9/13/18 · 2018-09-13 · 9/13/18 6 Feedlot Use of Antibiotics §19 million poundsof antibiotics per yearare fed to farm animals, and 88 percent of that amount was fed at low doses,

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Antibiotic Stewardship for Nurse Practitioners

§ Richard Yates, M.D.

The Story of Antibiotic Stewardship

§One President§4 cops§5 Ghosts§2 Demons

Antibiotic Stewardship

§The Need for Stewardship§The Mechanisms of Resistance§The Implementation of Stewardship§The Results of Stewardship

NATIONAL ACTION PLAN FOR COMBATING ANTIBIOTIC-RESISTANT

BACTERIAMARCH 2015

The National Action Plan for Combating Antibiotic-resistant Bacteria provides a roadmap to guide the Nation in rising to this challenge . Developed in response to Executive Order 13676: Combating Antibiotic-Resistant Bacteria—issued by President

Barack Obama on September 18, 2014…efforts to minimize the development of resistance by ensuring that each patient receives the right antibiotic at the right time at the right dose for the right duration.

ABS - Requirements

§Presidential Mandate 2015§CDC Guidelines§Joint Commission Requirements§State Guidelines§Nursing Home ABS requirements - National

§ September 18, 2014: Executive Order 13676: National Strategy for Combating Antibiotic-Resistant Bacteria (CARB)

§ March 2015: National Action Plan for CARB

§ September 2015: Presidential Advisory Council appointed for Combating Antibiotic Resistant Bacteria (CARB)

§ Annually in November: Get Smart About Antibiotics Week

§ January 1, 2017: New TJC Standard for Antimicrobial Stewardship

§ By the end of 2017: CMS to mandate antimicrobial stewardship programs as a requirement for participation

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What is Antibiotic Stewardship?§Antimicrobial Stewardship is a coordinated approach that utilizes multiple methods to improve antibiotic use and improve patient outcomes

§Implementing Antimicrobial Stewardship programs help ensure patients receive:

§ The right antibiotic, at the right dose, at the right time, and for the right duration for a specific patient

§Antimicrobial Stewardship programs also educate when antibiotics are NOT needed (ie. viruses, colds, non-infections)

Why is ABS Important?

§Antibiotic use is the main driver for development of resistance

§Antibiotics are the only drug where use in one patient can impact the effectiveness in another

§Several studies show that up to 30% - 50% of in-patient antibiotic use is either unnecessary or inappropriate

Current ThreatsUrgent Threats§ Clostridium difficile§ Carbapenem-resistant Enterobacteriaceae (CRE)§ Drug-resistant N. gonorrhoeae

Serious Threats§ MDR Acinetobacter§ MDR Pseudomonas aeruginosa§ Extended-spectrum �-lactamases in

Enterobacteriaceae (ESBLs)§ Fluconazole-resistant Candida§ Resistant Campylobacter§ Vanc-resistant Enterococcus (VRE)§ Methicillin-resistant S. aureus (MRSA)§ Resistant S. pneumoniae§ Resistant Non-typhoidal Salmonella, Salmonella Typhi,

Antibiotic Resistance Threats in the United States, 2013. CDC. Published online September 16, 2013.

Controlling the Spread of Antimicrobial Resistance in Healthcare

Prevent Infection

Infection Control

Optimize Antibiotic

Use

Antimicrobial Stewardship

Programs (ASPs)

2 Tools to Fight Resistance

Infection Prevention§Recognizing Colonization§Hand Hygeine§Contact Precautions§ Isolation§Environmental

decontaminationAntimicrobial Stewardship

Limiting the drug, dose, and duration of antibiotics

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How Antibiotic Use Drives Antibiotic Resistance

( Or why do these pharmacists keep bothering me about the

choice and dose of antibiotics?)

New Dehli “Superbug” 2010

No Worries, it’s in India!

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Bacteria

+ -Lipid Bilayer

How do drugs gain access to bacteria?

bacteria

drug!

Mechanisms of Resistance

§Target Site Alteration§Efflux Pumps§Enzymes §Access

Bugs fighting back:Antibiotic resistance mechanisms Target Site Alterations

§Gram positive or gram negative organisms§Ribosomal targets§Tetracyclines§Macrolides§Lincosamides§Aminoglycosides

§DNA Gyrase§Fluoroquinolones

§Penicillin Binding Proteins (PBP�s)§Beta-lactams

§D-ala-D-ala§Vancomycin

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Selection vs Mutation

§Mutation:

drug!

