Antibiotic Use in Sepsis and Stewardship - PowerPoint Presentation

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Antibiotic Use in Sepsis and Stewardship

Maureen Campion, PharmDClinical Pharmacy Specialist- Infectious DiseaseUMass Memorial Medical Center

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Disclosure statement

I have no actual or potential conflict of interest in relation to this program/presentation.

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Objectives

Identify the role of antibiotics in sepsis

Describe the challenges to timely antibiotic administrations

List 3 ways to optimize antibiotics in sepsis

Understand the importance of de-escalation of antibiotics in sepsis

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Antibiotics Save Lives

Kumar et al.

Crit

Care Med 2006 Vol. 34, No. 6

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“Each hour of delay in antimicrobial administration [in severe sepsis] was associated with an average decrease in survival of 7.6%”

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What does CMS/ Surviving Sepsis say?

Intensive Care Med (2017) 43:304–377

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Challenges with Recommendations

No consistent definition of time “zero” Overly broad use of broad spectrum antibiotics due to need to meet 1 hour or 3 hour metric Appropriate labs including blood cultures should be drawn prior to the initiation of antibiotics

Clinical Infectious Diseases® 2018;66(10):1631–5

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Barriers to Timely Antibiotic Administration

Delayed antibiotic

People

Methods

Choosing IV Fluids over Abx

Lack of use of sepsis order set

Code Sepsis team not

Available at UMass

Inability to recognize

Sepsis in a timely manner

Complicated system of handoffs

Certain antibiotic may not be available in PYXIS

Issue identifying correct provider/Treatment team

Lack of communication

between RN and MD

Delay in obtaining blood

cultures

Environment

Materials

Lack of STAT antibiotics orders

Medical stepdown unit not available

Order set cumbersome to use

Indication for Abx not clearly stated as sepsis in order

Lack of urgency/knowledge about sepsis bundles

Incomplete Handoff to

Night float or ICU teams

Oder verification process is different on floors

No sepsis BPA in EPIC

IV Pump module not available

Courtesy of Meghna Trivedi MD

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Provider recognizes sepsis

Antibiotics ordered STAT

RN receives and acknowledges order

Pharmacy workflow

Nursing workflow

Establishes IV access

Awaits blood

cutures

before starting Abx

Orders IV Module in EPIC to administer Antibiotic (

STAT order takes less than 10 minutes to arrive

)

Antibiotics administered to patient

Order prioritized in pharmacy verification queue

Antibiotic verified by pharmacist

Antibiotic is dispensed

within 30 minutes

RN gets Antibiotic

Abx available in Pyxis

Tech runs it up to the floor

Abx tubed up to the floor

60

minutes

Courtesy of Meghna Trivedi MD

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Time to Antibiotics

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Impact of Algorithms/ Guidelines

Reduce hospital mortalitypre-order set 48.3% vs post-orderset 35% p=0.139 Reduce 28 day mortality

pre-order set 48.3% vs. post-orderset 30% p=0.040Improved survival OR 0.77 (0.67-0.89) Reduced length of stay OR 0.81 (0.70-0.94)It is important to include education to increase the use and understanding of order sets.

Crit

Care Med 2006 Vol. 34, No. 11

Nsutebu

 EF, et al. Postgrad Med J 2018;94:463–468

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Improve Organism Detection

Blood cultures should be collected prior to initiation of antibiotic therapy to ensure the greatest likelihood of identifying a pathogen

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Antibiotics in Ordersets

Should be based upon likely source of infection

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Antibiotic Choice

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Pathogen Specific Recommendations

Pathogen

Recommendation/Observation

Streptococcus pneumoniae

Penicillin G and Ceftriaxone

Staph aureus

MSSA: Cefazolin

MRSA: Vancomycin

Enterococcus

1

st

line: Ampicillin

2

nd

line: Vancomycin

Pseudomonas aeruginosa

Piperacillin/Tazobactam

Add on agent: Tobramycin

Escherichia coli

Ceftriaxone

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Empiric Antibiotic Recommendations

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Risk Factors for MDRO/Health Care Associated Pathogens

IV broad spectrum antibiotics within 90 daysHistory of MDRO Local high antibiotic resistance ratesChronic dialysis within 30 daysRenal replacement therapy with last 30 days Home wound careMechanical ventilation greater than 5 days

Immunosuppression (HIV/AIDS, hematologic cancer, solid cancers on chemotherapy, corticosteroids, treatment with immunosuppressive drugs, etc.). Central venous catheter Hospitalization greater than 5 daysResidence in a LTAC

Clinical Infectious Diseases

,2016; 63: 61–e111, 

Clinical Infectious Diseases 2017;65: 1607-1614

Infect Control Hosp Epidemiol

 2017;38:266–272

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Need for combination therapy?

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Combination Therapy

When to use two agents?

