they contact the office to discuss?

– Should they complete the prescribed course, even if

symptoms resolve?

• Dispose of remaining doses to avoid temptation

to self-treat in the futurePharmacist’s Letter/Prescriber’s Letter. November 2016

Physicians should be comfortable with making

the following statement to most of their patients

with acute RTIs:

“For your infection, there is an ∼1 in 4000

chance that an antibiotic will prevent a serious

complication, a 5%–25% chance that it will

cause diarrhea, and an ∼1 in 1000 chance that

you will require a visit to the ED because of a

bad reaction to the antibiotic.”

Clinical Infectious Diseases 08;47:744-6. Editorial

Antibiotic Stewardship – What is It? · UND School of Medicine & Health Sciences Altru Family...

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