• Selection:

drug! drug!

drug!

drug!

drug!

drug!

Once drugs �are in,� how do bacteria try to eliminate them?

Gram negative bacteria

drug!drug!

drug!

βL

Antibiotics:Miracle drugs, it started out so well, but ….

History of antibiotic discovery and concomitant development of antibiotic resistance.

Julian Davies, and Dorothy Davies Microbiol. Mol. Biol. Rev. 2010;74:417-433

Where does resistance happen?§The GI tract contains over 1 trillion bacteria§More opportunity for transposon resistance§More opportunity for induction resistance§Relatively low levels of antibiotics accelerate resistance development

§Longer duration of treatment increases resistance developement

We are using more antibiotics!

Findings Between 2000 and 2010,

consumption of antibiotic drugs increased

by 36% (from 54083964813 standard units

– doses- to 73620748816 standard units).

Brazil, Russia, India, China, and South Africa accounted for 76% of this increase.

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Feedlot Use of Antibiotics

§19 million pounds of antibiotics per year are fed to farm animals, and 88 percent of that amount was fed at low doses, which favor evolution of antibiotic resistance because they do not kill all bacteria in a colony.

§36 million antibiotic prescriptions at 1.5 grams per prescription.

§ (36 million scripts) (1.5 g) = 54 million grams§8.6 trillion grams in feedlots vs 54 million grams in

prescriptions

The ecology of resistance:Selection and transmission

Selection with antibiotics

Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

§ Int J Microbiol. 2011; 2011: 312956.§ Published online 2011 Jan 24. doi: 10.1155/2011/312956§ PMCID: PMC3034945§ Susanne Schjørring* and Karen A. Krogfelt

The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes.

“Could the microflora of the human colon, normally considered innocuous or beneficial, be playing a more sinister role in human health as a reservoir for antibiotic resistance genes?” was the hypothesis set by Salyers and coworkers [28].

Commentary:The gut is the epicentre of antibiotic resistance - Jean Carlet

Many horizontal gene transfers occur among Enterobacteriaceae [25,26] and between pathogens and the gut flora, most notably when the gut barrier is altered [27]

Mechanisms of Resistance

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Antibiotic Resistance

§Carbapenem-resistant P. aeruginosa §Extended-spectrum ß lactamase-producing K. pneumoniae (ESBL-K)§Vancomycin-Resistant Enterococci (VRE)§Methicillin-resistant S. aureus (MRSA)§Aminoglycoside-resistant P. aeruginosa

Enzymes in Gram Positive vs. Gram Negative Bacteria

Gram negative bacteria

Gram positive bacteria

EnzymesGram Positive§S. aureus§1940: PCN susceptible§late �40s: PCN resistant due to penicillinase§Nafcillin/Methicillin/Oxacillin stable against

penicillinase§Resistance due to PBP alterations

Categories of Beta Lactamases

§Transmitted:

§chromosomal vs. plasmid vs. transposon (MRSA - Penicillinase)

§Production:

§basal vs. inducible ( Amp – C)

§Spectrum:

§Narrow (Penicillinase) vs. extended (ESBL) vs. very extended – (KPC)

Level of Resistance- Different Enzymes, Different Susceptibilities

256<0.5<0.5<0.5Ceftazidime

>1024256>10248AmpicillinTEM-1 (-) TEM-1 (+) TEM-26 (-) TEM-26 (+)

E. coli, MIC K. pneumoniae, MIC

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Problem Hospital Organisms

§MRSA (most hospitals > 50%)

§VRE (most hospitals > 30%)

§Multi-drug resistant GNRs (varies widely)

§Pseudomonas aeruginosa§Acinetobacter spp.

§Enterobacter spp.

§E. coli§Klebsiella spp.

§Serratia marcescens

5 Organisms that Haunt Nursing Homes

Amp C

ESBLCRE VRE

C. diff

What is Amp C Beta –lactamase?

§Relatively narrow resistance seen to ampicillin and 1st generation cephalosporins

Amp-C Beta-Lactamase Producing Organisms§Serratia species

§Citrobacter species

§Enterobacter species

§Other gram negatives (less common)

Enterobacter (Amp-C) Infections§Trend toward protection from developing

resistance when combination with aminoglycoside

Kaye K. et. al. Antimicrob Agents Chemother.2001;45:2628-30.