Two agents active gram negatives are preferred in septic shockIncrease the likelihood of having one active agent Especially in patients with risk factors for resistance pathogens After susceptibilities are known, monotherapy can be used Reduced side effects

Combination Therapy Definition

Utilizing two antibiotics of different antimicrobial classes to treat a pathogen

Has not been shown to be more effective at eradicating or eliminating infection

Clinical Infectious Diseases® 2018;66(10):1631–5

Pseudomonas Susceptibility:

Pip/

tazo

= 81%

Tobramycin 93%

Adding Tobramycin adds 12% more coverage

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How do you optimize it?

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PKPD Optimization

“We recommend that dosing strategies of antimicrobials be optimized based on accepted pharmacokinetic/pharmacodynamic principles and specific drug properties in patients with sepsis or septic shock.” – Sepsis Guidelines 2016

Lancet Infect Dis

2014; 14: 498–509

Critical Care (2018) 22:23

3

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Principles of Pharmacodynamics

Time

Dose

Time> MIC

Peak/MIC

AUC/MIC

MIC

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Pharmacokinetics/Pharmacodynamics MIC- Minimum Inhibitory Concentration The lowest required concentration to inhibit growth

Specific to each antibiotic and organism

SusceptibleIntermediateResistant

Organism

can be eradicated

Requires higher doses or concentratio

n to achieve efficacy

Less

than optimal results

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Beta-Lactams in Sepsis

First Dose should always be administered as a bolus (30 minute infusion)Improved mortality in patients receiving continuous or prolonged infusionsAntibiotics with prolonged infusions:

Cefepime Meropenem Piperacillin/Tazobactam

Intensive Care Med (2016) 42:1535–1545

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Prolonged Infusion

Cefepime over 3 to 4 hours Increase Time above the MICAble to achieve higher MIC

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Apr. 2009, p. 1476–1481

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Aminoglycoside Pharmacokinetics in Septic Shock

Intensive Care Med (2002) 28:936–942

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Clinicalgate.com

Vancomycin Pharmacokinetics

“

In seriously ill patients, a loading dose of 25-30 mg/kg (based upon actual body weight) can be sued to facilitate rapid attainment of target trough serum vancomycin concentrations.”

– ASHP Therapeutic Monitoring of Vancomycin Position Statement

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Which agent do you give first?

Beta-lactams are the most active agents in sepsis and should be administered first

Antibiotics can be administered together

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What are molecular diagnostics?

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Standard Culture Timeline

0 HR

Culture collected

1-2 HR

Cultures planted on agars

and incubated

18-24 HR

Cultures are read for growth

and are set up on automated system

24 HR

Organisms Identified

and Reported

48 HR

Susceptibilities reported

Start Empiric Therapy

Adjust to Directed Therapy

E.coli

Ampicllin

R

Ceftriaxone R

Cefepime S

Gentamicin S

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Rapid Diagnostics Timeline

0 HR

Culture Collected

1-2 HR

Culture set up on molecular

8 HR

Organism Identified w/ mechanism of resistance

18-24 HR

Cultures are set up on automated system

48 HR

Susceptibilities reported

Empiric Antibiotics Started

Directed Antibiotic Therapy

E.Coli

w/ CTX- M

Ampicllin

R

Ceftriaxone R

Cefepime S

Gentamicin S

1-2 HR

Cultures planted on agars

and incubated

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Minimize Adverse Events

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De-escalation

Benefits

Reduce adverse events

Reduced resistance organisms (collateral damage)

Reduce Cost

Increased survival

Risk

Missing pathogens

Unlikely to be accomplished in patients not adequately covered initially

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De-escalation Reduces Mortality in Severe Sepsis and Septic Shock

Intensive Care Med (2014) 40:32–40

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Adverse Events

Increase multi-drug resistant organisms with longer courses of therapy Increase risk of acute kidney injury with longer courses of vancomycin + piperacillin/tazobactam

Clinical Infectious Diseases® 2017;64(2):116–23

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Objectives

Identify the role of antibiotics in sepsisAntibiotics reduce mortality when given early in sepsisDescribe the challenges to timely antibiotic administrationsHard to identify time zero

Not using STAT on antibiotics ordersLack of communication between team membersList 3 ways to optimize antibiotics in sepsis Administer beta-lactams as prolonged infusionsAdminister aminoglycosides at higher doses Administer compatible antibiotics at the same time if line access allows

Understand the importance of de-escalation of antibiotics in sepsis

Reduce adverse events (AKI)

Improved survival

Reduce length of hospital stay

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Antimicrobial Stewardship

Select antibiotics based upon national guidelines and local susceptibilities

Patient specific factors (immunosuppression, indwelling catheters, allergies)

Common pathogens for suspected source

Daily review of clinical signs and symptoms of infection

Review of cultures and molecular diagnostics

Analy

ze current dosing strategy

Narrow therapy based upon cultures and to minimize adverse events

Consider shorter durations based upon clinical status

De-escalate

Evaluate

Initiate

Optimization

Utilize pharmacokinetic/ pharmacodynamic principles to increase cidality

J Intensive Care Med.

 2018 Jan 1

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Antibiotic Use in Sepsis and Stewardship

Maureen Campion, PharmDClinical Pharmacy Specialist- Infectious DiseaseUMass Memorial Medical Center