Maureen Campion PharmD Clinical Pharmacy Specialist Infectious Disease UMass Memorial Medical Center Disclosure statement I have no actual or potential conflict of interest in relation to this programpresentation ID: 908363
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Slide1
Antibiotic Use in Sepsis and Stewardship
Maureen Campion, PharmDClinical Pharmacy Specialist- Infectious DiseaseUMass Memorial Medical Center
Slide2Disclosure statement
I have no actual or potential conflict of interest in relation to this program/presentation.
Slide3Objectives
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
Slide4Antibiotics Save Lives
Kumar et al.
Crit
Care Med 2006 Vol. 34, No. 6
Slide5“Each hour of delay in antimicrobial administration [in severe sepsis] was associated with an average decrease in survival of 7.6%”
Slide6What does CMS/ Surviving Sepsis say?
Intensive Care Med (2017) 43:304–377
Slide7Challenges 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
Slide8Barriers 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
Slide9Provider 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
Slide10Time to Antibiotics
Slide11Impact 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
Slide12Improve Organism Detection
Blood cultures should be collected prior to initiation of antibiotic therapy to ensure the greatest likelihood of identifying a pathogen
Slide13Antibiotics in Ordersets
Should be based upon likely source of infection
Slide14Antibiotic Choice
Slide15Pathogen 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
Slide16Empiric Antibiotic Recommendations
Slide17Risk 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
Slide18Need for combination therapy?
Slide19Combination 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
Slide20How do you optimize it?
Slide21PKPD 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
Slide22Principles of Pharmacodynamics
Time
Dose
Time> MIC
Peak/MIC
AUC/MIC
MIC
Slide23Pharmacokinetics/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
Slide24Slide25Beta-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
Slide26Prolonged 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
Slide27Slide28Aminoglycoside Pharmacokinetics in Septic Shock
Intensive Care Med (2002) 28:936–942
Slide29Slide30Clinicalgate.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
Slide31Which agent do you give first?
Beta-lactams are the most active agents in sepsis and should be administered first
Antibiotics can be administered together
Slide32What are molecular diagnostics?
Slide33Standard 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
Slide34Rapid 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
Slide35Minimize Adverse Events
Slide36De-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
Slide37De-escalation Reduces Mortality in Severe Sepsis and Septic Shock
Intensive Care Med (2014) 40:32–40
Slide38Adverse 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
Slide39Objectives
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
Slide40Antimicrobial 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
Slide41Antibiotic Use in Sepsis and Stewardship
Maureen Campion, PharmDClinical Pharmacy Specialist- Infectious DiseaseUMass Memorial Medical Center