Cases Control p-value

Mortality 26% 13% 0.01

LOS (days) 29.5 19 <0.001

Cost $79,000 $40,000 <0.001

What is ESBL?

§Extended Spectrum Betalactamase§Broad spectrum resistance to PCNs and cephalosporins

§Often resistant to other antibiotics

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ESBL vs. AmpC

ESBL Amp C E. coli Resistance – InductionInitial vs. Confirmatory Testing

Antibiotic MIC Interpret

Amikacin <=16 SAmox/clav <=8 SCefazolin >2 RCefepime <=8 SCefoxitin <=8 SCefotaxime >8 RCeftriaxone <=8 SCefuroxime <=8 SCiprofloxacin >2 RGentamicin 8 RMeropenem <=4 SPiperacillin/T <=16 STobramycin 4 STrimeth/Sulfa >2/38 R

ESBL

Antibiotic MIC Interpret

Amikacin <=16 SAmox/clav >8 RCefazolin >2 RCefepime >8 RCefoxitin <=8 SCefotaxime >8 RCeftriaxone >8 RCefuroxime >8 RCiprofloxacin >2 RGentamicin 8 RMeropenem <=4 SPiperacillin/T >16 RTobramycin 4 STrimeth/Sulfa >2/38 R

ESBL Treated with �Susceptible�Cephalosporins

§43 patients with ESBL infection treated with cephalosporin

§27 patients (63%) failed cephalosporin therapy

§4 of 16 patients cured on therapy were on combination with active agent (aminoglycoside)

2 Demons that Release the Monsters

Ceftriaxone and Levofloxacin Drivers of ESBLs

§Extended spectrum cephalosporins

§Fluoroquinolones

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3rd Generation Resistance and Antibiotic Use

Rice, Pharmacotherapy 1999.

0

5

10

15

20

25

30

Q194

Q2 Q3 Q4 Q195

Q2 Q3 Q4 Q196

Q2 Q3 Q4 Q197

Q2 Q3 Q40

100

200

300

400

500

600

700

800Ceftaz Res Pip/Tazo Res

Ceftazidime UsePip/Tazo Use

% R

esis

tanc

e

Gra

ms

of C

efta

zidi

me

Risk Factors for Resistance to Broad-Spectrum Cephalosporins

§477 patients, all isolates initially sensitive§49 isolates developed resistance§broad-spectrum cephalosporins a risk factor RR = 2.3,

p = 0.01§19% patients treated with broad-spectrum

cephalosporin developed resistance§29% of bacteremic patients developed resistance

Kaye K. et. al. Antimicrob Agents Chemother.2001;45:2628-30.

Emergence of Enterobacter spp. Resistance in Bacteremias

§Multi-center evaluation, 129 patients§Previous 3rd generation cephalosporins associated

with multi-resistant Enterobacter spp. (69% vs. 20%)

§Multi-resistance associated with higher mortality (32% vs. 15%)

§Emerging resistance during cephalosporin, aminoglycoside, other beta-lactam (19% vs. 1% vs. 0%)

Chow J et al. Ann Intern Med. 1991;115:585-590.

Spreading Resistance

§Once we create the monster, we multiply it and spread it around!

ESBL: The steps from contamination to infection

Healthy individual

Intestinal colonization (low conc)

Acquisition of ESBL by human contact & food

Selection of ESBL (high conc)

Destruction of normal intestinal flora by antibiotics

Breach of natural barriers (surgery, catheters, chemotherapy etc)

Patient with invasive infection

Many Some Few

Carbapenemase:KPCs

§Suped up ESBL §Hydrolyzes carbapenems

§Increasing prevalence§Limited drug choices§Colistin, tigecycline, fosfomycin, clorpactin

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Vicious Cycle é ESBLs

é CarbapenemUse

éCarbapenemase

é Tigecycline, Colistin

•Nursing Home•LTAC•Hemodialysis

FluoroquinolonesE-S Cephalosporins

Quinolones Increase Mutation Frequency

§Fluoroquinolone Enhances the Mutation Frequency for Meropenem-Selected Carbapenem Resistance in Pseudomonas aeruginosa

How do quinolones cause carbapenem resistance?§Quinolones and carbapenems use same porin to

enter§Point mutations in porin configuration effect both

drugs§Meropenem and doripenem can use different

porins to gain access

Cross Resistance

bacteria

CiproImipenem

Meropenem

�D2 porin�

Carbapenems and IV CiproQuinolones cause

Carbapenem Resistance

§ Int J Antimicrob Agents. 2007 Nov;30(5):409-14. Epub 2007 Sep 11.

§Exposure to quinolones is associated with carbapenem resistance among colistin-susceptible Acinetobacter baumannii blood isolates.

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Selection for VRE

VRE Selection§Peptostreptococcus§Peptococcus

§Klebsiella sp.§B. fragilis§E. coli

CTX, metro, FQ

• Enterococcus

Factors Associated With Vancomycin-Resistant Enterococci in the Literature

IV and Oral Vancomycin use

VRETransplant

patientsQuinolone use

Widespread Broad SpectrumAntibiotic Use (Cephalosporins)

VRE Trends Over TimeVancomycin 1958

C. difficile 1977

3GC mid 1980�sFQ 1988

Vancomycin Introduced

CDI described FQ�s introduced

3rd Cephs

Non-ICU

ICU

Martone WJ. Infect Control Hosp Epidemiol. 1998;19:539-545NNIS Antimicrobial Resistance Surveillance Report. 1999

ANTIBIOTICS AND VRE

0 1 2 3 4

CeftriaxoneCeftazidimeVancomycinClindamycinCefuroxime

Ticar/Clav

Relative Risk of Acquiring VRE

Tokars JI et al, Infect Control Hosp Epidemiol 1999;20(3):171-5

Effect of Antibiotic Selection on VRE Colonization

§Prospective three-phase sequential study§16 month duration§Phase 1-Ceftazidime empiric agent for febrile

neutropenic episodes§Phase 2-Switch to Pip/Tazo§introduction of improved infection control

§Phase 3-Switch back to CTZ§infection control continued

Bradley SJ, et al. JAC 1999;43:261-266

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57%

29%

8%

38%

0%

10%

20%

30%

40%

50%

60%

Phase 1**Month 1-4

Phase 2aMonth 5-8

Phase 2b**Month 9-12

Phase 3Month 13-16

Rate

of G

RE C

olon

izat

ion

Effect of Antibiotic Selection on VRE* Colonization

* Glycopeptide Resistance

** P<0.0001Bradley, et al JAC 1999.

Bradley, Pharmacotherapy 2000; 20:203S-212S.

CTZ DiscontinuedP/T Started

P/T DiscontinuedCTZ Restarted

Ciprofloxacin & Levofloxacin GU Scripts

Source: SDI/ IMS Total GU TRxs

ciprofloxacin

2005-2007 incr of 33%(1.3M scripts)

Introduction of generic

ciprofloxacin

5-Year E coli % Resistance Trendfrom TRUST 2003 to 2007

AntimicrobialAgent

2003N=91

5

2004N=760

2005N=1303

2006N=143

5

2007N=172

4

5-year

% Incr

Ampicillin

Trimeth/sulfa

Ciprofloxacin

Levofloxacin

Gentamicin

34.6

16.8

9.1

9.1

4.0

39.7

19.3

9.5

9.5

4.9

41.0

19.5

9.89.4

4.9

44.7

20.4

14.814.0

6.8

48.3

26.3

19.618.9

7.9

13.7

9.5

10.5

9.8

3.9

2015 E.coli resistance to quinolones = 35%

Beyond ESBL: carbapenem resistance- the ultimate horror scenario

Resistance to

ESBL producing Enterobacteriaceae

PenicillinsCephalosporins

Carbapenem resistant Enterobacteriaceae(VIM,NDM-1, KPC-2,oxa-48)

PenicillinsCephalosporinsCarbapenems+ others

Overall Summary

Amp C ESBL KPC VRE

Drivers ES cephs

Clav

Cefoxitin

Imipenem

ES cephs

FQ

Cephs

FQs

Cephs

Clinda

FQs

Treatments Cefepime

AMG

FQs

Carbs

Carbs

Colistin

Colistin

Tigecycline

Dapto

Linezolid

Synercid

Tigecycline

Antibiotic Use and the Risk of C. dificile Colitis

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Antibiotics and CDIAntibiotics increase risk of CDI

1. disrupt normal colonic flora2. selecting for resistant C difficile strains

Clindamycin: 1970 and 1908’s§ Initial drug associated with CDI § published reports documenting control of

outbreaks due to highly clindamycin resistant strains with restricted clindamycin use

2nd and 3rd generation Cephalosporins: 1990’s§ Widespread use starting in the 1990s§ Associated with increased rates of CDI as

compared with β-lactams (pip-tazo)

Antimicrob Chemother. 1997 Nov;40(5):707-11.; Aliment Pharmacol Ther. 1998 Dec;12(12):1217-23. J Hosp Infect. 2003 Jun;54(2):104-8.; Infect Control Hosp Epidemiol. 1994 Feb;15(2):88-94.

CDI and Quinolones

Epidemic in Quebec 2004: demonstrated increased rates of CDI with:

§Exposure to 3rd gen cephalosporins (OR 3.8)

§Exposure to fluoroquinolones (OR 3.9)Subsequent studies have demonstrated

significant increases in CDI associated with fluoroquinolones

§Texas: increase in fluoroquinolone use preceded the beginning of outbreak by 9 months (P<0.001)

N Engl J Med 2005; 353:2442-2449; Muto et al Infect Control Hosp Epidemiol 2005;26:273–280; Clinical Infectious Diseases 2004;38:640–64

Clinical Impact

Ciprofloxacin Ceftriaxone Amp + gent

Drug (2 days) $6.16 $7.72 $26.42

2+ Hospital Days $2600 $2600

Differential Cost $62,264.20 $44,069.44

C. Difficile Infection

-Primary: $2,871-$4,846

-Recurrent: $13,655-$18,067

-Annual US: $436 million – $3 billion +

VRE Case - $4,479 - $77,558

What Does an ASP Do?

Resistance Creation

§We can cause resistance to happen by the antibiotics we choose, the dose we use, the duration of infusion time, and the total duration of treatment

§Not all antibiotics are equal!

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Optimizing Antimicrobial Therapy

Pharmacodynamics

[C] @Infection

Site

PathogenMIC

DrugPK

Outcome

• Absorption• Distribution• Metabolism• Excretion

• Time-Dependent Killing• Concentration-Dependent Killing• PAE

• Bacterial Counts• Mortality• Rate of Symptom

Resolution / Free Period

Clinical Outcomes Better With Antimicrobial Management Program

RR 2.8 (2.1-3.8) RR 1.7 (1.3-2.1) RR 0.2 (0.1-0.4)

Perc

ent

AMP = Antibiotic Management ProgramUP = Usual PracticeFishman N. Am J Med. 2006;119:S53.

Antibiotic Choice & ResistanceBeta-lactams

§Less Resistance More Resistance

§Penicillins Cephalosporins§Cefotaxime Ceftriaxone§Cefepime Ceftazidime§Meropenem Imipenem

Type-I Beta-LactamasesPotential for Induction of Beta-lactamases

Danziger et al. AJHP. 1995

Antibiotic Use - Help or Hurt• Some antibiotics – 3rd Gen Cephalosporinsand quinolones – drive resistance higher

• Some antibiotics – penicillins and aminoglygosides – drive resistance lower

• Within each class, some are better than others

Antibiotic Infusion Time and Resistance

Less Resistance More resistanceB-Lactams -less, longer more, shorter(PI Zosyn, Merrem) (Conventional dose)

Aminoglycosidesmore, shorter less, longer(Once daily dosing) (“80mg q 8”)

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30-min infusion

n=573-hour infusion

n=49 p-value

Median (IQR)

ICU LOS, d 12.0 (6.9-19.5) 9.1 (5.5-14.5) 0.032Total hospital LOS,

d14.5 (9.0-24.3) 10.5 (6.9-16.6) 0.029

Duration of

meropenem therapy,

d

6.0 (4.0-10.0) 6.0 (3.0-9.1) 0.448

Duration of total

antibiotic therapy, d10.0 (6.0-16.0) 9.0 (5.0-14.8) 0.203

Ventilator days 8.0 (6.0-16.0) 6.0 (3.5-17.0) 0.199n (%)

In-hospital mortality 25 (44) 15 (31) 0.115

2012 Initiative- PI Merrem Meropenem1gram over 30-minutes vs. 500mg over 3-hours

1gm Q8H or Q12HInfused over 30 min

500mg Q6H, Q8H, or Q12H over 3 hours

Number of patients 25 44Median LOS in ICU, d 12.5 8.5Median duration of

meropenem therapy, d 14.5 10.5

Median duration of total antibiotic therapy, d 6 5.75

Median ventilator days*, d 14 6

Number of deaths 13 14

Death Rate (%) 52% 32%

Strategies of ASP§Avoid ceftriaxone, ceftazidime, cefoxitin§Avoid imipenem, quinolones§Promote penicillins §Promote lower dose, prolonged infusion§Promote narrowing and shortening antibiotic treatment

ASP Strategies§Zosyn =primary broad spectrum antibiotic§Unasyn for Pneumonia§Prolonged infusion housewide§Limit AG to 3 days§Limit azithro/ fq to 5 days in CAP§PI Zosyn, Cefepime, Merrem§CI Vancomycin

RESULTS

96

96

ABS

Acute care hospitals

Long-term care

hospitals

Skilled nursing facilities

Consistent Results Across Healthcare SettingsAcute Care Hospitals

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

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Carbapenem-resistant P. AeruginosaNHSN – 25% 2006-2007

Infect Control Hosp Epidemiol. 2008;29(11):996Clin Infect Dis. 2005;40 Suppl 2:S89

Aminoglycoside-resistant P. Aeruginosa

Nationally (2009) – 15%

http://www.cddep.org/ResistanceMap/bug-drug/KP-CS

ESBL-producing Klebsiella

§Huge problem internationally

§2008 Britain = 37%

§2007 India = 46%

§2010 Brazil = 50%

§Multi-national study (2010) : 17%

§US overall average (2009):9%

§TMF-inpatient 2011: 2.7% (HAI < 1%)

Ann Intern Med 2004;140:26-32http://www.cddep.org/ResistanceMap/bug-drug/KP-CS

VRE

§Tyler Hospital – inpatient 2016: 13%§Tyler Hospital – ICU data: 15%§NHSN data 2016-2017 = 22-33%§NNIS 2016– 28% in ICUs

Infect Control Hosp Epidemiol. 2008;29(11):996http://www.cddep.org/ResistanceMap/bug-drug/VRE

1.29

0.86

0.33

0.56

1.861.73

0.730.57

00.20.40.60.811.21.41.61.82

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1/1/

201

1

3/1/

201

1

5/1/

201

1

7/1/

201

1

9/1/

201

1

11/1

/20

11

1/1/

201

2

3/1/

201

2

5/1/

201

2

7/1/

201

2

9/1/

201

2

11/1

/20

12

1/1/

201

3

3/1/

201

3

Spen

ding

in d

olla

rs p

er a

djus

ted

patie

nt d

ay (b

lue

line)

month

Fluoroquinolone usage and HA-CDI

HA

-CD

I rate (per 1000pt days -purple)

Revisions to PNA order set

Cleaning contract Changed – Ifx Control

Efforts Aimed at HA-CDI Reduction

Medical StaffEducational tool

Efforts Aimed at HA-CDI ReductionRevisions to PNA order set

Medical StaffEducational tool

Cleaning contract

Changed – Ifx Control

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ASP and Cephalosporin Use

§ Design: § Prospective evaluation of antimicrobial

management program implemented § Goal: to minimize inappropriate use of 3rd-

generation cephalosporins, broadened to audit use of other antimicrobials

§ Time period: 7 years§ 3 interventions: choice, shorter duration, switch

from IV to PO§ Assessed incidence of C. difficile, resistant

Enterobacteriaceae, VRE, and MRSA in NNIS system hospitals of comparable size

§ Reduction in CDAD (p=0.002)

Carling P, et al. Infect Control Hosp Epidemiol. 2003;24:699-706.

NNIS = National Nosocomial Infections Surveillance system

House-wide implementation of PI Merrem

§ Implement PI protocol for all adult patients who receive meropenem infusion via therapeutic substitution§1g q 8h à 500mg q 6h over 3 hours§Automatically adjust for renal function by clinical

pharmacist

Estimated CLCr (CG in mL/min)

Dose and interval

> 50 500mg q 6h over 3 hours

25-50 500mg q 8h over 3 hours

10-25 500mg q 12h over 3 hours

Hemodialysis 500mg q 12-24; after HD onHD days

CRRT (CVVH) 1g loading dose then 500mg q 8h over 3 hours; 1g q 12h or flow based

Carbapenem-Resistant P. aeruginosa

Aminoglycoside-Resistant P. aeruginosa

Mariana Castanheira et al. Antimicrob. Agents Chemother. 2014;58:833-838

ESBL rates among Enterobacteriaceae isolates collected in 72 U.S. hospitals located in the nine U.S. census regions. Compare to Tyler Hospital

rates

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Antibiotic Spending Trends

US Dollars

110

Decrease in Anti-infective CostsAcute Care Hospital, 2013-17

Source: 127-bed Acute Care Hospital w ith approxim ately 35,000 patient days per year. Average inflation rate = 6% .

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

111

Resistance TrendsAcute Care Hospital, 2015-17

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

Source: 127-bed Acute Care Hospital w ith approxim ately 35,000 patient days per year. Average inflation rate = 6% .

ASP

Acute care

hospitals

LTAC

Skilled nursing facilities

112

Consistent Results Across Care SettingsLong-term Care Hospitals

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

Decrease in C-difficile Hospital Acquired InfectionsLong-term Acute Care Hospital, 2007-2016

Source: C-difficile hospital acquired infections reported at a 51-bed Long-term Acute Care Hospital in Texas from 2007-2016.

Decrease in MDRO Hospital Acquired InfectionsLong-term Acute Care Hospital, 2007-2016

MRSA 9 7 5 4 5 2 1 0 1 1VRE 13 9 8 5 5 5 2 4 0 4

ESBL 2 2 1 1 2 2 2 3 0 0MDR Pseudo 1

Source: C-difficile hospital acquired infections reported at a 51-bed Long-term Acute Care Hospital in Texas from 2007-2016.

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Antimicrobial Expenditure 116

116

ASP

Acute care

hospitals

Long-term care

hospitals

Skilled nursing facilities

Consistent Results Across Healthcare SettingsAcute Care Hospitals

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

117

Clostridium difficile Testing Post ARS ImplementationSkilled Nursing Facilities

The ARS Stewardship Program was implemented in February 2016 at 8 skilled nursing facilities in the Midwest.

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

Decrease in Antimicrobial Cost Per Patient Day

$0.00$2.00$4.00$6.00$8.00

$10.00$12.00$14.00$16.00$18.00$20.00

Feb

'15

Mar

'15

Apr '

15M

ay '1

5Ju

n '1

5Ju

l '15

Aug

'15

Sep'

15O

ct '1

5N

ov '1

5D

ec '1

5Ja

n '1

6Fe

b '1

6M

ar '1

6Ap

r '16

May

'16

Jun

'16

Jul '

16Au

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Cos

t per

pat

ient

day

s ASP Initiation

in facilities

Decrease of average cost by

$5.66 (43%)

118

The ARS Stewardship Program was implemented in February 2016 at 8 skilled nursing facilities in the Midwest.

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

Summary§Antibiotic selection has a significant impact on

resistance patterns §Multiple opportunities in a course of therapy to

intervene to make a positive impact§Initial selection§Dose/interval§Combination§De-escalation§Length of therapy

Things We Know:§Some antibiotics drive resistance more than others

§Some antibiotic dosing drives resistance more than others

§Longer duration = more tonnage of antibiotic use

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21

So we know what not to do…

§Don’t let antibiotic choice and dose depend on the location of the patient

§Don’t choose antibiotics that have high GI tract concentrations

§Don’t dose antibiotics so high that you achieve high GI concentrations

§Don’t give antibiotics so long that you create resistance

Emphasis on Appropriate Use

§Little-to-none new antibiotic development and production

§Resistance §Inappropriate agent(s)§Inappropriate duration§Inappropriate dosing and frequency

§Limit unintended collateral damage

Strategies that work:

§For Beta – lactams – reduce the dose, give over a prolonged interval§More effective§Less resistance

§Ex: Zosyn 3,375 gm over 4 hours q 8h§Merem 500mg over 3 hours q 6h§Ceftazidime continuous infusion

Strategies that work:

§Shorten duration of antibiotic prescribing:§7 days for HCAP§5 days for CAP§5 Days for Intraabdominal infection –

controlled§3 Days for UTI

Coordinated Approach: Community AMS

AMS

Acute Care

SNF/LTAC

Outpatient

125

• AMS Education• General/targe

ted• Information

exchange• Antibiograms• Safe handoffs

Copyright 2017 Antim icrobial Resistance Solutions, Inc. ALL R IG HTS RESERVED.

Ceftriaxone and Levofloxacin

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22

5 Organisms that Haunt Nursing Homes

Amp C

ESBLCRE VRE

C. diff

ASPs = Ghostbusters!